The United States (U.S.) Clean Water Act triggered over $1 trillion in investments in water pollution abatement. However, treated sewage discharge and untreated runoff water that are contaminated by fecal matter are discharged into California beach waters daily. Warnings are posted to thwart the public from contacting polluted coastal water, according to the California Code of Regulations (CCR). This paper evaluated the current policy by empirically examining the productivity loss, in the form of sick leave, which is caused by fecal-contaminated water along the California coast under the CCR. The findings of this study showed that Californians suffer productivity losses in the amount of 3.56 million sick leave days per year due to recreational beach water pollution. This paper also empirically examined the pollution-to-sickness graph that Cabelli’s classic study theoretically proposed. The results of the research assure that the existing water quality thresholds are still reasonably safe and appropriate, despite the thresholds being based on studies from the 1950s. The weakness of the CCR lies in its poor enforcement or compliance. Better compliance, in terms of posting pollution advisories and increasing public awareness regarding beach pollution effects on health, would lead to a significant decrease in sick leaves and a corresponding increase in productivity. Therefore, this study advocates for stronger enforcement by displaying pollution advisories and better public awareness of beach pollution effects on health. California beaches attract 23 million residents and 150 million tourists each year . As a reEpidemiological studies have suggested that exposure to recreational waters that are polluted by animal and human waste may result in illnesses, which include respiratory diseases, gastrointestinal illnesses (GI), and skin, eye, and ear infections ,11,12,13In addition, several papers examined the health effects of visiting polluted California beaches ,18,19. FSwimming beaches are required to be monitored for fecal bacteria to protect the swimmers from contacting feces contaminated water, according to the California State Legislation Assembly Bill 411 (AB 411) . The CalIn contrast to the previous literature, this study aims to empirically examine the fecal pollution-to-sickness relationship in coastal California under the current regulations. Sickness is considered to be a type of negative health shock and it may cause productivity loss among workers. This productivity loss is measured by the number of leaves reported by participants of the Current Population Survey (CPS). This study exploited arguably exogenous variations in coastal water quality and the policy thresholds, and estimated the increase in the sick leaves among the local working population that resulted from beach water fecal contamination under the current policy. In addition, this study provided the first empirical version of the theoretical pollution-to-sickness curve in Cabelli’s benchmark study . This inThe ENT data that were used in this study were obtained from the California Environmental Data Exchange Network (CEDEN). The State Water Resources Control Board manages the CEDEN to record the surface water quality test results ,27. ThisThe 2004–2013 waves of CPS were used to measure the amount of sick leave. This study observed individuals between 18 and 65 years of age who have a valid report of their race, ethnicity, gender, employment status, and sick leave. Sick leave is a YES or NO to the question, in which participants were asked “Have you ever taken a sick day from a labor market activity during the week before the CPS interview?”, where a labor market activity is a combination of working full-time, working part-time, and job search. This study linked the pollution indicators that were derived from the CEDEN to individuals in the CPS using the month, the year, and the longitude and latitude of the sampling locations. The data were kept for people who live in the California CBSAs that have a beach within their borders with at least one sampling location that consistently gathered ENT density data. These individuals live in the following cities: Los Angeles, Long Beach, Santa Ana, Salinas, San Diego, Carlsbad, San Marcos, San Francisco, Oakland, Fremont, San Luis Obispo, Paso Robles, Santa Barbara, Santa Maria, Goleta, Santa Cruz, Watsonville, Santa Rosa, Petaluma, Oxnard, Thousand Oaks, and Ventura. This process left us with 501,110 individuals. This section introduced the empirical strategies, where the study took advantage of the arguably exogenous variation in the degree of pollution of the coastal residents’ local beach waters. The empirical model in this study is more sophisticated than the models that were adopted in related studies. As stated in the introduction, several papers examined the health effects of visiting polluted California beaches ,18,19. HConcerns for endogeneity after controlling for the independent variables in this model are low for the following reasons. First, the identification strategy that is used in this model not only relies on the fecal matter density, but also on the pollution criteria that are set by the government. Individual behavior must be somehow guided by the degree of pollution on local beachline for an omitted variable bias to occur. This is very unlikely, as individuals cannot predict the water quality with sufficient accuracy for a number of reasons. Fecal pollution in coastal waters is barely noticeable or observable with the naked eye. This type of pollution varies drastically day to day and responds primarily to the upstream pollution conditions tens of miles away from the coast. Fecal pollution is also largely influenced by events that are unrelated to health, such as an upstream city’s garden irrigation schedule or a sewage treatment plant’s release schedule. Official reports of water quality are usually days, if not weeks, behind the calendar day. Hence, individuals cannot predict the water quality with a sufficient degree of accuracy.® software.Equation (1) shows the reduced-form relationship between pollution and the number of forgone work or job-search days. Below is the empirical model that was adopted. Equation (1) was estimated while using the STATASick Leave, which a dummy indicator of taking sick leave in the previous week for an individual (i) in CBSA (g) and survey month (t). Polluted is the fraction of beachline that violated CCR policy in the residents’ CBSA in the month of the survey. The primary definition of Polluted is determined by the monthly GM threshold of 35 cfu/100 mL that the California regulations recommend. First, the geometric mean of each month’s ENT levels was calculated using the daily ENT according to the policy recommendations. Subsequently, this monthly GM was evaluated against the California regulations’ monthly GM criteria of 35 cfu/100 mL to determine whether the sampling location was contaminated for that month. The average probability of contamination across sampling locations was calculated to represent the degree of pollution in local coastal water if multiple sampling locations were in the same CBSA. The monthly average probability of violating the STV of 104 cfu/100 mL is treated as a secondary measure and used in the robustness tests. Productivity loss is measured with ε is the random error. The 2004–2011 monthly rainfall (measured in mm) was retrieved from the CDC Wonder, which was used in the robustness checks. The covariates in X include the demographic variables for individual i, which include race , ethnicity (Hispanic and non-Hispanic), and gender fixed effects. X also includes the employment status, which is a determinant of health . γ is a This study considers agram of , the patThe results in panel A were replicated using an alternative STV measure in panel B of Panel A of This section explores the effectiveness of the criteria from two aspects: whether people comply with warning signs and whether the monthly/daily thresholds are sufficiently low to be at safe levels. Surprisingly, comparing the two figures shows that the pollution thresholds were set at a close-to-ideal level, and these thresholds should be reasonably safe. The theoretical prediction of the pollution-illness curve matches well with the shape of the empirical curve shown in The lack of compliance with the policy is also what is surprising. Perfect compliance to the policy would imply that, whenever pollution exceeds the monthly GM threshold, a warning sign is posted, and everyone would follow the sign. The coefficient to the right of the threshold should be zero, because no one would have been exposed to polluted water. One would expect To further test whether compliance is improved with the high STV threshold, a similar exercise was performed using the various levels of STV in This study estimated the 3.56 million sick leave days per year due to polluted recreational water exposure among all Californians. This number is generally consistent with the GI infection predictions for Orange County’s Newport and Huntington Beaches based on historical pollution-to-sickness estimates . The twoBased on this study, the importance of the AB 411 to public health should not be underestimated, but it is important to note that these GM and STV criteria came into being rather haphazardly, for the purpose of fully understanding this policy. These criteria were converted from the coliform thresholds that were released by National Technical Advisory Committee in 1968 . These cThe effectiveness of the water quality criteria was assessed by two tests in this study. The first test is to determine the safeness of the monthly/daily water quality thresholds. These tests are important for a number of reasons. First, the only enforcement method is posting warning signs or closure signs. It would be beneficial for policymakers to test whether this is sufficient for preventing exposure to contaminated coastal water. Second, the California regulations have set the monthly GM pollution threshold for warning the public at 35 cfu/100 mL of ENT. This ENT standard is an arbitrary conversion of a debatable threshold measured using the fecal coliform density. Therefore, it is useful to see whether an empirical test that is based on ENT renders the ideal disease-prevention effect as is theoretically deduced. Surprisingly, the results indicate that the somewhat outdated pollution thresholds are reasonably safe and appropriate. The empirical pollution-to-sickness curve matches well with the theory that was proposed by Cabelli . The theThe second test focused on whether the recreators comply with the warning signs. As previous discussions suggested, our study should expect a significant decrease in the size of the effect when the thresholds were exceeded if compliance to the policy is high. The lack of enforcement of the policy is an alternative explanation for the lack of compliance. Brinks et al.  mentioneThis study assesses the existing California Code of Regulations that controls the beach water quality monitoring for fecal contamination and determines the productivity losses due to exposure to beach fecal contamination. The hypothesis is that successful regulation would lead to no productivity losses. The study found a 0.6 percentage point increase in sick leave when the GM criterium is exceeded, which translates into 3.56 million sick leave days per year in coastal California. Furthermore, the regression model that was used is robust to alternative specifications. The results reveal that the beach water quality criteria are set at reasonably safe levels. However, the enforcement of the regulations needs to be strengthened to prevent visitors from going to polluted beaches. Public awareness of beach pollution effects on health should also be increased to prevent illness.


Significant research on the epidemiology and natural history ofchildhood cancer took place in the Universities of Oxford and Birmingham oversixty years. This is the first of three papers recording this work and describesthe Oxford Survey of Childhood Cancers (OSCC), the largest case-control survey ofchildhood cancer ever undertaken.The OSCC studied deaths in Britain from 1953 to 1981. Parents wereinterviewed and medical records from ante-natal clinics and treatment centres werefollowed up and abstracted. The survey left Oxford in 1975 and was runsubsequently from Birmingham. The data are now being documented and archived tomake them available for future study.Many papers have resulted from this survey, most notably thoserelating to the association first reported therein between childhood cancer andante-natal X-raying. This paper is a historical review of the OSCC.In spite of many analyses of the study, this historic data set hascontinuing value because of the large number of examples of some very rare tumoursand the detailed clinical and family history data that are available; and alsobecause of the possibility of carrying out new analyses to investigate emergingresearch issues. The intention of thesepapers is to summarise the history and achievements and to record the currentavailability of the very substantial research resources accumulated over thisperiod. This first paper describes the genesis and achievements of the first part ofthe work, the Oxford Survey of Childhood Cancers (OSCC). The second of thesepapers3The OSCC was started by a remarkable woman, Dr Alice Stewart. She wasborn in Sheffield in 1906, the daughter of two progressive liberal doctors, fromwhom she inherited a life-long passion for social justice and an almost iconoclasticattitude to established beliefs. She studied medicine at Cambridge, an uncomfortableplace for a female medical student in 1920s, and completed her training at the RoyalFree Hospital, where she established herself as a brilliant young diagnostician. Shecame to Oxford in 1941, initially working under Dr Leslie Witts, but was soonappointed to the new Institute of Social Medicine. This was set up under ProfessorJohn Ryle, who had given up a prestigious chair in Cambridge to work in the newdiscipline—a large part of which was concerned with what we would now callepidemiology. When Ryle died in 1950, Stewart had started to work on his ChildHealth Study and in particular had decided to investigate the causes of childhoodleukaemia; at that time this disease was perceived to be increasing in incidence;this could well have been partly because antibiotics were curing infectious diseasessuch as pneumonia that would previously have masked an underlyingtumour.Realising that the disease was so rare that following a cohort ofchildren would require a prohibitively large study to detect associations, Stewartembarked instead on a case-control study, itself so ambitious as to deter mostscientists, for which she obtained the death certificates of all children dying ofthe disease in England or Wales. Each was matched with a healthy control childand—after an interval of two (later three) years—the respective mothers wereinterviewed by medical staff recruited from local authorities.4 analysed over 1400 case–controlpairs for children dying in the years 1953 to 1955. The principal finding was anassociation between cancer or leukaemia and irradiation of the foetus in anante-natal X-ray.By any standards, the survey involved an impressive degree oforganisation and would be extremely difficult to repeat in modern times owing todata protection and other legal considerations. Initially, only children dying ofmalignant disease before age 10 were included, though this was later extended toages up to 16 and to include Scotland. Each control child was the first available ona ‘control selection list’ of children matched by sex and date of birth that wascompiled from the birth register for the area in which the index child—or ‘case’—haddied. This enabled the same interviewer to see the parents of both children for themajority of case–control pairs. The first interviews were for children dying in 1953and their controls. The first major publication5 this should be read in conjunction with ascientific appraisal by Wakeford.6This paper describes the development of the survey as it moved fromOxford to Birmingham, its relationship to the CCRG, the scope and limitations of thedata collected and some notable publications describing its principal findings. Adiscussion considers its significance for our understanding of childhood cancer andits scope for further insights. A biography of Alice Stewart was published shortlybefore she died in 2002;7 for Scotland see Boyle,Robertson.8 From that point onwards the Oxford survey teamstarted to collect registration information for children who had survived a cancerother than leukaemia for at least three years, forming the so-called ‘LiveSeries’. It was, however, impossible to find satisfactory controls for thesurviving children, and the original study design—based on ascertainment atdeath—was continued.The association with foetal exposure to X-rays was controversialand inevitably ensured continuing work on the survey. In 1962 there was a newdevelopment, in that national cancer registration became fully functionalthroughout Great Britain; for England and Wales seeSwerdlow;9 had failed to confirm the association. Thedisagreement between Doll and Stewart—exacerbated by the latter’s pugnaciousdefence of her findings—meant that, when Stewart reached retirement age in 1974,it was virtually inevitable that she would be unable to continue her work inOxford. She therefore accepted a research fellowship in the Department of SocialMedicine at Birmingham University and the original survey data left Oxford,initially to the Marie Curie Foundation in Limpsfield, who had kindly agreed tohost the data collection. Later the operation moved to the Department of SocialMedicine in Birmingham; her colleagues Margaret Kinnier Wilson and George Knealealso left Oxford to work in Birmingham. Stewart and her colleagues continued topublish analyses of the survey for some while after data collection ceased, withdeaths for the year 1981, though she increasingly turned her attention to otherinvestigations concerned with ionising radiation. The data were later looked afterin the School of Health and Population Sciences at Birmingham University by GeorgeKnox and Tom Sorahan and papers continued to appear for twenty years. Theseincluded further analyses of the ante-natal X-raying data—a subject that remainedcontroversial, though Doll came to accept that the association was probablycausal,10 not least because of doubts about the cohortstudy, which in any case had limited power. A good account of the controversy overthe causal nature of the association is given byWakeford.11In 1969 Professor Richard Doll was appointed to the Regius Chair ofMedicine in Oxford. Unfortunately, he and Stewart had disagreed publicly andvehemently about the association between childhood cancer and foetalX-raying—mostly on the grounds that the survey could not rely on accurate andequal recollection of hospital episodes by case and control mothers. In fact, thegreatest care had been taken to minimise the potential for case-control bias,notably by checking the mothers’ claims against hospital or clinic records.Nevertheless widespread scepticism remained, partly driven no doubt by reluctanceto accept any danger attached to a widespread and valuable diagnostic tool, butalso because a cohort study1 The data were reorganised to form the NationalRegistry of Childhood Tumours (NRCT), with ascertainment by registration and soincluding an increasing proportion of survivors; the earlier dead cases from theOSCC were included in the register, while new ones were notified by the CCRG tothe OSCC. Figure With Stewart’s departure to Birmingham, the staff and computingresources in Oxford were redeployed to form the CCRG, with the support of theDepartment of Health, as described in Draper, Bithell, Bunch, Kendall, Murphy,Stiller.The main dataset is currently being checked and documented with aview to archiving it, after which it is hoped to make it generally available,subject to the restrictions entailed by data protection legislation and ethicalcompliance. It contains records of 23,764 cases and their controls, though only14,938 (63%) of the cases were adequately traced and interviewed. The originalsurvey data were abstracted from interview forms, copied into ledgers—a systemdesigned before the availability of electronic computers—and only transferred toearly computers from the late 1960s. Provision was made in the data record forover 200 variables, though many of the fields were largely empty since they wereconcerned with recording many possibilities that were not necessarily applicable,for example the disease experience of the children’s relatives. Furthermore, notall the fields were abstracted throughout the study period: typically, questionswould be dropped from successive versions of the interview schedule when analysessuggested that they were unimportant, while new questions would be added to pursuenew investigations. Figure Sex and sex of co-twin if a twin, position in the sibship and anysignificant congenital abnormalities. Birth weight is recorded only from 1961.Data for later years were used in two of the papers on parental smokingdiscussed below; no differences in mean birth weights between cases and controlswere observed.12 for the years 1953–73. This coding wassupplemented by a 4-point code using information from medical records andindicating tumour site , tissue type and tumourposition. For leukaemia, an alternative four-point code was used, givinginformation on the leucocyte count, the predominant cell type, the percentage ofcells of the predominant type, and the predominant type ascertained from anymarrow biopsy; of these, just the leucocyte count was preserved throughout thestudy. After 1973 the ICD coding was replaced byMOTNAC,13 a system recording tumour type and site. Allcases have now all been coded also to the groups and subgroups of theInternational Classification of Childhood Cancer, third edition(ICCC3),14 though for deaths before 1962 the mostdetailed level, the “divisions”, are not available. ICCC3 is based on ICD-O andis better suited to the very different pathology of tumours in children; itincludes separate categories for the principal tumours believed to be ofembryonic origin. For the most part, the diagnoses are taken from hospitalrecords, though where these were unavailable or inaccessible the deathcertificate diagnosis was used.Cases were originally coded to a four-point pathology code basedon the International Classification of Diseases, Sixthedition,Information includes details of immunisations, infections andother illnesses prior to the recorded onset of the tumour.The month and year of death are known reliably; for some casesthe month of birth had to be estimated from age information, mainly for untracedcases since date of birth did not appear on death certificates before 1970.Month of onset of the tumour has been recorded throughout, though this isdifficult to define clearly.This was coded from a list of 244 administrative areas prevailingat the start of the study, recorded until 1973, together with a description ofits urban/rural status. Some coding of birth and death addresses was carried outfor geographical studies, but this has not been preserved.Most of the useful information on ante-natal X-raying focuses onthe first of any abdominal X-ray investigations and includes the reason for theinvestigation, the month in the pregnancy, the number of films believed to havebeen exposed and details of the facility where the investigation was carriedout. The mother’s account of the investigation was checked by following up theradiology records from the clinic concerned.This included the mother’s age and pregnancy history, herillnesses in childhood and in adult life, both before and during the relevantpregnancy; it includes drugs taken during pregnancy for deaths in 1964–79. Forthe years 1953–55 and 1971–1981, smoking histories of both parents were alsoavailable.The age of the father and information on his illnesses and thoseof the sibs are available for some years, while congenital abnormalities, deathsand neoplasms in sibs were recorded for all years.15 As this information is clearly not availablefor the controls, a separate coding based on the interview schedules was alsorecorded.This was coded from the father’s occupation as recorded on thedeath certificate using the Registrar General’s Classification ofOccupations.At first sight, the survey has very considerable scope forthrowing light on the possible causes of childhood cancer and leukaemia, butthere are distinct limitations to the data available. For one thing, thepossibility of case-control recall bias means that, for many of the variables,simple case-control comparisons may not be trustworthy, though in the case ofante-natal X-raying considerable care was taken to verify the information. Thereis still the possibility for comparison with external data and for internalcomparisons amongst the cases, looking, for example, for associations specificto particular tumours; the data do however need to be treated with considerablecare. It must be remembered too that the survey was conducted over many yearsand inevitably the main energy of the investigators had to be expended onexploring new findings rather than checking past data and maintainingconsistency of coding over successive years. Many of the interviewers andcoders, though highly motivated and devoted to the aims of the survey, had notbeen trained in data management, with consequential scope for errors in datarecording. It is also the case that the amount of information declined in thesecond half of the period: the number of deaths ascertained per year declinedfrom over 1000 to around 600 between 1968 and 1981, partly because of improvingsurvival.Nevertheless, we feel that there is considerable usefulinformation in the survey, not least because childhood cancer is a disease withmany variants and facets and the possibility of examining small subsets indetail is of continuing value. Some of the diseases in the spectrum are veryrare and the OSCC is by far the largest survey of affected children everconducted. Unfortunately, the possibility of checking the source documents isvery limited: many of the specialist forms, such as those sent to ante-natalclinics, no longer exist, though the interview forms themselves weremicro-filmed and the images have since been digitised. For the cases dying in1961-1981, hospital records still exist on paper and it is planned to scan theseand incorporate them into the archive; this information is of variable qualityand extent, but the records are potentially valuable in following up particularcases of interest.Since the survey began, well over a hundred contributions to thescientific literature have been made that report results from the OSCC; a list ofthe most important and accessible of these can be found online in theSupplementary Information. The largest number of them have related to theassociation with foetal exposure to ionising radiation from ante-natalX-raying.Lancet,16 in which a statistically significantcase-control excess was found amongst the first 547 case-control pairs analysed.This interim result was confirmed by Stewart, Webb,Hewitt,4 who presented a careful and comprehensiveanalysis of the 1416 traced, matched and interviewed cases dying in 1953-55.After certain other exclusions, 1299 pairs were analysed in regard to theirX-ray history. For these, the case-control ratio for abdominal X-raying in therelevant pregnancy was 178/93, resulting in an estimated odds ratio of 2.06 inan unmatched analysis; the paper does not report the data in a form permitting amatched pairs analysis. Even in a careful reanalysis adjusting for possiblesources of bias, the association was statistically significant (P < 0.002).The excess risk appeared to apply to malignant disease in general and alreadythere was evidence of a systematic increase in risk with the number of filmsreported or estimated to have been exposed. Later estimates generally showed adecline in odds ratio over time, for example to 1.47 estimated from an analysisof 8513 pairs;17 these cases include older children dying underage 15 up to 1967 and the paper reported significant increases in risk fortumours other than leukaemia.This association was the most significant finding in the firstanalyses of the survey data and it has remained so in spite of numerousinvestigations of other topics. The association was first reported in aPreliminary Communication in the 18 which shows a decreasing risk per X-ray filmexposed, analysed by birth cohort for deaths to 1972. The widths of theconfidence intervals reflect the changing amounts of information in thedifferent cohorts, the largest numbers of cases being in the middle of the timerange; the decline is evidence supportive of a causal inference drawn from theassociation.This decline in risk is almost certainly due mainly to the lowerdoses delivered by the X-ray equipment in use, as is strongly suggested byFig. 19 now generally regarded as appropriate formatched case-control designs. Knox et al.20 used this methodology in awide-ranging analysis of the study variables, and showed some frequency data,but report an exaggerated relative risk (RR) of 1.94 which resulted from anerror in the analysis, corrected by Muirhead and Kneale21 and discussed by Wakefordand Little.22 Gilman et al.23 also present frequencydata.Some of the early papers reported analyses of X-ray risk usingmethods that were innovative though controversial; latterly, however, Kneale andhis colleagues mainly used conditional logisticregression,24 there was clearly very considerable variationbetween hospitals in dose delivered, even after allowing for substantialdifferences over the dates of the examination and the type of procedure. Acareful analysis is provided by Wakeford, Little,22 who estimate, albeit withvery considerable uncertainty, that intrauterine exposure to X-rays caused anincrease in absolute risk of cancer or leukaemia under 15 years of the order of0.008% mGy-1, while Doll,Wakeford10 assess the evidence in the light ofcontroversial issues raised. Gilman, Stewart, Knox,Kneale25 give an overview of the changes in obstetricpractice over the period of the study and demonstrate the increasing use ofultrasound investigations from 1972, for which Kinnier Wilson,Waterhouse26 found no evidence of an associatedcarcinogenic risk.Attempts to estimate the risk per unit of radiation arefrustrated by a lack of information on the radiation doses delivered by theequipment, which almost certainly varied considerably. Such information as wasavailable at the time is comprehensively reviewed byMole:27 who found similar resultsto the OSCC in a hospital-based survey with a design that avoided recall bias.There was also an issue of compatibility of the OSCC estimates with those ofother studies, notably estimates obtained by extrapolating from higher doses inthe studies of the survivors of the atomic bombing of Japan. Most of the latterinformation relates to post-natal exposure, which may not entail the same riskas for embryonic exposure. Recent studies of children exposed to CT scans havealso provided some evidence of risk to juvenile tissue from low dose radiationin a range comparable with the OSCC findings.28Wakeford29 discusses the compatibility of these leukaemiarisk estimates; it is becoming clear that the OSCC finding of radiation risk atlow doses can no longer be dismissed as an isolated observation resulting from aflawed methodology.The controversy referred to above, which led to delayedacceptance of the causative nature of the association observed, resulted in partfrom criticisms of the case-control design of the survey, though these werelargely allayed by the paper of MacMahon,4 referred to above, analysedjust the 1416 cases dying in England and Wales from 1953-55 under 10 years ofage, the survey age-range being extended subsequently. The paper gave a modelanalysis of the data, with hand calculations that precluded the moresophisticated statistical methodology now available, but nevertheless examinedpossible biases and confounding factors using ingenious comparisons that arestill well worth studying. For example, where a subgroup showed an excess ofcases over controls, the authors checked to see if the individuals involved werealso more likely to show a difference in reporting information unlikely to berelated to cancer; they generally found consistency between cases and controls.In addition to their analysis of ante-natal X-raying, described above, they drewattention to many of the associations that were the subject of subsequent papersinvolving more cases and demonstrated early indications of significantassociations. Thus, for example, they found reports of serious maternal virusinfections in 10 cases but only one control record; the numbers were too small for individual diseasecomparisons to achieve statistical significance. Importantly, they alsohighlighted the absence of a case-control difference in maternal health beforethe relevant pregnancy, which argues against the possibility that childhoodcancer might be largely determined by an inherited tendency to morbidity orlowered immunocompetence. Other analyses in the paper concern the child’s otherillnesses, treatment and any congenital abnormalities; the family history,including the occurrence of neoplasms in close relatives; and post-natal X-rayexposure of the child. There was no case-control excess for post-nataldiagnostic X-rays; the numbers of cases (8) and controls (3) treated withtherapeutic X-ray treatments were too small to draw useful conclusions.The first major publication,Monthly Bulletin of theMinistry of Health and the Public Health Laboratory Service. Thesedealt with various particular topics, including the completeness ofascertainment of birth cohorts,30 the occurrence of congenital abnormalitiesand deaths in sibs,31 the association of childhood leukaemia andDown syndrome,32 and the comparative reliability of case andcontrol reporting.33 These reports make interesting reading, thoughthey cover deaths only to 1960 and have to some extent been superseded by laterpublications. They are unfortunately not currently available in digital form onthe web.A series of progress reports were published in successive yearsfrom 1963 to 1966 in the 34 Bithell etal.35 carried out an analysis of maternal virusinfections in the OSCC for 9074 children dying in 1953–67. Of the associationswith maternal virus infections during pregnancy reported by Stewart, Webb,Hewitt4 and referred to above, only rubella showed acase-control excess, with 17 cases to 7 controls. Significant excesses forchicken pox and influenza were also observed, though the estimated odds ratiofor the latter of 1.52  was appreciably lessthan that observed in the NCDS cohort, whose mothers were exposed to aparticularly virulent ‘Asian’ strain of the virus in the winter of 1957–58. Inan examination of later OSCC data, Blot et al.36 found no association withchicken pox but did report a persistent case-control excess of maternal rubellainfection.Following a report of a considerable excess of mothers in theNational Child Development Study (NCDS) cohort who were exposed to influenza inpregnancy and whose children developed leukaemia,37 but interpreting these is particularlydifficult because of the possibility of recall bias and also the problem ofdistinguishing the effects of the illness and the treatment. Thus Sanders,Draper38 examined the prevalence of pulmonarytuberculosis and epilepsy, both appreciably more frequent in case mothers thanin controls. They demonstrated, however, that the proportions of mothersaffected by illness who were prescribed certain drugs, in particular isoniazidand phenytoin, were similar between cases and controls, suggesting thatassociation could be attributed to the disease rather than the treatment. In amore comprehensive study, Gilman et al.39 presented an analysis ofall recorded drugs and illnesses using logistic regression, which effectivelyadjusted estimates of individual drug or illness effects for overallcase-control reporting differences. They concluded that the effects of drugstaken during pregnancy were secondary to those of certain illnesses, notablyviral infections and other illnesses involving pyrexia. The only drug groupswith consistent residual effects in the analysis were analgesics, antipyreticsand vaccines.The data show appreciable excesses of reported illnesses anddrugs administered among the cases compared with thecontrols,40 revealed no important effect of parentalalcohol consumption or maternal smoking on childhood cancer risk, but a highlysignificant trend with tobacco use by the children’s fathers (P < 0.001), confirming an association found fromother, smaller studies. This trend was also confirmed in analyses of data fromthe OSCC for two further periods, the effect applying across tumour groups,though concentrated mostly on leukaemias and lymphomas. Sorahan etal.41 present the data for 1953–55 and review theliterature, while Sorahan et al.42 analyse data for the years 1971–76 anddiscuss possible mechanisms for what may turn out to be a causal link.A study of 1641 matched pairs for the years1977–814summarised data on eight reports of possible deaths from malignant disease insibs of the survey cases. In five of these they considered that the reports didindeed indicate that the sib died of malignant disease. In a subsequent progressreport Barber and Spiers31 updated these results and reported 31 deathsfrom neoplasms compared with an expected number of 7.9, giving a RR of aboutfour—though a later paper based on larger numbers and a more closely definedmethod of analysis gave different results.43 This latter paper,published at the time the Department of Social Medicine in Oxford was beingtransformed and the CCRG was opening, gave estimates of the risks to sibs ofcases for various diagnostic groups. Excluding twins, cases of retinoblastoma(of which many are associated with RB1 gene germ cell mutations), and familieswith genetic disease having a recognised increased risk of childhood cancer, thecalculated risk that a sib of a child with cancer would also be affected bycancer below age 15 years was double the normal risk. For genetic counselling,the estimates in this paper are to be preferred to earlier ones.In the first major paper from the OSCC referred to above, Stewartet al.44 suggested that this was because a member ofa pair affected in utero may have an increased risk of dying before the twinpregnancy is recognised as such. They argued that this conclusion was supportedby the finding that the twin deficit applied especially to members of like-sexpairs, and that this could reflect prenatal selection against embryos with adisposition to develop cancer in childhood. Twin concordance, the likelihood ofboth members of a twin pair having childhood cancer, is discussed in Draper etal.;1that discussion is based partly on findings from the OSCC.Twins are less likely than singletons to develop childhoodmalignant disease. Hewitt et al.45 on background radiation, Knox andGilman46—one of a series of papers on clustering—andKnox,47 the last in a series of papers onenvironmental pollution. The geographical potential of the OSCC is limited,however, by having relatively imprecise address coding and incomplete caserepresentation, particularly for the later years, when an increasing number ofchildren have survived the disease. These studies may reasonably be regarded asless reliable than subsequent analyses of registration data as described in thecompanion paper.1A number of geographical studies have been published using OSCCdata; see, for example, Knox et al.48 data from the OSCC were combined with datafrom the NRCT and from a separate Scottish study49 and used to assess thecancer risk to the children of exposed workers in radiation related industries.Records from the National Registry for Radiation Workers were used to identifythe parents of cases and controls who were occupationally exposed prior to theconception of the child. The numbers of such parents linked were small and, asreported in Kendall et al.2 the results were not indicative of a risk:although there was an excess of radiation workers amongst the parents of cases,there was no indication of a dose–response effect. A follow-up paper by Sorahanet al.50examined the timing of the workers’ exposure and found significant associationswith exposure at conception and at diagnosis, but concluded that it was notpossible to distinguish these effects.In a collaborative study on the risk to the children of radiationworkers,The archiving project referred to above is still under way, thoughit is hoped to finish it during 2018–19. At this point, it is planned to lodge theavailable information in an electronic archive, possibly the Richard DollCentenary Archive accommodated within the Nuffield Department of Population Healthin Oxford. It is hoped that it would then be generally available, subject to theterms and conditions laid down by the UK data protection authorities. In additionto the computerised dataset and the digitised interview images, it is planned toinclude the hospital records referred to above. We believe that it would bescientifically beneficial if responsibility for the data could be assumed by anepidemiological unit with interests in paediatric oncology, so that licensedaccess to the available information could be maintained.Without in any way wishing to diminish the impact of other surveysof childhood cancers, we believe that the OSCC, as the largest case-control surveyof the diseases ever undertaken, has had a very significant impact on ourunderstanding of their aetiology. The expectation that strong associations withexogenous factors, similar to those observed for many adult cancers, might existhas not been fulfilled and such associations as have been observed have beenmodest. This is true even for pre-natal X-raying—almost certainly the mostimportant association reported by the OSCC.10 In spite of initial resistance to acceptanceof a causal relationship, the finding played a major part in the abandonment ofroutine ante-natal X-rays and their replacement byultra-sound.25 Of possibly greater significance has been theimpact on our understanding of the effects of low dose radiation and thewidespread abandonment of threshold models of radiation carcinogenesis. Althoughpractical considerations lead us to accept that some doses may safely beignored—and indeed are unavoidable—it would now seem that no dose of ionisingradiation entails zero risk. This observation may have little impact on a smallscale of human exposure, but it acquires considerable significance when applied tothe exposure of whole populations to small extra doses, as after a nuclearaccident, for example.This one finding, however, has had a very significant effect on ourbeliefs about the risk of low-dose radiation, particularly following more recentanalyses endorsed by Richard Doll.Other associations ascertained from the OSCC have been lessclear-cut, though there are certainly valuable pointers to the possible effects ofsome exogenous factors, including infectious organisms, certain classes of drugstaken in pregnancy and paternal smoking, as discussed above. The importance ofgenetic factors is clear, too, and estimates of familial risk are of considerablevalue for genetic counselling.Accepting that the associations detected are fewer and weaker thanwould be expected for adult cancers is of value in itself, particularly as it hasbeen possible to exclude a number of life-style and other factors that can worrymothers with affected children or with children as yet unborn. The foetus is wellprotected in pregnancy and it has become increasingly certain that few if any ofthe ordinary impacts of everyday life pose a risk of cancer in the unbornchild.It is clear that the total risk attributable to the associationsidentified remains very modest and the conclusion must be that the ‘cause’ of mostcases is unknown, except to the extent that it would seem to be influenced bygenetic attributes, endogenously determined, that are only slowly beginning to beunderstood. The value of the OSCC is clearly limited by the absence of geneticmaterial; nevertheless the large number of possible associations and thedescriptions of a significant number of cases, some of very rare tumours, suggestan enduring potential for continuing research.OSCC Publications


This article investigated the knowledge and practice of a nature-based solution to reduce disaster risks of drought, veld fires and floods using wetlands in the eastern Free State, South Africa. A mixed research method approach was used to collect primary data using three data collection tools, namely questionnaires, interviews and field observations. Ninety-five wetlands under communal and private ownership as well as a few in protected areas were sampled, with their users completing questionnaires. The study showed that communal wetlands were more degraded, while wetlands in protected areas and in private commercial farms were in a good ecological state. An extensive literature review reveals that healthy wetlands are effective buffers in reducing disaster risks such as drought, veld fires and floods which are recurrent in the study area. Therefore, through better land-use and management practices, backed by education and awareness, wetlands could be good instruments to mitigate recurrent natural hazards in the agriculturally dominated eastern Free State in South Africa. The eastern Free State where this study was conducted is located in the Free State province, which is one of the nine provinces of the Republic of South Africa. The demarcation of the eastern Free State in this study did not follow any specific political or ecological boundary but was arbitrarily designed to closely follow the 28 ºE meridian and a vertical line that passed through the 500 mm – 700 mm isohyets; east of this line, rain-fed agriculture (the dominant activity in the Free State province) is feasible. The demarcated study area also separated the dry grassland in the west from the moist grassland in the east Collins  see Fig. The chomokhoabo in Sesotho, umgxobhozo in isiXhosa, vlei in Afrikaans and wetlands in English, wetlands have different names in South Africa. The South Africa National Water Act Republic of South Africa Water Act , the Free State has the highest number of wetlands in South Africa  and vulnerability (V) compared with the coping or adaptive capacity (C) of the community, structure or system (R = H × V/C) UNISDR . While tTen indicators were designed and used , to distinguish them from communally owned wetlands which were collectively owned without an identifiable manager. In total, 95 wetlands were sampled. Face to face and telephonic interviews were conducted with five wetland specialists, eight environmental and disaster management specialists and two environmental law specialists in the Free State province. Lastly, though field observations were carried out in most of the wetlands during the administration of the questionnaire, detailed observations were carried out on 21 randomly selected wetlands . The communal wetlands were located in Monontsa, Bethlehem, Clarens, Heilbron, Petrus Steyn, Edenville and Frankfort, and the privately owned wetlands in Swineburne and Van Reenen’s Pass in the Harrismith area. The three protected wetlands included Seekoeivlei, Golden Gate and the Eskom wetland systems at Ingula Power Station. Furthermore, a pilot study was conducted in six wetlands: two in protected areas, two on communal land and two on private land. Three Master’s students, three PhD students and three senior researchers tested the questionnaire before the pilot study. These measures added validity and reliability to the data  had used the wetland for more than five years, of which 60% had more than 10 years’ experience . Most prCommunal wetland respondents indicated that flood and veld fires affect them more, while private wetland owners felt that they were more affected by floods than drought as they use their wetlands mostly for commercial agriculture . It shouBesides the above mentioned threats, private wetlands owners also perceived a lack of awareness on wetland benefits to be a major threat to their wetland .The following activities were reported by respondents as poor wetland management practices that led to wetland degradation:Overgrazing. This practice stemmed from overstocking livestock and game as well as the use of the wrong game species. Overgrazing was generally observed during the dry winter season.Poor fire management planning as well as uncontrolled runaway fires.The introduction of both invasive and alien species in and around the wetland.The drainage of wetlands for agricultural practices, human settlement and road construction.The construction of dams for irrigation and electricity production.The pollution of wetlands from heavy agricultural chemicals and poor waste disposal.The uncontrolled harvesting of wetland vegetation, herbs and medicinal plants.Poor grazing practices such as grazing the permanently wet areas of the wetlands, which causes animal trampling.The ecological status of a wetland was used as a proxy to assess its level of vulnerability to imminent hazards and consequently its ability to mitigate those hazards. Respondents were requested to score the current state of their wetlands against the key wetland parameters of vegetation, water and soil . The resThe ecological status derived from the 10 indicators is summarised in The results from field observations tally with the interview results from five wetland specialists. Based on their past experiences, all specialists reported that protected wetlands at Golden Gate, Mamel and Ingula were in a very good condition apart from a few head-cut erosions. They also reported that most wetlands on private commercial farms were in a good state. Those identified as having problems were being rehabilitated by the Working for Wetlands Programme. Communal wetlands were generally in a poor state despite efforts to rehabilitate some of these areas. The main problems that were reported in communal wetlands were open, uncontrolled grazing and other commercial activities like sand excavation within the wetlands. The conversion of the Dihlabeng wetland in Bethlehem into a mall was also cited.The communal respondents responded negatively when asked whether wetlands help them to reduce the common hazards in the area . Their responses are summarised in In private wetlands, 69.9% had no wetland management plans, while 12% had plans that were seldom used and revised. A high percentage of these wetlands (85.5%) had a limited protection status or none at all. Another 75.9% reported that they did not know the threats facing their wetland, and therefore could not address the threats or insufficiently addressed them. Another 85.5% either had no mechanisms in place to control inappropriate land-use activities, or the mechanisms were ineffectively implemented. What was noted from these responses was that there was no comprehensive and holistic knowledge of wetland threats in the area. Besides the threats of drought, floods and veld fires, there are other stressors that affect wetlands in varying degrees in the area – drainage and land-use conversion of wetlands. The conversion of the Dihlabeng wetland in Bethlehem into a mall, climate change, ineffective implementation of policies related to wetlands, ignorance of the functions and values of wetlands and so on were either observed or reported during interviews.The field observations showed that most of the wetlands in the study area were used for grazing. For example, all communal wetlands were used for small-scale grazing. A few wetlands were cultivated – mainly for maize, beans and sunflowers – and only two wetlands were used entirely for conservation. This information is summarised in Respondents from communal wetlands indicated that they were more vulnerable to the risk of floods than veld fires and drought. This can be explained by many factors. First, the communal wetlands that were sampled were channelled, valley-bottom wetlands, which easily collect and channel rainfall in the catchment. Second, unlike flood plain wetlands, valley-bottom wetlands are less efficient in attenuating flood waters and mitigating the risk of floods Kotze . Third, Foremost in the ranking of perceived threats to private wetlands was the lack of awareness of wetland benefits, followed by uncontrolled fire and then overgrazing. The Kendall’s W Test confirmed the perception that there was an urgent need for education and training on wetland management. The test statistic for the ranking of the threats revealed that about 93% of the private wetland owners agreed to a ranking order as provided in From the field observations, six out of seven communal wetlands were in a poor state, with only one in an average ecological state. All the wetlands in protected areas were in an excellent ecological state, with one of them (Seekoevlei) being a Ramsar site. The Ingula wetland (one of the protected wetlands) could eventually qualify for a Ramsar site designation, given its present status and ecological functions. Wetlands found on private commercial farms were clustered around a good ecological status. One of them was in excellent ecological health, and this wetland is also a heritage site. Most protected wetlands were therefore in a very good to excellent ecological status; those on private land were in an average to good ecological status; and those on communal land mostly had a poor ecological status . This stWetlands can be managed to reduce the impact of disaster risks as well as to adapt to climate change. This is popularly referred to as the ecosystem-based disaster risk reduction and climate change adaptation (Eco-DRR/CCA) approach,  from both private and communal wetland users was the need to provide education and training on the importance, conservation, protection and wise use of wetlands . This waThe common ownership with no control over communal wetlands makes the management planning of wetlands almost non-existent in the study area. There were no management plans, written or unwritten, for communal wetlands and there was no observed control of illegal activities such as pollution. For example, at the Monontsha wetland, a channel was constructed to direct waste from a pig sty into the wetland, causing pollution to downstream users. Private commercial farmers reported that they had management plans for their wetlands although these plans were not documented and regularly revised as opposed to those in protected areas.With no adequate education, awareness and training on wetlands management, the absence of management plans in most wetlands (no specific wetland policy to guide wetland management in the study area), points to the fact that the fate of the majority of these wetlands depends on the ingenuity, guess work and experience of the individual users. Better management plans and processes were observed in the three protected and conserved wetlands that were included in this study . The Working for Wetlands Programme has, however, been rehabilitating many wetlands in communal and private commercial farms in the area, but this approach is too reactive and spontaneous.Communal wetlands are in a very poor ecological state as opposed to protected wetlands and those on private commercial farms in the eastern Free State. The risk of veld fire and drought are high in the study area, and this has serious negative impacts on agriculture and grazing, which are the dominant activities in the Free State province. Grazing is the dominant economic activity in the sampled wetlands. Well-managed wetlands can effectively reduce the risk of veld fires, floods and drought, as observed in the field and supported by the literature review. This is the case with wetlands in protected areas and on private commercial farms in the study area. On the contrary, degraded wetlands lack the capacity to mitigate risks, as observed in communal wetlands. Education and awareness on the role of wetlands in reducing recurrent disaster risks in the area is crucial, especially among the communal wetlands users. The current climate variability adds to the need for education on proper wetland management, awareness and the development of holistic wetland management plans that should constantly be revised and carefully implemented to accommodate the changing external environment.Proper training on the use and management of wetlands is also vital. The University of the Free State (UFS) and Central University of Technology (CUT), the leading tertiary institutions in the area, could design courses on wetlands management, while the Working for Wetlands Programme could offer skills enhancement courses to the local communities. The Mondi Wetland Programme (MWP) and the Endangered Wildlife Trust (EWT), which are prominent non-governmental organisations (NGOs) with an important role to play in wetlands management in South Africa, are not prominent in the study areas. They could also assist in capacity building in the area regarding wetlands issues.It is important to rehabilitate the degraded communal wetlands as well as monitor the ecological status of wetlands on protected and private farms. This can be performed by the Working for Wetlands Programme and supported by the Working for Water Programme, which has the assigned responsibility from government of the clearing of invasive species that may include those in wetlands. These programmes should be more capacitated with both financial and human resources so that they can function effectively.Wetlands could be a cost-effective, community-driven, bottom-top approach in mitigating the recurrent risks of drought, veld fires and floods in the eastern Free State if wetlands are properly managed. This ecosystem-based approach to reduce disaster risk and adapt to climate change has received and continues to receive much international attention in recent years.


Ventilator-associated pneumonia (VAP), a hospital acquired pneumonia that occurs more than 48 h after mechanical ventilation, is a common complication of mechanical ventilation with a high mortality rate. VAP can cause patients to have difficulty weaning off the ventilator and to stay in the hospital longer, which results in a huge financial burden to patients and a huge demand for medical resources. Several strategies, such as drugs including chlorhexidine, β-lactam antibiotics and probiotics, have been used to prevent VAP in clinic. The incidence and the mortality rate of VAP have been decreased with the development of preventative strategies in the past decades, but VAP remains one of the most common causes of nosocomial infections and death in the intensive care unit. Current challenges in the management of VAP involved the lack of a gold standard for diagnosis, the absence of effective preventative strategies, and the rise in antibiotic resistance. Therefore, in order to reduce the incidence of VAP and improve the outcome of patients with mechanical ventilation, it is necessary to clarify the risk factors of VAP for clinical prevention and control of VAP. This paper reviews the international risk factors of VAP occurrence reported in recent years, including patient characteristics, increased mechanical ventilation time and prolonged length of hospital stay, disorders of consciousness, burns, comorbidities, prior antibiotic therapy, invasive operations, gene polymorphisms, and mentions the corresponding preventive measures. Each factor is not only an independent risk factor of VAP, but also has an influence on each other. A better understanding of risk factors for VAP is helpful for predicting the occurrence of VAP, improving the prevention and control of VAP, and reducing the morbidity and mortality rates of patients with VAP. Mechanical ventilation is an effective intervention method to save the life of critically ill patients and is widely used in intensive care units (ICUs). Ventilator-associated pneumonia (VAP) is a type of nosocomial infections and occurs after more than 48 h of mechanical ventilation. The 2016 clinical guidelines released by the Infectious Diseases Society of America (IDSA) and the American Thoracic Society (ATS) reported that the mortality rate of VAP in the United States reached up to 13% . While iA retrospective study of 147 patients aged 19–98 years showed that the average age of patients with VAP was 69.9 ± 15.9 years . Some clA prospective cohort study of 747 patients reported that male gender is also an independent risk factor for VAP . Forel eMechanical ventilation is an effective intervention method to save the life of critically ill patients and is widely used in ICUs. However, prolonged mechanical ventilation can lead to increased risk of infection and a variety of complications. VAP is a common complication of mechanical ventilation. In a 2017 retrospective study, it was reported that ventilation time and ICU length of stay were significantly longer in patients with VAP than in those without VAP . MechaniVentilator-associated pneumonia is a common complication in coma patients and may lead to poor prognosis. A study of 100 patients with VAP in Zagazig University showed that the Glasgow coma score in VAP group were significantly lower than that in non-VAP patients. The disorders of consciousness were significantly correlated with the occurrence of early VAP . A studyThe most significant clinical complication after burn is pneumonia, with an incidence of 10–65% . A 5-yeaChronic diseases might be a risk factor for VAP, including coronary disease, diabetes, respiratory diseases, chronic renal failure, and Hashimoto’s thyroiditis . In genePseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, and Acinetobacter, and Gram-positive cocci such as Staphylococcus aureus. Pseudomonas aeruginosa is the most common pathogen of VAP  in the promoter region of tumor necrosis factor α (TNFα) gene on susceptibility to infection are controversial. Some suggest that patients carrying these SNPs alleles are more likely to become infected than those carrying only wild-type alleles . RecentlIn addition to the above risk factors which have been extensively studied, The incidence of VAP in developing countries is much higher than that in developed countries. The reason is that developing countries do not have a good preventive strategy for VAP . It is vThere are various risk factors for VAP occurrence. Each factor is not only an independent risk factor of VAP, but also has an influence on each other. Due to the decline of the physiological and immune functions, elderly patients often have more than one comorbidity, which can lead to an increase in hospital length of stay and mechanical ventilation time, increasing the susceptibility to VAP. The hospital length of stay and the time of mechanical ventilation were significantly prolonged in patients with disorders of consciousness. With the prolongation of hospital stay, invasive procedures in the ICU are also relatively increased, increasing the exposure of patients to the bacterial environment. Therefore, the chance of VAP occurrence has increased greatly. The independence and interaction of these factors have contributed to the occurrence and development of VAP. To identify the risk factors of VAP has a very important guiding role in clinical prevention. In this review, we searched either retrospective or prospective international clinical trials on risk factors for VAP which were published in recent years and performed in a single center or multicenter all over the world. It should be noted that these clinical trials had differences in the sample size of the study, age/sex ratio of enrolled cases, ethnicity and geography, which can lead to inconsistencies in risk factor analysis. In addition, these studies do not have unified diagnostic criteria and treatment measures for VAP, which makes the results lack accuracy. Therefore, further studies with larger sample size and standard definitions for VAP are needed to better understand the global epidemiological characteristics of VAP. Only in this way can we provide more reliable support for better prevention and control of VAP.DW and CW drafted the initial manuscript. All authors developed the concept and design of the study and participated in critical revisions of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The by-products of solid waste deposited in a landfill has adverse effects on the surrounding environment and humans living closer to landfill sites. This study sought to test the hypothesis that the deposition of waste on landfill has an impact on the surrounding environment and residents living closer to it. This was achieved by evaluating the perception of the respondents drawn from people living close (100–500 m) and far (1–2 km) from the landfill site, concerning environmental issues, health problems, and life satisfaction. Results from the study showed that 78% of participants living closer to the landfill site indicated serious contamination of air quality evident from bad odours linked to the landfill site. Illnesses such as flu, eye irritation and weakness of the body were frequently reported by participants living closer to the landfill than those living far from the landfill. More than half of the participants (56%) living closer to the landfill indicated fear of their health in the future. Thus, the participants living closer to the landfill site were less satisfied with the location of their community with respect to the landfill, than those living far from the landfill site. Therefore, the need for a landfill gas (LFG) utilisation system, proper daily covering of waste and odour diluting agents are necessary to reduce the problems of the residents living closer to the landfill site. Landfilandfills ,4,5,6,7.andfills . Some otandfills ,10,11. Tandfills ,10,11,124 by humans can cause loss of coordination, nausea, vomiting and high concentration can cause death [2 by humans increases the susceptibility to respiratory infections [The continuous inhalation of CHse death ,14,15. Ase death . Studiesse death ,17,18,19fections  identififections ,22. Addifections ,22,23.Landfills generate different kinds of trace toxic elements which include carbon monoxide, hydrogen sulphide, xylene, dioxin, etc. Toxic organic micro pollutants also include polychlorinated dibenzo-para-dioxins and polychlorinated dibenzofurans (PCDDs and PCDFs) which are all called dioxins and polycyclic aromatic hydrocarbons (PAHs). Dioxin can be formed from the presence of chlorine-containing substances in the landfill and from landfill fire which is harmful to human health ,17,24,252S) is a colourless and highly flammable gas. It has an odour of rotten egg and contributes immensely to the odour emissions experienced from landfill sites. It is formed when high sulphate containing compounds (like gypsum and plasterboard) are mixed with the degradable waste in the landfill site. When humans are exposed to high levels of H2S it could lead to malfunction of the central nervous system and respiratory paralysis [Hydrogen sulphide -glucans and mycotoxins) ,28. ExpoPrevious research shows that people living closer to landfill sites suffer from medical conditions such as asthma, cuts, diarrhoea, stomach pain, reoccurring flu, cholera, malaria, cough, skin irritation, cholera, diarrhoea and tuberculosis more than the people living far away from landfill sites ,34,35,36Despite the proliferation of the harmful effects in recent years, not much research on health and environmental impacts on the residents living closer to landfill sites has been conducted in many landfills situated in rural and peri-urban centres in South Africa. Though, Bridges et al.  conducteThohoyandou landfill is situated very close to the residential areas at approximately 100 m away. Therefore, this study sought to find out the perceptions of health impact and the way of life for residents living closer to Thohoyandou landfill. Firstly, a reconnaissance survey was conducted around the landfill site to identify the number of households and other functional institutions located in the area. It was observed that the community was located approximately 100 m away from the landfill. Therefore, the study focused on residents living approximately 100 m to 2 km away from the landfill. The households living closer to the landfill were identified to be approximately 100 households, with an average of four people per household . Then, tAccording to Brewer , stratifA landfill operator manager and three university students from the University of Venda, South Africa were trained and recruited for data collection. A five-page questionnaire was pretested with 10 participants to identify errors and limitations of the survey tool. Furthermore, after adjustments of the questionnaire, the questionnaires were administered to a total of 100 participants . At the start of the administration of questionnaires, the majority of the residents were willing to corporate and participate in the study. Additional information, suggestions and recommendations were also given to the researchers by the participants based on the environmental challenges faced by the community. During the fieldwork, four households expressed scepticism and refused to participate in the study. Two other households expressed less concern because they felt the study was not beneficial to them as they were not house owners and not fully responsible for the environmental issues in the community.t-test analysis was conducted to identify the difference in mean, and the significance of results obtained from both communities  serious, (2) a fairly serious problem and (3) not a serious problem. The participants were provided with seven environmental issues facing the community which included disposal of solid waste, garbage, and litter in the street, unwelcome location of the landfill, air pollution, bad odour, water pollution, noise pollution and dust. An independent sample munities .In addition, the participants were presented with possible illnesses associated with complaints of people living closer to the landfill site. The participants were asked to indicate whether they or any member of their family experienced each of the identified illnesses frequently (1), fairly frequently (2) or not frequently (3). The data acquired from the field study were analysed with the aid of Statistical Package for the Social Sciences version 25 developed by International Business Machines Corporation, Armonk City, NY, USA. The social and demographic characteristics of the respondents were identified to understand the social and economic characteristics between the two communities. This indicates the rate of disposition of solid waste in the landfill and considering how serious disposal of Municipal Solid Waste (MSW) activities influence the state and wellness of the people. A total of 30% of the participants living closer to the landfill indicated that garbage and litter in the surrounding CL community was a serious problem , while 2This indicates the suitability and acceptance of the landfill site by the participants from the community. Air pollution and bad odour have been found by many scholars to be synonymous to landfill operations. This shows the seriousness of air pollution and bad odour emanating from the landfill into the community. Sakawi et al.  showed iIn the context of this study, water pollution indicates the presence of polluted water in the community. In addition, noise pollution indicates the level of noise in the community. Furthermore, 58% of participants living closer to the landfill indicated that there is no form of noise pollution, while 22% of participants living far from the landfill indicated the same. However, most of the participants living far from the landfill (52%) indicated noise pollution as a fairly serious problem for them. Noise can be generated from different sources and not necessarily from the landfill. Although, it is quite impossible not to notice the heavy trucks and bulldozers in a landfill, the Thohoyandou landfill lacks the adequate number of bulldozers and heavy trucks in the landfill due to lack of funds. On the day of our visit to the landfill, there were complaints about the bulldozers for daily covering of waste not functioning for several months. However, after some months when we went back to the landfill, some bulldozers were functioning. In addition, incoming waste trucks contribute some noise pollution in the landfill but not enough to cause significant pollution to the nearby residents.The results show that more undesirable environmental conditions posed very serious problems for the participants in the CL community than the AL community. Specifically, disposal of solid waste; unwelcome location of landfill; and air pollution with bad odour; were considered major threats.t-test was employed to access whether the differences noted between the ratings on the significance of the environmental problem by the two locations were statistically significant (p < 0.05). A 10 and PM2.5) and various volatile organic compounds that have been implicated in respiratory diseases [Respondents living close to the landfill reported that breathing disorders are frequently (24%) and fairly frequently 34%) problems they experience in the CL community. Similarly, respondents from the AL community reported that breathing disorders are frequently (10%) and fairly frequently (24%) experienced. Various studies have also shown that residents living closer to a landfill site are more prone to respiratory diseases as supported by this study ,33,34,35% problemdiseases ,50,51,52A study on exposed traffic policemen to outdoor air pollution showed that the percentage of participants with a diagnosis of allergy was higher in the exposed traffic policemen than in the control . AdditioFurthermore, illnesses like flu, eye irritation and weakness of the body were frequently reported by participants living closer to the landfill than participants living far from the landfill . Most paSome illnesses recorded in this study like back pain, skin disorders, hearing impairments and asthma were indicated by most participants living closer to the landfill as not often experienced. Likewise, most participants living far from the landfill did not experience these illnesses often, except for asthma. Studies have established that cancer is an illness experienced by people living closer to a landfill or waste dump ,33. Simit-test analysis was conducted for the most reported illnesses to understand the significance of the difference of results obtained and the result’s significance  disturbing, (2) fairly disturbing or (3) not disturbing to the participants living in both communities as shown in Fear of future health indicates the anticipated health issues that will arise in the future based on the current effects. The viability of properties in the area was also assessed. Results in Additionally, other external factors on landfill characteristics like friend’s unwillingness to visit, desirable business enterprise staying away and landfill stigmatisation, show that most participants living closer to the landfill site felt that these external factors were disturbing to them. Participants living far from the landfill felt their external factors were not disturbing to them except for landfill stigmatisation. However, these communities are still developing and might still lack some desirable businesses and poor rent for properties. Rodents and mosquitoes were indicated to be more prevalent with participants living closer to the landfill than participants living far from the landfill. Therefore, some participants close the doors and windows of their houses regularly to avoid mosquitoes and rodents. t-test was used to test whether the differences noted between the ratings of the disturbances of the external landfill characteristics were statistically significant (p < 0.05) (A  < 0.05) . The CL t-test analysis which was performed to understand the significant differences between both communities  satisfied, (2) somewhat satisfied or (3) not satisfied as shown in munities .The results show that the participants living closer to the landfill site are less satisfied with the variables posed in this study than the participants living far from the landfill site. methanobrevibacter smithii in their intestinal microbiota which caused serious health challenges and unrest in the community [The results show that the differences between the two communities were found to be statistically significant for five out of seven variables, that is for life in general; personal health condition; neighbourhood compared to others; community as a place to live in and perceived neighbourhood change. Palmiotto et al.  showed tommunity . The stuommunity .The study on health and environmental impacts of landfill sites on humans has generated mixed reactions among scholars, therefore, constitutes a complex study. This study evaluated the health and environmental effects of Thohoyandou landfill on the residents living closer to the landfill, which integrates different factors like waste disposal, air and dust pollution, location of the landfill, water and noise pollution, fear of future health, property value, mosquitoes and rodent’s pollution, life in general in the community, etc.This study concludes that the residents living closer to the landfill sites are at higher health and environmental risks when compared to those living far away from the landfill sites. However, the landfill associated problems have helped the community living closer to the landfill to be more conscious and educated on environmental pollution. The health risk associated with landfill pollutants in this study shows that proper landfill management is very essential. Landfills should be located far away from residential houses and institutions to avoid certain health and environmental related risks.


Soft robotics is a branch of robotics that deals with mechatronics and electromechanical systems primarily made of soft materials. This paper presents a summary of a chronicle study of various soft robotic hand exoskeletons, with different electroencephalography (EEG)- and electromyography (EMG)-based instrumentations and controls, for rehabilitation and assistance in activities of daily living. A total of 45 soft robotic hand exoskeletons are reviewed. The study follows two methodological frameworks: a systematic review and a chronological review of the exoskeletons. The first approach summarizes the designs of different soft robotic hand exoskeletons based on their mechanical, electrical and functional attributes, including the degree of freedom, number of fingers, force transmission, actuation mode and control strategy. The second approach discusses the technological trend of soft robotic hand exoskeletons in the past decade. The timeline analysis demonstrates the transformation of the exoskeletons from rigid ferrous materials to soft elastomeric materials. It uncovers recent research, development and integration of their mechanical and electrical components. It also approximates the future of the soft robotic hand exoskeletons and some of their crucial design attributes. The emerging trend of soft robotics has stimulated the interest of engineers and researchers around the world to look into various applications, ranging from biomedical and rehabilitation to grasping and manipulation ,2. BiomiOne of the major lessons learned from these biostructures was the ability to form and adapt to complexly shaped bodies. This led to various developments such as: (1) an octopus-like robot for flexible manipulation ; (2) a wAnother important development in the emerging field of soft robotics is the use of pneumatic soft grippers for handling fragile objects such as an uncooked egg or an anesthetized mouse . These dThis new trend is especially interesting for biomedical and rehabilitation engineering applications as well, with the hand exoskeleton as one of the examples. A major shift from the use of hard to soft materials can be observed in some of the latest designs of hand exoskeletons, such as the Wyss Institute glove ,7,8, theUnlike a prosthetic hand, a hand exoskeleton is designed and built around the human hand; thus, it has to conform to the hand anatomy and its range of motion to minimize the wearer’s discomfort. More importantly, it has to be light and able to be put on easily so that the wearer can use it daily to perform basic activities. Hand exoskeletons have endured extensive research, primarily in the field of assistive and rehabilitative robotics, and have also been discussed from various perspectives ,30,31. SA chronological review was conducted of several renowned literature databases, i.e., Science Direct, PubMed, IEEE Xplorer, SciVal and Google Scholar, to identify the trend of soft robotics in hand exoskeletons from the year 2008 onward. The keywords used as the search entries to examine more categorical papers were ‘soft hand exoskeleton’ and ‘soft robotic hand exoskeleton’. The search results were further filtered with keywords like ‘rehabilitation’, ‘ADL’, ‘pneumatic’ and ‘tendon’. A set of inclusion and exclusion criteria was then applied to select the right literature.The following inclusion and exclusion criteria were used to funnel down the discrete knowledge that is vital for the systematic review and chronological review of the soft robotic hand exoskeleton.The study introduced and applied soft robotics technology for the development of a hand exoskeleton that included a wearable glove, actuator or bothThe study presented the mechanical or electrical aspect of the hand exoskeleton in at least three of the following attributes: actuation, active degrees of freedom (DOFs), finger movement, output force, range of motion (ROM), weight and functionalityThe hand exoskeleton had at least one soft robotic finger (3 degrees of freedom)The study presented a prototype or at least a design of the hand exoskeletonThe study was published in any language other than EnglishThe device used rigid or ferrous mechanical components for the glove design and linkagesThe device was used other than that for rehabilitation and assistance for ADLThe device was a prosthetic or anthropomorphic handA total of 65 literature works on soft robotic hand exoskeleton were found. However, only 45 devices were selected for the systematic review, because some designs were reported in several articles and used for different purposes. For example, the SNU research group presented their Exo-Glove Poly in ,21,22 anPrevious reviews revolved around short-term narration  and geneThe systematic review describes the merits and demerits of different exoskeletons based on their design attributes, such as ergonomics, complexity, instrumentation and actuation mode. It also discusses different design techniques that distinguish one soft exoskeleton from another. For this purpose, the attributes selected for comparison between different exoskeletons were based on quantitative results such as year of publication, mode of actuation, number of fingers, active degrees of freedom, output force and many other attributes.The chronological review investigates the adoption of soft robotics technology in the design of hand exoskeletons in the recent decade. Here, we review the evolution of the soft robotic hand exoskeleton systems and how the newer designs use soft robotics as a form of improvement from the previous studies. We examine the exoskeleton mechanical and electrical attributes and their functionalities based on the articles published from 2008 to 2017. It is hoped that by evaluating these elements annually, one can realize the importance of soft robotics in designing and developing better hand exoskeletons.Forty-five soft robotic hand exoskeletons were systematically reviewed based on the criteria described in Unlike prosthetics, hand exoskeletons are designed to actuate or mechanize the paralyzed human hand. In its early years, hand exoskeletons were made of rigid linkages. These linkages connected the exoskeleton with the finger, and the rotational axes of the joints were aligned with the human finger joints b. DespitSoft wearable gloves are usually made with fabric, plastic or silicone-based material. They can be designed as per the patient’s finger measurements. The fabric-based materials can be seen in the earlier designs of the SNU Exo-Glove , the gloA tendon/cable-driven mechanism is one of the most common actuation mechanisms embedded in the soft glove and generally requires more than one actuator. In the earlier designs, this mechanism had actuator units for each flexion and extension of the finger . The tenAnother common actuation mechanism is pneumatic based, in which most of the soft pneumatic actuators have strain limiting layers and/or fibers. The NUS glove , the MRCAn actuator is generally defined as having the ability to convert energy into motion. Actuators in a soft robotic hand exoskeleton mainly are comprised of tendon/cable–pulley and pneumatic/hydraulic systems. These actuators are usually placed on the dorsal side or on the sagittal plane of the finger to maximize the power transmission to the fingertip. In the pneumatic system, the air chamber is placed during the fabrication process. The soft actuator is then placed on the dorsal side of the fingers by either attaching it to the hand through a harness , stitching it to fabric-based material or gluing it to a glove . The mosGenerally, the control strategies of the hand exoskeletons can be divided into two categories: low-level and high-level control strategies. In the low-level control strategy, the controller addresses the physical parameters of the device such as force, torque and position . It usesAnother important aspect in designing a hand exoskeleton is the weight, which is also related to the reason behind choosing the actuating mechanism. As can be seen in Most of the hand exoskeletons designed for clinical research purposes are pneumatically-actuated , such asOne of the limitations of a soft pneumatic actuator is the delivered force or torque. The embedded pressure chamber requires high-pressure air to inflate and transmit the force to the end effector. While a driving force can be initiated, it is hard to control the holding force (gripping force). As the holding position requires continuous force, the pneumatic actuator has to continuously supply a specific amount of pressure to sustain the required gripping force . The powThe second part of this review paper is to investigate the evolution of soft robotic hand exoskeletons in the recent decade. It highlights the areas that have been investigated and the contributing factors in opening new avenues for further research. It also evaluates the trend and predicts how soft robotic hand exoskeletons may look in the future. Another important aspect of this review is to explore different parameters and variables used as the design criteria to develop hand exoskeletons.Sixty-five articles were carefully reviewed and are listed chronologically in One of the earliest works on soft robotic hand exoskeletons was the Power-Assist glove reported in  in 2008.In 2011, three articles were published. One of them was an exoskeleton that uses the tendon/cable–pulley mechanism , while tIn 2012, three studies were found, and all of them were tendon/cable-actuated soft exoskeletons ,40. One A five-finger cable-driven hand exoskeleton was proposed in 2013 . It has Three pneumatically-actuated exoskeletons were reported in 2014 ,44,45. OSince 2015, the development of soft robotic hand exoskeletons escalated. Thirteen studies were published, in which 10 of them were on pneumatic actuators ,53,54,55The research and development of soft robotic hand exoskeletons reached its peak in 2016. Fourteen articles were on pneumatically-actuated exoskeletons ,69,70,71In 2017, eight articles reported the use of pneumatic/hydraulic actuators ,49,76,77In order to understand the technological shift in the hand exoskeleton, a chronological analysis was conducted. This analysis is divided into three main areas of interest: mechanical, electrical and functionality of the soft exoskeleton. The electrical evolution of the soft robotic hand exoskeleton is depicted in Here, we summarize various soft robotic hand exoskeletons based on their merits and demerits and reviews the technological trend of these devices in the last decade, which includes 45 soft wearable exoskeletons along with their design criteria and basic properties. The systematic review describes the general trend and actuation mechanisms of the soft robotic hand exoskeleton. The summary shown in Up until now, rehabilitation purposes appear to have led the design and development of soft robotic hand exoskeletons. However, these soft wearable exoskeletons may be used for other functions as well. For example, the virtual reality control used in PneuGlove  allows e


Traumatic brain injury (TBI) commonly leads to development of seizures, accounting for approximately 20% of newly diagnosed epilepsy. Despite the high clinical significance, the mechanisms underlying the development of posttraumatic seizures (PTS) remain unclear, compromising appropriate management of these patients. Accumulating evidence suggest that thrombin, the main serine protease of the coagulation cascade, is involved in PTS genesis by mediating inflammation and hyperexcitability following blood brain barrier breakdown. In order to further understand the role of thrombin in PTS, we generated a combined mild TBI (mTBI) and status epilepticus mice model, by injecting pilocarpine to mice previously submitted to head injury. Interestingly, mTBI was able to reduce seizure onset in the pilocarpine animal model as well as increase the death rate in the treated animals. In turn, pilocarpine worsened spatial orientation of mTBI treated mice. Finally, thrombin activity as well as the expression of IL1-β and TNF-α was significantly increased in the mTBI-pilocarpine treated animals. In conclusion, these observations indicate a synergism between thrombin and mTBI in lowering seizure in the pilocarpine model and possibly aggravating inflammation. We believe that these results will improve the understanding of PTS pathophysiology and contribute to the development of more targeted therapies in the future. Traumatic brain injury (TBI) significantly increases the risk of seizures and is a major cause of intractable epilepsy , accountAlarmingly, PTS pathophysiology is yet to be fully understood, thus management of patients and outcomes are compromised. To better understand the underlying mechanism of PTS, prior studies first tried to identify a number of risk factors involved. A major one is TBI severity , especiaTo study epileptogenesis following mTBI, animal models were generated to replicate the complex implications of human mTBI and PTS. A commonly used model is the closed weight free drop mTBI rodent , which pin vivo synaptic disfunction and amnesia, effects that were reversed after the administration of thrombin inhibitors  and temporal lobe epilepsy (pilocarpine injection), we found that seizures intensity and death rate during SE were increased in the animals exposed to both treatments compared to those that experience a single one. In addition, the expression of both thrombin as well as inflammatory markers was higher in the former group than in the latter. We therefore conclude that our findings highlight the importance of thrombin in PTS pathophysiology, suggesting new directions in the management and treatment of these patients.The experiments were approved by the Institutional Animal Care and Use Committee of the Sheba Medical Center which obeys to national and NIH approved rules (ANIM 1089-17). The minimal number of animals was used and all efforts were made to minimize suffering. The study was carried out in 8 weeks old male C57BL/6J mice and mTBI was induced using a free weight drop concussive device as previously described . BrieflyOpen field was performed to evaluate cognitive function and anxiety in mice upon 24 h from low pilocarpine administration. This task takes advantage of rodents aversions to large, brightly lit, open, and unknown environment. Mice were placed in the middle of the open field apparatus consisted of square box (47 cm × 47 cm × 29 cm) and given 5 min to explore. Time in the center and crossing center frequencies were recorded and analyzed using EthoVision software (Noldus information technology). The mobility index was defined as: Total duration in the center/Crossing center frequency.Mice were anesthetized with pentobarbital (0.8 mg/kg) and rapidly decapitated for hippocampi dissections. Right hippocampus was dissected, and dorsal hippocampus used for thrombin activity. Thrombin enzymatic activity was measured using a fluorometric assay based on the cleavage rate of the synthetic substrate Boc-Asp (OBzl)-ProArg-AMC  and defined by the linear slope of the fluorescence intensity versus time, as previously described . The hipRight hemisphere hippocampi were dissected and prepared as described before . The RNAAdministration of pilocarpine in rodents is commonly used to model SE induction and subsequent mechanisms leading to epileptogenesis . SimilarPrimarily, we focused on the effect of both pilocarpine doses, and the consequent death that might result from those treatments. The experimental timeline included 50-gr weight drop followed by pilocarpine administration and seizure analysis (Pilocarpine treatment as well as exposure to mTBI are both known to affect cognitive functions, i.e., spatial orientation both in humans  and in aTo investigate the possible mechanisms involved in PTS using our mice model, we focused on thrombin which is known to play a key role both in epilepsy  and in mThrombin upregulation in the combined group can lead to harmful downstream effect, as thrombin has been pointed out as an important mediator of neuroinflammation and vascular disruption . To examIn this study, we evaluated the impact of mTBI on seizure outcomes in an animal model of seizures and epilepsy. While it is known that TBI significantly increases the risk of seizures and is a major cause of intractable epilepsy , no infoInterestingly, our data show that mTBI was able to affect the seizure onset in the pilocarpine animal model of SE. While a low dose of pilocarpine is usually associated to a lower seizure’s severity score, the combination of this treatment with mTBI resulted in a faster onset, higher severity of seizures compared to controls. This finding supports the possibility that mTBI could predispose the brain such that an additional low threshold stimulus, i.e., a low dose of pilocarpine, might result in a bigger effect than if the same stimulus would have been delivered alone. In other words, mTBI could act as a “conditioning stimulus”  and thusMortality due to seizures is also affected by a previous exposure to mTBI. This is an interesting observation which guarantees further exploration due to its potential clinical impact: could patients that have been exposed to mTBI and then developed epilepsy be more prone to SUDEP?The combination of both mTBI and seizures seems to affect spatial orientation as well. Indeed, while in mTBI, spatial orientation seems to be preserved, the advent of seizures worsens it. A possible explanation of this observation may lie in the hyperexcitable state of the hippocampal network following pilocarpine treatment. As the hippocampus is the major brain area involved in spatial orientation , upon seIn several, previous contributions, we have highlighted the role of thrombin, a serine protease, in the pathogenesis of epilepsy and mTBI . TherefoWhile additional experiments need to be performed, our observations point to an important link between mTBI and seizures. More studies are therefore needed in order to further evaluate this link for developing better therapeutical strategies for patients.The datasets generated for this study are available on request to the corresponding author.The animal study was reviewed and approved by the Institutional Animal Care and Use Committee of the Sheba Medical Center.ES-S supervised the project, conceived and planned the experiments, contributed to the analysis and interpretation of the results, and wrote the manuscript. MS conducted the experiments and data analysis and contributed to the writing of the manuscript. NM supervised the project, conceived and planned the experiments, gave a detailed interpretation of the results, and wrote the manuscript. KA wrote the manuscript. CP consulted regarding the project setting and results interpretation and reviewed the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.The handling editor declared a shared affiliation, though no other collaboration, with one of the authors, CP, at time of review.