\r\n\t
\r\n\tSince they involve very small amounts of energy, high sound pressure levels are increasingly simpler and cheaper to emit. Noise is everywhere - it can be emitted as an energy waste by traffic or factories, but also by teenagers looking for loneliness in an overpopulated world.
\r\n\t
\r\n\tWhen the noise emission ends, it will not be possible to find its footprint in the environment, hence it is necessary to be in the right place at the right time to measure it. Moreover, having adequate instruments, updated protocols and trained personnel are mandatory to achieve that. Even then, decision makers must clearly understand the reported situation to decide the need and importance of taking further actions.
\r\n\t
\r\n\tThis book will address issues of noise in the city, in the neighborhood or at work, aspects about management and consequences of exposure to high sound pressure levels ranging from the auditory, extra-auditory and psychophysics effects to the addiction to noise and the loss of solidarity.
\r\n\t
\r\n\tThe book aims to provide a various points of view and analysis of cases regarding this omnipresent pollutant.
Salicylic acid (SA) in plants is a ubiquitous compound shown to be pivotal in initiating the response to a variety of physical, chemical and biological insults [1]. Analgesic and antipyretic properties of plant extracts, notably from willow, meadowsweet and myrtle, had been known for many centuries before isolation of SA as the active principle. Since synthesis of its acetyl ester—aspirin—investigation has focused on the properties of that compound which is rapidly hydrolysed (serum t\n1/2 of 20 min) to SA which itself has a half-life of 2–4 h [2]. The demonstration that aspirin works by serine side chain acetylation of Cox-1 and Cox-2 isoforms has detracted attention from SA itself; that compound, despite weak reversible Cox 1 and absent Cox 2 inhibition, is as effective as aspirin in vivo in suppressing inflammation [3]. Inhibition of transcription of the Cox-2 gene by micromolar concentrations of SA is the likely explanation [4].
\nInvestigating the possible use of low dose aspirin as an aromatic probe to measure hydroxyl free radicals by assessing the hydroxylation of SA to form 2,3 and 2,5 dihydroxybenzoic acids (DHBAs)—Figure 1—required a sensitive HPLC assay with appropriate controls. That work revealed the presence of substances which had identical retention times to SA, 2,3 DHBA and 2,5 DHBA in the serum extracts of subjects not taking aspirin. The exclusion of contamination was followed by studies to determine the authenticity of these substances as SA, 2,3 DHBA and 2,5 DHBA.
\nMetabolism of aspirin, salicylic acid and benzoic acid. (1) acetylsalicylic acid (aspirin); (2) salicylic acid; (3) salicyluric acid; (4) 2,5 dihydroxybenzoic acid; (5) 2,3 dihydroxybenzoic acid; (6) 2,3,5 trihydroxybenzoic acid; (7) benzoic acid; and (8) hippuric acid.
Examination of the chromatograms of blank serum or plasma from published methods of SA analysis revealed the presence of an unknown substance with a retention time (Rt) similar to SA [5, 6]. While Ruffin et al. [7] reported SA in the plasma from 17 of 53 subjects at baseline there was no information as to how they confirmed identification of the compound.
\nWe examined samples from drug free volunteers: extracts of acidified serum were analysed by high performance liquid chromatography (HPLC) with electrochemical detection. Chromatographic conditions were altered and the Rts of the unknown compounds compared against authentic SA, 2,3 DHBA and 2,5 DHBA. Serum samples (some spiked with SA) were also incubated with a bacterial salicylate hydroxylase and the substance which had a Rt identical to SA disappeared. Finally the trimethylsilyl (TMS) derivative of the unknown and SA had, using gas chromatography–mass spectrometry (GC–MS), a similar retention time and total ion chromatogram [8].
\nArmstrong et al. [9] had detected, by paper chromatography, a compound with characteristics similar to those of SU in the urine of 400 people who had not taken salicylate drugs. That was in an admixture of 49 compounds of predominantly, it was suggested, dietary origin. Von Studnitz and colleagues, who also used a paper system, suggested SA might be one of the phenolic acids in the urine of subjects on a diet restricted to glucose and citric acid [10]. Young reported a compound with thin layer chromatographic properties of SU [11] in a single individual on a synthetic diet, while Finnie and co-workers found a similar compound on their paper system in children not taking salicylate drugs [12]. At the time of all these earlier investigations methods for adequately characterising and quantifying the purported SA and SU were not readily available.
\nOther work [13] designed to assess the dietary importance of salicylates had examined acid-treated urine using HPLC with fluorescence detection but salicylates other than SA, salicylate precursors and structurally related compounds may have been included in the values reported.
\nWe examined 24 h urine samples from 10 volunteers who had not taken any salicylate drugs during the previous 2 weeks. The acid hydrophobic compounds (=organic acids) were separated using HPLC and quantified electrochemically. The Rts of the extracted substances and those of SA and SU were compared under two sets of chromatographic conditions and found very similar to those of authentic substances. The unknown substances, isolated by HPLC, and treated with acetyl chloride in methanol were compared with the methyl esters of SA and SU using GC–MS. After esterification the unknown compounds had mass spectra and Rts comparable to those of methyl-SA and methyl-SU [14].
\nThese findings in serum and urine led us on to explore, in some detail, the likely dietary sources for the salicylate compounds we found and confirmed. At the time interest was re-awakening in the potential benefits of salicylates commonly found in the diet [13]—as opposed to what were considered traditional plant medicine sources.
\nThe occurrence of “natural salicylates”, such as SA, in strawberries and other fruits was raised in the Lancet in 1903 [15] and the matter of whether these natural salicylates were superior to synthetic salicylates was the subject of a JAMA editorial in 1913 [16]—no superiority was concluded! Interest then appeared to wane until re-invigorated by the popularity, from ∼1970, in therapeutic trials—arising from the apparent cross-reactivity of tartrazine and aspirin—of exclusion diets.
\nMany plant derived non-nutritive compounds exert, in mammalian systems, biological activities that may have an impact on health and disease risk [17] and we proposed [18] that SA might provide a link between aspirin, diet and the prevention of colorectal cancer (CRC). There is good evidence that the regular intake of aspirin decreases the risk of developing cancer [19]. A mechanism for platelet mediated CRC tumorigenesis has been proposed [20]; that would, of course not be attributable to SA itself but a more balanced view is that both constituent groups of aspirin (acetyl and SA moieties) contribute to the anti-cancer effects [21].
\nAssessment of the extent of the contribution of diet to SA in blood and urine cannot be easily inferred from direct analysis of its concentration therein. There is considerable variability in peak serum levels of SA in subjects receiving a standard dose [7] while urinary salicylate is influenced by urine flow, pH, the presence of other organic acids and the saturability of SU formation and/or excretion [2].
\nIt was unclear whether sufficient salicylic acid could be obtained from dietary sources to influence health and disease with estimated daily intakes ranging from 0.4 to 200 mg/day [13, 22, 23]. That range reflected the disparate information available on the salicylate content of foods.
\nComparison, in the serum of subjects not taking aspirin, of SA levels in 37 vegetarians and 39 non-vegetarians found higher concentrations in the former [24]. That study revealed median concentrations of 0.11 (range 0.04–2.47) μmol/L and 0.07 (range 0.02–0.20) μmol/L respectively: the median of the difference was 0.05 μmol/L (95% confidence interval for difference 0.03–0.08; p < 0.0001). The median SA level measured in serum from 14 patients on aspirin 75 mg/day was, at 10.03 (range 0.23–25.40) μmol/L, significantly higher. However there was overlap in serum SA concentrations between the vegetarians (8 higher than lowest low dose aspirin) and patients taking aspirin (6 below the highest vegetarian value). These findings should be considered in light of the inhibition of COX2 transcription that has been shown to occur at SA levels as low as 0.1 μmol/L [4].
\nIn a further study the urinary excretion of SA and SU was assessed in 24 h samples from 27 non-vegetarians, 21 vegetarians and 40 patients taking 75 or 150 mg aspirin/day [25]. For SU, the principle urinary salicylate, vegetarians excreted significantly more than the non-vegetarians (median 11.01; range 4.98–26.60 μmol/24 h compared with 3.91; range 0.87–12.23 μmol/24 h) but these amounts were significantly lower than those excreted by patients on aspirin. Significantly more SA was excreted by the vegetarians (median 1.19; range 0.02–3.55 μmol/24 h) than by the non-vegetarians (median 0.31; range 0.01–2.01 μmol/24 h). The median amounts of SA excreted by the vegetarians and the patients taking aspirin were not significantly different. These values were comparable to those found earlier, using less specific methodology, in a group of drug free volunteers on a variety of diets [13].
\nAwareness that certain spices had been reported [22] to contain especially high concentrations of SA and the reported very low incidence of colorectal cancer in rural India [26] led to our particular assessment of spices.
\nSpices, Indian cooked dishes and blood and urine samples taken after ingestion of a test meal were investigated for their salicylate content. Total salicylate content determination required a preliminary alkali treatment step before our standard extraction [27] as, in plants, phenolic glycosides and carboxylic esters are present as well as the “free” phenolic acid. Our standard assay conditions for SA were then applied. All samples of spices and cooked meals examined contained SA (up to 1.5 wt%); cumin, turmeric, red chilli powder, paprika and cinnamon were especially rich sources. Our measurements were considerably higher than those previously published [22]. That was attributed to previously suboptimal extraction, chromatographic separation and detection [27]. The identity of the SA fractions (on HPLC) from cumin, paprika and turmeric was confirmed, after elution and esterification, by GC–MS of their methyl esters.
\nThe potential bioavailability of SA derived from a prepared meal was assessed in a single aspirin free volunteer after a 10 h fast. Consumption of 545.3 g of a cooked vegetable dish (shown by aliquot assay to contain 94.03 g of total salicylates) was followed by regular blood and urine collection over 6 h. Serum SA doubled within 1.5 h and urinary SU increased ∼20-fold during that time.
\nNative Indian volunteers, living in a rural area near Chennai, had been recruited for another study as representative of that community for health lifestyle and nutritional status. They had a diet of locally grown vegetables, grains and pulses flavoured with spices and herbs. The serum from these 21 South Indians had a median SA concentration of 0.263 μmol/L (range 0.05–0.64—significantly higher (∼2.5- to 3.5-fold higher) than those found in the sera of the other groups reported above [24]; p < 0.001 against both vegetarians and non-vegetarians by Mann–Whitney U test) [27]. Summarised and compared with other results below in Table 1.
\n\n | Median (μmol/L) | \nRange (μmol/L) | \n
---|---|---|
Vegetarians n = 37 | \n0.110 | \n0.04–2.47 | \n
Non-vegetarians n = 39 | \n0.070 | \n0.02–2.00 | \n
Southern Indian villagers n = 21 | \n0.263 | \n0.05–0.64 | \n
75 mg aspirin takers n = 14 | \n10.03 | \n0.23–25.4 | \n
Given that SA is a stress hormone in plants we can anticipate that locality, varietal and growing conditions could affect total salicylate content at harvesting before any variability in processing conditions and storage effects. Wide reported ranges for different brands assayed using standard conditions are therefore not particularly surprising. For example the SA content of five brands of orange juice obtained from Scottish retailers ranged from 0.47 to 3.01 mg/kg [29].
\nUsually an open question but, given the above considerations, probably not in respect of SA content. Thus the median SA contents in organic and non-organic vegetable soups were 117 ng/g (range 8–1040) and 20 ng/g (range 0–248) respectively; the median between the difference groups was 59 ng/g (95% confidence intervals 18–117 ng/g), p = 0.032 by Mann Whitney U test [30]. Consider also constraints of drought, other physical stresses and non-availability of pest control which inevitably prevail in many emergent nations.
\nClearly sample selection and methodology will affect estimates of SA content in the diet. Using the assay methodology our group developed [27, 30] to supplement published results, Wood et al. [29] prepared a comprehensive dietary database. They filtered published results of dietary constituent total salicylate content by specific criteria. Food items had to be randomly selected and purchased from various commercial outlets at different times of the year; food samples to be prepared using standard domestic practices; optimised sample extraction and hydrolysis conditions were to be clearly described or cited, and salicylate determination to be based on modern techniques of HPLC and mass spectrometry with validation and quality assurance methods summarised. Combination of such published data, which met these criteria, together with their in-house analyses resulted in a database of 27 types of fruit, 21 vegetables, 28 herbs, spices and condiments, 2 soups and 11 beverages—expressed as median values to reflect the non-normal distribution of the results.
\nSubsequently dietary intake was assessed by applying this salicylate database, using a validated questionnaire, to 237 healthy individuals age range (17–72) from Aberdeen [29]. Estimated median total salicylate intakes for men and women were 4.42 and 3.16 mg/day respectively, a gender difference not sustained when corrected for energy. Primary food sources of salicylates as shown in Figure 2 were alcoholic beverages (22%), herbs and spices (17%), fruits (16%), non-alcoholic beverages including fruit juice (13%), tomato-based sauces (12%) and vegetables (9%). Salicylate intake was significantly (p < 0.001) and positively associated with intakes of fibre, potassium, vitamin C and alcohol!
\nRelative contributions of different food groups to total salicylate intake of a Scottish population. Source: [29].
There were clear suggestions in the literature that SA and SU in urine might not all derive from diet, given their presence in the urine of subjects on restricted diets [9, 11]. In addition quantification of the contribution from fruit and vegetable consumption to circulating SA levels in man had demonstrated, using a sensitive and specific method that <20% of the variability derived from these sources [31]. So some circulating SA in aspirin-naïve or -free individuals may derive from other dietary sources or be of non-dietetic origin.
\nBlood samples, serum or plasma, were obtained from animals at London Zoo or the Department of Biological Services, University of Glasgow in accordance with their approved codes of practice. The results (Table 2) showed that species regarded as primarily carnivorous had blood SA levels comparable to those measured in herbivores [28]. The highest levels detected were in the range associated with aspirin use in man and only the crustacean body fluid samples examined did not contain SA.
\nAnimal | \nPhylogenetic class | \nSA (μmol/L) | \n
---|---|---|
Burrowing Owl | \nAves | \n9.854 | \n
Ne-Ne | \nAves | \n5.609 | \n
Indian Rhinoceros | \nMammalia | \n4.700 | \n
Pigmy Hippopotamus | \nMammalia | \n2.384 | \n
Agouti | \nMammalia | \n2.116 | \n
Asian Elephant | \nMammalia | \n1.635 | \n
Burmese Python | \nReptilia | \n1.362 | \n
Rabbit | \nMammalia | \n1.129 | \n
Piglet | \nMammalia | \n1.010 | \n
Arabian Onyx | \nMammalia | \n0.777 | \n
Sheep | \nMammalia | \n0.715 | \n
Tiger\na\n\n | \nMammalia | \n0.661 | \n
Brown Trout | \nPisces | \n0.538 | \n
Giraffe | \nMammalia | \n0.507 | \n
Donkey | \nMammalia | \n0.473 | \n
Sacred Ibis | \nAves | \n0.353 | \n
Goat | \nMammalia | \n0.310 | \n
Giant Anteater | \nMammalia | \n0.293 | \n
Collared Peccary | \nReptilia | \n0.237 | \n
African Lion\na\n\n | \nMammalia | \n0.226 | \n
Cow | \nMammalia | \n0.216 | \n
Gelada Baboon | \nMammalia | \n0.210 | \n
Chinese Alligator | \nMammalia | \n0.156 | \n
Domestic Cat | \nMammalia | \n0.144 | \n
Pond Heron | \nAves | \n0.136 | \n
Gorilla | \nMammalia | \n0.125 | \n
Monkey*\n | \nMammalia | \n0.080 | \n
Mouse | \nMammalia | \n0.078 | \n
Rat | \nMammalia | \n0.069 | \n
Domestic Cat**\n | \nMammalia | \n0.058 | \n
Chimpanzee | \nMammalia | \n0.033 | \n
Crab***\n | \nCrustacea | \n<0.005 | \n
Prawn | \nCrustacea | \n<0.005 | \n
Concentration of salicylic acid (SA) in the blood or body fluid of a variety of animals.
Mean concentration in five animals.
Red faced spider monkey.
Fed only meat.
European shore crab.
As some bacteria, notably Mycobacterial, Yersinia and Pseudomonas species, synthesise SA to enhance iron chelation (see Section 5.1) the possibility of a gastrointestinal particularly colonic, bacterial source for SA was assessed in two animal models. Pooled serum from six mice treated with neomycin 100 mg/kg/day for 4 days had a serum SA concentration which was, at 0.309 μmol/L, slightly higher than the level of 0.268 μmol/L measured in six untreated animals. Other measurements were done on serum samples from Sprague-Dawley rats delivered by caesarean section, raised in a sterile environment and fed sterilised food. A group of 8 such germ free animals had a pooled serum SA level which was, at 0.166 μmol/L, ∼2.5× greater than the level of 0.069 μmol/L in serum from a group of control animals [28].
\nA preliminary study followed serum SA and urinary SA + SU over 3 days on a water/milk diet (confirmed salicylate free on analysis) in a subject free of aspirin for at least 2 weeks. Excretion of SA + SU continued at a rate of ∼2.1 μmol/24 h throughout and serum SA did not fall—over the 72 h of the study—below 0.1 μmol/L (20× the limit of detection of the assay) [28].
\nIn six patients who had total colectomy or rectal excision following standard pre-operative bowel preparation low level serum SA (range 0.012–0.085 μmol/L) was detected and urinary SA + SU excretion persisted (median lowest level 0.613 μmol/24 h; range 0.184–7.607) in all subjects for up to 5 days postoperatively, rising only on refeeding [28]. These results also, of course, have some relevance to Section 4.2.
\nBenzoic acid (BA) is a natural constituent of plants, with high levels found in fruits and vegetables. In plants synthesis of SA derives—at least partially—from phenylalanine via cinnamic and benzoic acids. Prior work, using formula diet feeding, also demonstrated that hippuric acid, the main metabolite of BA, may be formed endogenously in man, while a Sprague-Dawley rat radiolabeled experiment showed phenylalanine as the likely precursor [32]. Sodium benzoate as a food preservative also contributes to human intake and very high doses have been used in hepatic encephalopathy. These considerations led us to determine whether addition of BA to a very carefully standardised diet produced any change in serum or urinary salicylates—see Figure 1.
\nA preliminary study, over 4 days in two subjects, suggested that BA, 1 or 2 g/day on days 3 and 4 might be associated with a modest increase in urinary SA + SU excretion. Subsequently a labelled study was undertaken over 3 days in six individuals (4 M, 2F) who received 1 g of uniformly ring-labelled 13C BA with each of their main meals on day 2. They replicated their carefully recorded day 1 diet throughout and had regular blood sampling with complete urine collections. The total SA + SU urinary excretion increased, but not significantly (p = 0.052) and only in the 8–16 h sample after the first dose of BA. While no 13C was detected in samples prior to ingestion of the BA, the 13C isotope was confirmed in the 8–16 h urine sample from all six subjects. Its presence was determined by preliminary GC fractionation before subjecting the relevant fractions to derivatization and GC–MS. The 13C isotope accounted, by selective ion monitoring, for 0.4–10.9% (median 3.4%) in the SA derivative and 6.8–43.1% (median 33.9%) in the SU derivative. In addition considerable amounts of the expected 13C6-labelled hippuric acid were found [28]. Set against the total SA + SU levels the extent of the SU 13C6 labelling found might be considered surprising but could, as well as confirming the in vivo synthesis of SA, point to possible bioregulation of the levels of endogenous serum SA.
\nThe protean actions of aspirin in animals and man are here, in a short review by JRL an GJB, set against what is known of the role of its SA precursor in earlier life forms.
\nThis complex area is here only briefly overviewed in relation to its potential for pointing to possible effects of SA preserved into animals.
\nPara-aminosalicylic acid (PAS), the earliest truly effective anti-tuberculous agent, was long thought an analogue for para-aminobenzoic acid and so an inhibitor of folic acid biosynthesis. That was before the discovery of the mycobacterial siderophore (iron binding molecule) mycobactin, and that SA (also formed, as an extracellular metabolite, by mycobacteria in iron deficient conditions) is its direct precursor. It appears PAS primarily inhibits the conversion of SA into myobactin. Possible secondary roles for SA are the transfer of Fe2+ across the cell membrane, either for direct incorporation into various porphyrins and apoproteins, or for storage of iron within the cytoplasm in bacterioferritin (both roles also potential targets for PAS) [33].
\nThere are many kinds of bacterial siderophores but SA or one of its hydroxylated metabolites (2,3DHBA) are at the core of the aryl- capped molecules found in E. coli (Enterobactin); Yersinia sp. and Klebsiella pneumoniae (Yersinibactin); Pseudomonas sp.(Pyochelin); Vibrio sp. (Vibriobactin/Vulnibactin) and Acinetobacter baumanii (Acinetobactin) [34]. These authors described a probe for the initial aryl acid activation enzymatic step in the synthetic pathways of these “bactins” (via a non-ribosomal peptide synthetase pathway initiated by adenylation) and suggested lack of human homologues makes this a potential drug target—but see Section 5.3.4.
\nIntriguingly investigation into the bioinorganic chemistry of bacterial siderophores has revealed that many have functional capacities other than mere iron homeostasis. Examples include interactions with other metals such as zinc, copper and boron; signalling agents (referred to as “ferrimones”) in the regulation of genes related to iron metabolism; protection—by those with catecholate structures—from oxidative stress and an antibiotic function in sideromycins [35].
\nFinally bacterial growth in the presence of salicylate can be both beneficial and detrimental. On the one hand an intrinsic multiple antibiotic resistance phenotype can be induced and on the other reduced resistance to some antibiotics might result and bacterial virulence factors may be affected [36]. While the in vivo consequences of these observations is speculative the findings highlight, the authors suggest, the ability of salicylate to alter gene expression; they claim that the only life form not yet (then) shown to be affected by salicylate is the Archaea!
\nWhile salicylic acid (initially from plant sources) has been used in therapeutics for millennia detailed knowledge of its role in plants is relatively recent. Although plant phenolics are diverse and ubiquitous they were traditionally assumed to be unimportant secondary metabolites but SA in plants is a critical hormone playing a direct role in the regulation of many aspects of growth and development as well as in thermogenesis and disease resistance [37]. The first clear evidence came, intriguingly (in relation to its antipyretic qualities in animals), from its role in voodoo lily thermogenesis; that appears to be mediated by stimulation of the mitochondrial alternative respiratory pathway [38]. Soon thereafter its role as a defence signalling hormone was documented—though the ability of plants to develop acquired immunity after pathogen infection was first proposed many years earlier. In the acquired immunity—called “systemic acquired resistance” (SAR)—of plants to biotrophic (i.e. threatening living cells) pathogens, the role of SA is pivotal. Careful study has identified two pathways for its synthesis, numerous proteins that regulate its synthesis and metabolism and some signalling components, including a large number of potential targets/receptors, which operate downstream of SA [39]. This is a perplexing field; for example while the non-specialist can readily appreciate methylation of SA to a volatile ester for transport through the phloem (before demethylation at a site where SA levels are low) subsequent steps are complex. As these authors point out it is increasingly evident that SA does not signal immune response by itself but as part of an intricate network of other plant hormones. We would highlight, from the viewpoint of the present review, their suggestion that it is important to differentiate SA “targets” from the subset (whose criteria, they concede, will be difficult to specify) that meet additional conditions to be designated “receptors” [40]. That idea is particularly relevant when later considering the propensity of aspirin to acetylate many animal protein “receptors”—see Section 5.3.4.
\nThe wide range of basal SA levels between and within plant species, and potential for a biphasic/concentration dependent response may explain some conflicting reports on the spectrum of plant processes it influences. Despite these caveats the long list affected by exogenous SA includes resistance to biotic (pathogen-associated) stress and tolerance to many abiotic stresses (drought, chilling, heat, metal, UV radiation, and salinity/osmotic stress) as well as multiple aspects of plant growth and development. These include photosynthesis, senescence, thermogenesis, respiration, glycolysis, the Krebs cycle and the alternative respiratory pathway [40].
\nAlthough the use of willow extracts had been known for centuries the report of its first well documented use—as a cheaper remedy for “the agues” than expensive cinchona bark—focused on its antipyretic properties. Then, particularly in the decades following the isolation of SA as the active principle, evidence steadily accrued for its efficacy as an analgesic and anti-inflammatory in e.g. acute rheumatic fever.
\nFollowing Hoffman’s synthesis of the apparently better tolerated ester in 1897 use of that compound prevailed. ASA was the prototype non-steroidal anti-inflammatory drug (NSAID); it seems that term arose from a need to distinguish it from the undesirable effects of synthetic steroids. As a prodrug for a long recognised active agent its mode of action was naturally linked to the effects of SA.
\nIt was not until the 1960s that work by Vane and Piper led to the proposal of a single mode of action of ASA in the inhibition of prostaglandin synthesis. The resulting paradigm-shifting series of experiments led to the discovery that inhibition of constitutive COX-1 and of COX-2 (predominantly inducible) by serine side-chain acetylation altered levels of prostaglandins and leukotrienes. This revelation came at a time when the potency of ASA as an inhibitor of platelet aggregation in the treatment of vascular disease was coming to the fore. So Vane’s work explained, in a unitary and coherent way, the multiple pharmacological actions of ASA. The ester prevailed—particularly as SA itself had no significant anti-COX-1 effect on platelets.
\nThis emphasis arose from the apparent efficacy, in cancer chemo-protection, of ASA at the low doses (∼70–100 mg/day) used to inhibit platelet aggregation. Irreversible inhibition of COX-1 in the circulating anucleate platelets ensures that thromboxane A2 formation is prevented throughout their lifespan without, at these doses, suppressing the production of prostacyclin (PGI2) which mediates platelet inhibition and vasodilatation. While that is the principle effect required in vascular disease platelet activation also triggers a host of processes leading to leucocyte recruitment into various tissues and subsequent phenotypic changes in stromal cells contributing to atherosclerosis, intestinal inflammation and cancer as well as atherothrombosis [41]. That review also encompasses the non-COX effects of the widespread acetylation of other proteins by ASA—quoting one study which revealed over 12,000 ASA-mediated acetylations in over 3700 proteins!
\nThere is a trend to describe non-COX, indeed increasingly non-platelet, effects of ASA as “non-canonical”. That tag appears to include almost all actions not demonstrably due to COX acetylation with the possible exception of inhibition of COX-2 gene transcription [4].
\nWe should, however, remind ourselves that
It is generally accepted that although SA is a much weaker inhibitor of COX activity in vitro their anti-inflammatory effects in vivo are comparable [3].
ASA has a very short serum half-life compared with SA [2]; its passage (almost certainly total salicylates were determined) through the blood/brain barrier is slow and incomplete [42]. That observation is particularly relevant to the oft forgotten central action of salicylates [43].
ASA’s antipyretic effect was first validated centuries ago using plant extracts; it is mainly due to inhibition of COX-2 in the hypothalamus [44].
There is a clear dose/response relationship between the analgesic effect of ASA up to a dose of 1.2 g [45] compared with the plateau above ∼100 mg/day for the effect on platelets and its efficacy in chemoprevention of colorectal adenomas [46].
The eminent facility for ASA to acetylate proteins has been known for decades and proteomic studies—see above—have shown its very marked extent. While the functional relationship between such activity and its effects are unclear the blockade of glucose6phosphate dehydrogenase (G6PD), affecting the pentose phosphate pathway, and disruption of mitochondrial respiration may explain platelet autophagy [41]. Clearly, as for SA in plants, caution is required in the strict definition of ASA receptors [39, 40].
\nWhile the above caveat applies the blunderbuss masking effect of acetylation is not a consideration. At least 15 SA binding proteins are described to date [39] but some intriguing examples point to effects on proteins with plant and bacterial homologues.
\nHuman glyceraldehyde3-phosphate dehydrogenase (HsGADPH)—has been identified as a SA binding protein—as it is in plants. In addition to its central role in glycolysis GADPH participates in pathological processes, with effects on viral replication and neuronal cell death [47]. Its suppression, by low μM levels of salicylate, in a model of cell death comparable to that induced by reactive oxygen species (ROS) was found. The authors postulate that likely due to suppression of HsGADPH nuclear translocation, mirroring the effect of the anti-Parkinsonian drug Deprenyl.
\nThe same group have also shown [39, 48] that SA targets human high mobility group box 1 (HMGB1), an abundant chromatin associated protein, present in all animal cells; fungi and plants have related proteins. Its diverse effects modulate inflammatory processes. HMGB1’s many activities and receptors likely account for its multiple roles in human disease which include sepsis, arthritis, atherosclerotic plaque formation and cancer. The effect of SA on HMGB1 occurs at concentrations far lower than those required to inhibit COX enzyme activity; an effect on COX2 is on synthesis rather than activity.
\nAn example of a bacterial homologue enzyme, found in mice, is responsible for synthesis of 2,5DHBA—the iron binding moiety of a mammalian siderophore [49]; that enzyme is a homologue of bacterial EntA which catalyses 2,3DHBA production during enterobactin biosynthesis (Section 5.1). 2,5DHBA can, of course, also derive from the metabolism of SA or benzoic acid.
\nOther orthologs of a plant SA receptor—NAD(P)-reductase like proteins—have been characterised in the human neuroblastoma SK-N-SH cell line and mouse brain tissue [50]. Their results may point, the authors claim, to the existence of a thermoregulation system that is evolutionary conserved.
\nThe few direct studies to validate the assertion 5.3.2a above compared salsalate (which yields only SA on absorption) with SA, generally at the higher doses used in rheumatic diseases. Given what we know about the distribution and relative inhibition of COX1 and COX2 it’s not surprising that at comparable doses effects were similar with a predictable lower gastrointestinal toxicity of SA [51]. The authors suggested that, when ASA was originally marketed, commercial forces equated taste and tolerability/toxicity! These prominent rheumatologists concluded that “non-acetylated salicylates should be preferred to ASA in rheumatology”. They clearly supported the German proverb:- “Bitter im Mund, gesund im Korper.”
\nWhile the NSAID categorisation originally served to differentiate the side effects of SA and steroids, very early work had shown a CNS effects specific to salicylates. Later studies—stimulated by discovery of the antipyretic/anti-inflammatory actions of the neuropeptide α-melanocyte stimulating hormone (αMSH)—clearly demonstrated peripheral effects of salicylates introduced into the CNS by injection into the lateral ventricle. These experiments showed that CNS doses which had no effect systemically had a marked effect on the mouse model of inflammation used. The effect was restricted to the salicylates; central injection of an anti-inflammatory dose (when given intra-peritoneally) of indomethacin had no effect: neither did intraventricular dexamethasone or prostaglandin E2 [43].
\nMore recent work on peroxisome proliferator-activated receptors (PPARs) has also shown the importance of central nervous system actions. Peroxisomes are oxidative (H2O2 producing) organelles subserving redox regulation and metabolism of very long chain fatty acids. They are abundant in the CNS, where such fatty acids abound and their increase, when required, is receptor mediated. Studies have compared the anti-inflammatory effect of agonists of PPARα and PPARγ (themselves inactive at the site of inflammation) with the effect of dexamethasone and ASA. Only other agonists and ASA (which itself has generally no direct2 PPAR agonist effect) were found to diminish inflammation when given after the inflammatory insult in contrast to the effect of dexamethasone. The conclusion was that PPARα and PPARγ regulate inflammation through a mechanism similar to salicylates and distinct from that ascribed to steroids [53]. The authors postulated that activating PPARs in the CNS could elicit the release of a salicylate-like compound, an endosalicylate, which may subsequently cause the release of a physiological anti-inflammatory substance such as αMSH.
\nThese results on CNS activity point to steroid/NSAID differentiation which is at least partially dependent on how agents influence the anti-inflammatory and immunomodulatory effect of melanocortins (ACTH and MSH).
\nGiven the ever increasing complexity of SA and ASA effects revealed by basic research it seems blinkered to increasingly restrict focus to platelet/COX effects in the biomedical field.
\nWe reiterate our conclusion that ASA is no mere anti-platelet prototype [54]. That is the case, we aver, for most of the protean pathophysiological effects of ASA and not solely in cancer chemoprevention. The evidence summarised here, particularly our demonstration of the in-vivo synthesis of SA, points to it as a truly endogenous molecule in animals and man. Potential “preserved” receptors which have been described are there, we suggest, not simply to deal with ingested SA or other exogenous precursors.
\nThe place of SA in the biosphere overall is, we think, as pivotal as it appears to be in plants. While a unifying hypothesis to explain its many roles is elusive we suspect they all ultimately relate to the need for evolving life to balance its requirements for oxygen and iron [55]. These authors concluded that the sequestration of iron to restrict its reaction with reactive oxygen species (ROS) is one of our major antioxidant defence mechanisms. They particularly emphasise, in that summary, how such sequestration remains critical to our ongoing resistance to bacterial infection.
\nThe huge increase in energy production arising from enzymatic reduction of oxygen enabled evolution of multicellular animal life. While that was an evolutionary milestone ability to use the resulting reactive oxygen species (ROS) for cell signalling and regulation may have been the first true breakthrough in development of complex life [56]. By then SA was already well established and poised to interact (with ROS) as required. In animals its many effects are unlikely to be less complex than the interactions steadily becoming clarified in plants [39]. Many may depend upon the type of intricate relationships which initiate plant systemic acquired resistance (SAR) with an initial SA induced redox change. Subsequent SA concentration sensitive oligomer/monomer transformation permits nuclear translocation of a cytosolic messenger to activate immune-associated genes [40].\n
\nRe-focus on the importance of the SA moiety of ASA should also lead to further evaluation of SA derivatives which are more active than SA itself in interaction with particular “binding protein/receptors” [47, 48]. At a more basic level we have previously pointed out that, particularly to extend its use in prophylaxis, the risk/benefit profile of ASA may be improved with an SA/ASA combined formulation [54].
\nGiven what we have learned on this investigative journey it is somewhat paradoxical that we embarked upon it driven by desire to capitalise on the hydroxylation of ASA as a biomarker of oxidative “stress” in man—see Section 2.
\nDr. John Robert Paterson (1955–2004), our dear friend who initiated and steered this line of research, always—from schooldays onwards—thought of himself as a chemist first and foremost. Through his long and arduous training in pharmacy, medicinal chemistry, medicine, royal college membership and clinical biochemistry he described himself as a chemist. Most of the work summarised herein, including results published after his death, was either planned by him or arose from discussions during his life. Our prime purpose in undertaking this compilation has been to remain true to his vision. We only pray that there are no glaring chemical errors—the fault is entirely ours if there are.
\nWe are grateful to Hannah Mortlock for the preparation of Figure 1.
\nThe authors declare no conflict of interest.
We wish to thank Dumfries and Galloway Health Board for their support over the many years of these studies, especially their Research and Development and Library services.
\nOur work has been supported financially by the Dumfries and Galloway Health Board’s Salicylic Acid Research Endowment Fund.
\nWe have done our utmost to accurately reflect the findings and conclusions of the many authors quoted in Section 5. Profuse apologies if our reflections on their studies appear at variance with their interpretations.
\nResearch methodology is the path through which researchers need to conduct their research. It shows the path through which these researchers formulate their problem and objective and present their result from the data obtained during the study period. This research design and methodology chapter also shows how the research outcome at the end will be obtained in line with meeting the objective of the study. This chapter hence discusses the research methods that were used during the research process. It includes the research methodology of the study from the research strategy to the result dissemination. For emphasis, in this chapter, the author outlines the research strategy, research design, research methodology, the study area, data sources such as primary data sources and secondary data, population consideration and sample size determination such as questionnaires sample size determination and workplace site exposure measurement sample determination, data collection methods like primary data collection methods including workplace site observation data collection and data collection through desk review, data collection through questionnaires, data obtained from experts opinion, workplace site exposure measurement, data collection tools pretest, secondary data collection methods, methods of data analysis used such as quantitative data analysis and qualitative data analysis, data analysis software, the reliability and validity analysis of the quantitative data, reliability of data, reliability analysis, validity, data quality management, inclusion criteria, ethical consideration and dissemination of result and its utilization approaches. In order to satisfy the objectives of the study, a qualitative and quantitative research method is apprehended in general. The study used these mixed strategies because the data were obtained from all aspects of the data source during the study time. Therefore, the purpose of this methodology is to satisfy the research plan and target devised by the researcher.
The research design is intended to provide an appropriate framework for a study. A very significant decision in research design process is the choice to be made regarding research approach since it determines how relevant information for a study will be obtained; however, the research design process involves many interrelated decisions [1].
This study employed a mixed type of methods. The first part of the study consisted of a series of well-structured questionnaires (for management, employee’s representatives, and technician of industries) and semi-structured interviews with key stakeholders (government bodies, ministries, and industries) in participating organizations. The other design used is an interview of employees to know how they feel about safety and health of their workplace, and field observation at the selected industrial sites was undertaken.
Hence, this study employs a descriptive research design to agree on the effects of occupational safety and health management system on employee health, safety, and property damage for selected manufacturing industries. Saunders et al. [2] and Miller [3] say that descriptive research portrays an accurate profile of persons, events, or situations. This design offers to the researchers a profile of described relevant aspects of the phenomena of interest from an individual, organizational, and industry-oriented perspective. Therefore, this research design enabled the researchers to gather data from a wide range of respondents on the impact of safety and health on manufacturing industries in Ethiopia. And this helped in analyzing the response obtained on how it affects the manufacturing industries’ workplace safety and health. The research overall design and flow process are depicted in Figure 1.
Research methods and processes (author design).
To address the key research objectives, this research used both qualitative and quantitative methods and combination of primary and secondary sources. The qualitative data supports the quantitative data analysis and results. The result obtained is triangulated since the researcher utilized the qualitative and quantitative data types in the data analysis. The study area, data sources, and sampling techniques were discussed under this section.
According to Fraenkel and Warren [4] studies, population refers to the complete set of individuals (subjects or events) having common characteristics in which the researcher is interested. The population of the study was determined based on random sampling system. This data collection was conducted from March 07, 2015 to December 10, 2016, from selected manufacturing industries found in Addis Ababa city and around. The manufacturing companies were selected based on their employee number, established year, and the potential accidents prevailing and the manufacturing industry type even though all criterions were difficult to satisfy.
It was obtained from the original source of information. The primary data were more reliable and have more confidence level of decision-making with the trusted analysis having direct intact with occurrence of the events. The primary data sources are industries’ working environment (through observation, pictures, and photograph) and industry employees (management and bottom workers) (interview, questionnaires and discussions).
Desk review has been conducted to collect data from various secondary sources. This includes reports and project documents at each manufacturing sectors (more on medium and large level). Secondary data sources have been obtained from literatures regarding OSH, and the remaining data were from the companies’ manuals, reports, and some management documents which were included under the desk review. Reputable journals, books, different articles, periodicals, proceedings, magazines, newsletters, newspapers, websites, and other sources were considered on the manufacturing industrial sectors. The data also obtained from the existing working documents, manuals, procedures, reports, statistical data, policies, regulations, and standards were taken into account for the review.
In general, for this research study, the desk review has been completed to this end, and it had been polished and modified upon manuals and documents obtained from the selected companies.
The study population consisted of manufacturing industries’ employees in Addis Ababa city and around as there are more representative manufacturing industrial clusters found. To select representative manufacturing industrial sector population, the types of the industries expected were more potential to accidents based on random and purposive sampling considered. The population of data was from textile, leather, metal, chemicals, and food manufacturing industries. A total of 189 sample sizes of industries responded to the questionnaire survey from the priority areas of the government. Random sample sizes and disproportionate methods were used, and 80 from wood, metal, and iron works; 30 from food, beverage, and tobacco products; 50 from leather, textile, and garments; 20 from chemical and chemical products; and 9 from other remaining 9 clusters of manufacturing industries responded.
A simple random sampling and purposive sampling methods were used to select the representative manufacturing industries and respondents for the study. The simple random sampling ensures that each member of the population has an equal chance for the selection or the chance of getting a response which can be more than equal to the chance depending on the data analysis justification. Sample size determination procedure was used to get optimum and reasonable information. In this study, both probability (simple random sampling) and nonprobability (convenience, quota, purposive, and judgmental) sampling methods were used as the nature of the industries are varied. This is because of the characteristics of data sources which permitted the researchers to follow the multi-methods. This helps the analysis to triangulate the data obtained and increase the reliability of the research outcome and its decision. The companies’ establishment time and its engagement in operation, the number of employees and the proportion it has, the owner types (government and private), type of manufacturing industry/production, types of resource used at work, and the location it is found in the city and around were some of the criteria for the selections.
The determination of the sample size was adopted from Daniel [5] and Cochran [6] formula. The formula used was for unknown population size Eq. (1) and is given as
where n = sample size, Z = statistic for a level of confidence, P = expected prevalence or proportion (in proportion of one; if 50%, P = 0.5), and d = precision (in proportion of one; if 6%, d = 0.06). Z statistic (Z): for the level of confidence of 95%, which is conventional, Z value is 1.96. In this study, investigators present their results with 95% confidence intervals (CI).
The expected sample number was 267 at the marginal error of 6% for 95% confidence interval of manufacturing industries. However, the collected data indicated that only 189 populations were used for the analysis after rejecting some data having more missing values in the responses from the industries. Hence, the actual data collection resulted in 71% response rate. The 267 population were assumed to be satisfactory and representative for the data analysis.
The sample size for the experimental exposure measurements of physical work environment has been considered based on the physical data prepared for questionnaires and respondents. The response of positive were considered for exposure measurement factors to be considered for the physical environment health and disease causing such as noise intensity, light intensity, pressure/stress, vibration, temperature/coldness, or hotness and dust particles on 20 workplace sites. The selection method was using random sampling in line with purposive method. The measurement of the exposure factors was done in collaboration with Addis Ababa city Administration and Oromia Bureau of Labour and Social Affair (AACBOLSA). Some measuring instruments were obtained from the Addis Ababa city and Oromia Bureau of Labour and Social Affair.
Data collection methods were focused on the followings basic techniques. These included secondary and primary data collections focusing on both qualitative and quantitative data as defined in the previous section. The data collection mechanisms are devised and prepared with their proper procedures.
Primary data sources are qualitative and quantitative. The qualitative sources are field observation, interview, and informal discussions, while that of quantitative data sources are survey questionnaires and interview questions. The next sections elaborate how the data were obtained from the primary sources.
Observation is an important aspect of science. Observation is tightly connected to data collection, and there are different sources for this: documentation, archival records, interviews, direct observations, and participant observations. Observational research findings are considered strong in validity because the researcher is able to collect a depth of information about a particular behavior. In this dissertation, the researchers used observation method as one tool for collecting information and data before questionnaire design and after the start of research too. The researcher made more than 20 specific observations of manufacturing industries in the study areas. During the observations, it found a deeper understanding of the working environment and the different sections in the production system and OSH practices.
Interview is a loosely structured qualitative in-depth interview with people who are considered to be particularly knowledgeable about the topic of interest. The semi-structured interview is usually conducted in a face-to-face setting which permits the researcher to seek new insights, ask questions, and assess phenomena in different perspectives. It let the researcher to know the in-depth of the present working environment influential factors and consequences. It has provided opportunities for refining data collection efforts and examining specialized systems or processes. It was used when the researcher faces written records or published document limitation or wanted to triangulate the data obtained from other primary and secondary data sources.
This dissertation is also conducted with a qualitative approach and conducting interviews. The advantage of using interviews as a method is that it allows respondents to raise issues that the interviewer may not have expected. All interviews with employees, management, and technicians were conducted by the corresponding researcher, on a face-to-face basis at workplace. All interviews were recorded and transcribed.
The main tool for gaining primary information in practical research is questionnaires, due to the fact that the researcher can decide on the sample and the types of questions to be asked [2].
In this dissertation, each respondent is requested to reply to an identical list of questions mixed so that biasness was prevented. Initially the questionnaire design was coded and mixed up from specific topic based on uniform structures. Consequently, the questionnaire produced valuable data which was required to achieve the dissertation objectives.
The questionnaires developed were based on a five-item Likert scale. Responses were given to each statement using a five-point Likert-type scale, for which 1 = “strongly disagree” to 5 = “strongly agree.” The responses were summed up to produce a score for the measures.
The data was also obtained from the expert’s opinion related to the comparison of the knowledge, management, collaboration, and technology utilization including their sub-factors. The data obtained in this way was used for prioritization and decision-making of OSH, improving factor priority. The prioritization of the factors was using Saaty scales (1–9) and then converting to Fuzzy set values obtained from previous researches using triangular fuzzy set [7].
The researcher has measured the workplace environment for dust, vibration, heat, pressure, light, and noise to know how much is the level of each variable. The primary data sources planned and an actual coverage has been compared as shown in Table 1.
Planned versus actual coverage of the survey.
The response rate for the proposed data source was good, and the pilot test also proved the reliability of questionnaires. Interview/discussion resulted in 87% of responses among the respondents; the survey questionnaire response rate obtained was 71%, and the field observation response rate was 90% for the whole data analysis process. Hence, the data organization quality level has not been compromised.
This response rate is considered to be representative of studies of organizations. As the study agrees on the response rate to be 30%, it is considered acceptable [8]. Saunders et al. [2] argued that the questionnaire with a scale response of 20% response rate is acceptable. Low response rate should not discourage the researchers, because a great deal of published research work also achieves low response rate. Hence, the response rate of this study is acceptable and very good for the purpose of meeting the study objectives.
The pretest for questionnaires, interviews, and tools were conducted to validate that the tool content is valid or not in the sense of the respondents’ understanding. Hence, content validity (in which the questions are answered to the target without excluding important points), internal validity (in which the questions raised answer the outcomes of researchers’ target), and external validity (in which the result can generalize to all the population from the survey sample population) were reflected. It has been proved with this pilot test prior to the start of the basic data collections. Following feedback process, a few minor changes were made to the originally designed data collect tools. The pilot test made for the questionnaire test was on 10 sample sizes selected randomly from the target sectors and experts.
The secondary data refers to data that was collected by someone other than the user. This data source gives insights of the research area of the current state-of-the-art method. It also makes some sort of research gap that needs to be filled by the researcher. This secondary data sources could be internal and external data sources of information that may cover a wide range of areas.
Literature/desk review and industry documents and reports: To achieve the dissertation’s objectives, the researcher has conducted excessive document review and reports of the companies in both online and offline modes. From a methodological point of view, literature reviews can be comprehended as content analysis, where quantitative and qualitative aspects are mixed to assess structural (descriptive) as well as content criteria.
A literature search was conducted using the database sources like MEDLINE; Emerald; Taylor and Francis publications; EMBASE (medical literature); PsycINFO (psychological literature); Sociological Abstracts (sociological literature); accident prevention journals; US Statistics of Labor, European Safety and Health database; ABI Inform; Business Source Premier (business/management literature); EconLit (economic literature); Social Service Abstracts (social work and social service literature); and other related materials. The search strategy was focused on articles or reports that measure one or more of the dimensions within the research OSH model framework. This search strategy was based on a framework and measurement filter strategy developed by the Consensus-Based Standards for the Selection of Health Measurement Instruments (COSMIN) group. Based on screening, unrelated articles to the research model and objectives were excluded. Prior to screening, researcher (principal investigator) reviewed a sample of more than 2000 articles, websites, reports, and guidelines to determine whether they should be included for further review or reject. Discrepancies were thoroughly identified and resolved before the review of the main group of more than 300 articles commenced. After excluding the articles based on the title, keywords, and abstract, the remaining articles were reviewed in detail, and the information was extracted on the instrument that was used to assess the dimension of research interest. A complete list of items was then collated within each research targets or objectives and reviewed to identify any missing elements.
Data analysis method follows the procedures listed under the following sections. The data analysis part answered the basic questions raised in the problem statement. The detailed analysis of the developed and developing countries’ experiences on OSH regarding manufacturing industries was analyzed, discussed, compared and contrasted, and synthesized.
Quantitative data were obtained from primary and secondary data discussed above in this chapter. This data analysis was based on their data type using Excel, SPSS 20.0, Office Word format, and other tools. This data analysis focuses on numerical/quantitative data analysis.
Before analysis, data coding of responses and analysis were made. In order to analyze the data obtained easily, the data were coded to SPSS 20.0 software as the data obtained from questionnaires. This task involved identifying, classifying, and assigning a numeric or character symbol to data, which was done in only one way pre-coded [9, 10]. In this study, all of the responses were pre-coded. They were taken from the list of responses, a number of corresponding to a particular selection was given. This process was applied to every earlier question that needed this treatment. Upon completion, the data were then entered to a statistical analysis software package, SPSS version 20.0 on Windows 10 for the next steps.
Under the data analysis, exploration of data has been made with descriptive statistics and graphical analysis. The analysis included exploring the relationship between variables and comparing groups how they affect each other. This has been done using cross tabulation/chi square, correlation, and factor analysis and using nonparametric statistic.
Qualitative data analysis used for triangulation of the quantitative data analysis. The interview, observation, and report records were used to support the findings. The analysis has been incorporated with the quantitative discussion results in the data analysis parts.
The data were entered using SPSS 20.0 on Windows 10 and analyzed. The analysis supported with SPSS software much contributed to the finding. It had contributed to the data validation and correctness of the SPSS results. The software analyzed and compared the results of different variables used in the research questionnaires. Excel is also used to draw the pictures and calculate some analytical solutions.
The reliability of measurements specifies the amount to which it is without bias (error free) and hence ensures consistent measurement across time and across the various items in the instrument [8]. In reliability analysis, it has been checked for the stability and consistency of the data. In the case of reliability analysis, the researcher checked the accuracy and precision of the procedure of measurement. Reliability has numerous definitions and approaches, but in several environments, the concept comes to be consistent [8]. The measurement fulfills the requirements of reliability when it produces consistent results during data analysis procedure. The reliability is determined through Cranach’s alpha as shown in Table 2.
Internal consistency and reliability test of questionnaires items.
K stands for knowledge; M, management; T, technology; C, collaboration; P, policy, standards, and regulation; H, hazards and accident conditions; PPE, personal protective equipment.
Cronbach’s alpha is a measure of internal consistency, i.e., how closely related a set of items are as a group [11]. It is considered to be a measure of scale reliability. The reliability of internal consistency most of the time is measured based on the Cronbach’s alpha value. Reliability coefficient of 0.70 and above is considered “acceptable” in most research situations [12]. In this study, reliability analysis for internal consistency of Likert-scale measurement after deleting 13 items was found similar; the reliability coefficients were found for 76 items were 0.964 and for the individual groupings made shown in Table 2. It was also found internally consistent using the Cronbach’s alpha test. Table 2 shows the internal consistency of the seven major instruments in which their reliability falls in the acceptable range for this research.
Face validity used as defined by Babbie [13] is an indicator that makes it seem a reasonable measure of some variables, and it is the subjective judgment that the instrument measures what it intends to measure in terms of relevance [14]. Thus, the researcher ensured, in this study, when developing the instruments that uncertainties were eliminated by using appropriate words and concepts in order to enhance clarity and general suitability [14]. Furthermore, the researcher submitted the instruments to the research supervisor and the joint supervisor who are both occupational health experts, to ensure validity of the measuring instruments and determine whether the instruments could be considered valid on face value.
In this study, the researcher was guided by reviewed literature related to compliance with the occupational health and safety conditions and data collection methods before he could develop the measuring instruments. In addition, the pretest study that was conducted prior to the main study assisted the researcher to avoid uncertainties of the contents in the data collection measuring instruments. A thorough inspection of the measuring instruments by the statistician and the researcher’s supervisor and joint experts, to ensure that all concepts pertaining to the study were included, ensured that the instruments were enriched.
Insight has been given to the data collectors on how to approach companies, and many of the questionnaires were distributed through MSc students at Addis Ababa Institute of Technology (AAiT) and manufacturing industries’ experience experts. This made the data quality reliable as it has been continually discussed with them. Pretesting for questionnaire was done on 10 workers to assure the quality of the data and for improvement of data collection tools. Supervision during data collection was done to understand how the data collectors are handling the questionnaire, and each filled questionnaires was checked for its completeness, accuracy, clarity, and consistency on a daily basis either face-to-face or by phone/email. The data expected in poor quality were rejected out of the acting during the screening time. Among planned 267 questionnaires, 189 were responded back. Finally, it was analyzed by the principal investigator.
The data were collected from the company representative with the knowledge of OSH. Articles written in English and Amharic were included in this study. Database information obtained in relation to articles and those who have OSH area such as interventions method, method of accident identification, impact of occupational accidents, types of occupational injuries/disease, and impact of occupational accidents, and disease on productivity and costs of company and have used at least one form of feedback mechanism. No specific time period was chosen in order to access all available published papers. The questionnaire statements which are similar in the questionnaire have been rejected from the data analysis.
Ethical clearance was obtained from the School of Mechanical and Industrial Engineering, Institute of Technology, Addis Ababa University. Official letters were written from the School of Mechanical and Industrial Engineering to the respective manufacturing industries. The purpose of the study was explained to the study subjects. The study subjects were told that the information they provided was kept confidential and that their identities would not be revealed in association with the information they provided. Informed consent was secured from each participant. For bad working environment assessment findings, feedback will be given to all manufacturing industries involved in the study. There is a plan to give a copy of the result to the respective study manufacturing industries’ and ministries’ offices. The respondents’ privacy and their responses were not individually analyzed and included in the report.
The result of this study will be presented to the Addis Ababa University, AAiT, School of Mechanical and Industrial Engineering. It will also be communicated to the Ethiopian manufacturing industries, Ministry of Labor and Social Affair, Ministry of Industry, and Ministry of Health from where the data was collected. The result will also be availed by publication and online presentation in Google Scholars. To this end, about five articles were published and disseminated to the whole world.
The research methodology and design indicated overall process of the flow of the research for the given study. The data sources and data collection methods were used. The overall research strategies and framework are indicated in this research process from problem formulation to problem validation including all the parameters. It has laid some foundation and how research methodology is devised and framed for researchers. This means, it helps researchers to consider it as one of the samples and models for the research data collection and process from the beginning of the problem statement to the research finding. Especially, this research flow helps new researchers to the research environment and methodology in particular.
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\\n"}]'},components:[{type:"htmlEditorComponent",content:'Copyright is the term used to describe the rights related to the publication and distribution of original Works. Most importantly from a publisher's perspective, copyright governs how Authors, publishers and the general public can use, publish, and distribute publications.
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Creative Commons Attribution 3.0 Unported (CC BY 3.0) | \n\t\t\t\n\t\t\t 5 October 2011 (2011-10-05) \n\t\t\t | \n\t\t\tCurrently | \n\t\t
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\n\nAll rights to Books and all other compilations published on the IntechOpen platform and in print are reserved by IntechOpen.
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