What do surrogate safety metrics measure? Understanding driving safety as a continuum.

Road safety is an important public health issue; technology, policy, and educational interventions to prevent crashes are of significant interest to researchers and policymakers. In particular, there is significant ongoing research to proactively evaluate the safety of new technologies, including autonomous vehicles, before enough crashes occur to directly measure their impact. We analyze the distributional form of five diverse datasets that approximate motor vehicle safety incident severity, including one dataset of hard braking events that characterizes the severity of non-crash incidents. Our empirical analysis finds that all five datasets closely fit a lognormal distribution (Kolmogorov-Smirnov distance < 0.013; significance of loglikelihood ratio with other distributions < 0.000029). We demonstrate a linkage between two well-known but largely qualitative safety frameworks and the severity distributions observed in the data. We create a formal model of the Swiss Cheese Model (SCM) and show through analysis and simulations that this formalization leads to a lognormal distribution of the severity continuum of safety-critical incidents. This finding is not only consistent with the empirical data we examine, but represents a quantitative restatement of Heinrich's Triangle, another heretofore largely qualitative framework that hypothesizes that safety events of increasing severity have decreasing frequency. Our results support the use of more frequent, low-severity events to rapidly assess safety in the absence of less frequent, high-severity events for any system consistent with our formalization of SCM. This includes any complex system designed for robustness to single-point failures, including autonomous vehicles.

What is the yield of breast MRI in the assessment of palpable breast findings?

AIM: To examine the contribution of magnetic resonance imaging (MRI) to characterise palpable breast masses after conventional imaging was found to be non-contributory. MATERIALS AND METHODS: The breast MRI database was reviewed for studies performed between January 2010 and December 2015 for the clinical indication of palpable breast finding with negative standard imaging. Medical files were reviewed for demographic data, clinical information, radiology, and pathology reports. Benign versus malignant outcomes were determined at histopathology or a minimum of 12 month follow-up. RESULTS: Investigation of palpable breast finding was the clinical indication for 167 of 7,782 (2%) examinations. Thirty-two (19%) women in the study had positive MRI findings. Most (20, 63%) findings corresponded to the palpable area, resulting in three carcinomas being diagnosed. Only one carcinoma required MRI-guided biopsy for diagnosis. Eighteen women with negative MRI underwent ultrasound-guided biopsy from the palpable area, which resulted in a diagnosis of one carcinoma. One carcinoma was incidentally detected in another location. Within the present population, the sensitivity for detecting malignancy was 80%, specificity 78%, negative predictive value 99%, and positive predictive value 13%. CONCLUSIONS: Although cancer was found in four cases in the palpable area, the biopsy was directed using MRI in only one case. A new palpable finding with non-contributory standard imaging should prompt a needle-guided biopsy and not further evaluation using MRI.

Does change in microcalcifications with neoadjuvant treatment correlate with pathological tumour response?

AIM: To determine whether change in microcalcification density and extent after neoadjuvant treatment (NAT) can predict tumour response. MATERIALS AND METHODS: This single-institution, retrospective study included all women with breast cancer who underwent NAT between 1 January 2008 and 31 December 2014, and fulfilled the following criteria: mammography before NAT with pathological microcalcifications, mammography performed after NAT, and tumour resection at Tel-Aviv Sourasky Medical Center. Correlation was made between mammography features and clinicopathological information. RESULTS: Fifty-four patients met the inclusion criteria. Post-NAT, the number of calcifications remained stable in 30 (55.5%) patients, decreased in 23 (42.6%) patients, and increased in one (1.9%) patient. Patients with a decreased number of malignant calcifications post-NAT had higher rates of pathological complete response compared to patients with no change (59% versus 20%, p=0.009). Patients with triple negative and human epidermal growth factor receptor 2 (HER2) receptor subtypes had higher rates of decreased number of calcifications post-NAT (50% versus 35%) and pathological complete response (57% versus 11%, p=0.007) compared to patients with luminal receptor subtype. In addition, patients who received a combination of chemotherapy and biological treatment had more cases of decreased number of calcifications compared to patients who received chemotherapy alone (56% versus 39%). No significant correlation was observed between calcification change post-NAT and calcification morphology or distribution pattern. CONCLUSIONS: Patients with breast carcinoma and decreased number of pathological calcifications post-NAT had higher rates of pathological complete response compared to patients with no change in calcifications; however, a substantial number of patients with complete pathological response had no change in microcalcification distribution with treatment, questioning the need to completely excise all calcifications post-NAT.

Demographic and dietary predictors of urinary bisphenol A concentrations in adults in Israel.

BACKGROUND: To date, there is scarce data on levels of exposure to bisphenol A (BPA) in the general population in Israel and the region. The goal of the current study was to measure urinary levels of BPA in the general adult population in Israel and to determine the demographic and dietary predictors of exposure. METHODS: We recruited 249 individuals (ages 20-74) from five different regions in Israel. We collected urine samples and questionnaire data including detailed dietary data and analyzed urine samples for BPA concentrations. RESULTS: Eighty nine percent of the study population had urinary BPA concentrations equal to or above the level of quantification (0.3 µg/L). Median creatinine adjusted BPA urinary concentrations in the study population (2.3 µg/g) were slightly higher than those reported for the general population in the US (1.76 µg/g) and Canada (1.47 µg/g), and were comparable to those reported for the general population in Belgium (2.25 µg/g) and Korea (2.09 µg/g). BPA concentrations were higher in Jews compared to Arab and Druze (prevalence ratio (PR)=2.34; 95%CI 1.56-3.49), in individuals with higher education (PR=1.70, 1.11-2.62), in individuals consuming mushrooms (PR=2.08, 1.07-4.05), and in smokers (PR=1.43, 1.00-2.05). CONCLUSIONS: We found that the general adult population in Israel is widely exposed to BPA. Our findings on higher BPA levels in Jews compared to Arabs and Druze and in individuals with higher education highlights the fact that predictors of BPA exposure vary across populations.

Urinary concentrations of organophosphate pesticide metabolites in adults in Israel: demographic and dietary predictors.

Exposure to organophosphate pesticides (OPs) in agricultural and urban populations has been associated with a range of adverse health effects. The purpose of the current study was to estimate exposure to OPs in the general adult population in Israel and to determine dietary and demographic predictors of exposure. We measured six non-specific organophosphate pesticide metabolites (dialkyl phosphates) in urine samples collected from 247 Israeli adults from the general population. We collected detailed demographic and dietary data from these individuals, and explored associations between demographic and dietary characteristics and urinary dialkyl phosphate concentrations. OP metabolites were detectable in all urine samples. Concentrations of several dialkyl phosphate metabolites (dimethylphosphate, dimethylthiophosphate, diethylphosphate) were high in our study population relative to the general populations in the US and Canada and were comparable to those reported in 2010 in France. Total dialkyl phosphates were higher in individuals with fruit consumption above the 75th percentile. In a multivariate analysis, total molar dialkyl phosphate concentration increased with age and was higher in individuals with high income compared to individuals with the lowest income. Total diethyl metabolite concentrations were higher in females and in study participants whose fruit consumption was above the 75th percentile. In conclusion, we found that levels of exposure to OP pesticides were high in our study population compared to the general population in the US and Canada and that intake of fruits is an important source of exposure.

Urinary concentrations of environmental contaminants and phytoestrogens in adults in Israel.

BACKGROUND: The Ministry of Health Biomonitoring Study estimated exposure of individuals in the Israeli population to bisphenol A (BPA), organophosphate (OP) pesticides, phthalates, cotinine, polycyclic aromatic hydrocarbons (PAHs), and the phytoestrogenic compounds genistein and daidzein. METHODS: In 2011, 250 individuals (ages 20-74) were recruited from five different regions in Israel. Urine samples were collected and questionnaire data were obtained, including detailed dietary data (food frequency questionnaire and 24hour recall). Urinary samples were analyzed for BPA, OP metabolites (dialkyl phosphates), phthalate metabolites, cotinine, PAH metabolites, genistein, and daidzein. RESULTS AND DISCUSSION: BPA urinary concentrations were above the limit of quantification (LOQ) in 89% of the samples whereas urinary concentrations of phthalate metabolites were above the LOQ in 92-100% of the samples. PAH metabolites were above the LOQ in 63-99% of the samples whereas OP metabolites were above the LOQ in 44-100% of the samples. All non-smoking participants had detectable levels of cotinine in their urine; 63% had levels above the LOQ, and the rate of quantification was high compared to the general non-smoking population in Canada. Median creatinine adjusted concentrations of several OP metabolites (dimethyl phosphate, dimethyl thiophosphate) were high in our study population compared to the general US and Canadian populations. Median creatinine adjusted urinary BPA concentrations in the study population were comparable to those in Belgium and Korea; higher than those reported for the general US, German, and Canadian populations; and very low compared to health-based threshold values. Phthalate concentrations were higher in our study population compared to the general US population but values were very low compared to health-based threshold values. Median creatinine adjusted PAH concentrations were generally comparable to those reported for the general US population; median creatinine adjusted daidzein concentrations were high in our population compared to the general US population whereas genistein concentrations were comparable. CONCLUSIONS: We interpreted observed urinary contaminant levels observed in our study by comparing values with health-based threshold values and/or values from international human biomonitoring studies. Using this data interpretation scheme, we identified two contaminants as being of potential public health concern and high priority for public health policy intervention: environmental tobacco smoke (ETS) and OP pesticides. We used the data collected in this study to support public health policy interventions. We plan to conduct a follow-up biomonitoring study in 2015 to measure ETS and OP exposure in the general population in Israel, to evaluate the effectiveness of relevant policy interventions.

Ambient temperature and congenital heart defects.

STUDY QUESTION: Does maternal exposure during pregnancy to higher ambient temperature increase the risk of congenital heart defects (CHDs)? SUMMARY ANSWER: Significant associations were found between maternal exposure during pregnancy to higher ambient temperature and CHDs risk especially during the cold season. WHAT IS KNOWN ALREADY: From rodents to non-human primates, a teratogenic effect of hyperthermic insult has been demonstrated. There are fewer data regarding the effect on the human fetus and specifically the association between maternal exposures during pregnancy to higher ambient temperature and CHDs. STUDY DESIGN, SIZE, DURATION: This population registry-based cohort study included 135 527 live and stillbirths in the Tel-Aviv region of Israel in 2000-2006. PARTICIPANTS/MATERIALS, SETTING, METHODS: Two clinical diagnostic groups of isolated cardiac defects (atrial septal defects and ventricular septal defects: n = 542 and 481, respectively) and one group of multiple cardiac defects (defined by the presence of two or more cardiac malformations, n = 607) were studied. Temperature measurements were constructed from ambient stations and used to assess the impact of maternal exposure to average ambient temperature and extreme heat events (daily average temperature above the 90th percentile) during Weeks 3-8 of pregnancy on risk of CHDs. Logistic models, adjusted for sociodemographic covariates, were used to evaluate the associations between temperature and CHDs. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, we found no significant associations between ambient temperature and CHDs throughout the year, with one exception for multiple CHDs. After stratifying by season of conception, continuous exposure to average ambient temperature and maximum peak temperature (1°C increase) during the cold season increased the risk for multiple CHDs [odds ratio (OR) 1.05, 95% confidence interval (CI): 1.00, 1.10 and OR 1.03, 95% CI: 1.01, 1.05, respectively]. A 1-day increase in extreme heat events increased the risk for multiple CHDs (OR 1.13, 95% CI: 1.06, 1.21) and also for isolated atrial septal defects (OR 1.10, 95% CI: 1.02, 1.19). LIMITATIONS, REASONS FOR CAUTION: Information both on CHD cases and on ambient temperature was based on registries and it is possible that this may cause some misclassification. In urban areas, pregnant women may be exposed to higher temperatures than recorded by ambient monitors because of the 'heat island effect'. Furthermore, data for the amount of time spent indoors were unavailable and this could have resulted in exposure misclassification. WIDER IMPLICATIONS OF THE FINDINGS: The findings are important within the context of global climate change, which may have implications for public health in countries with mild winters and hot summers. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the Israeli Ministry of Environmental Protection (research grant-7-2-7) and by the Environment and Health Fund (PhD Fellowship Program). There are no competing interests.

Apparent life-threatening events in infants and homeopathy: an alternative explanation.

BACKGROUND: A recent report showed increased frequency of apparent life-threatening events (ALTEs) in infants treated with the homeopathic medication GaliCol-Baby (GCB). The premise was that the ALTEs resulted from toxic effects of the drug's components. We examine an alternative explanation. METHOD: The toxicological literature was searched for known reactions to the various GCB components, noting doses and reported symptoms. Dosage quantities and severity of reaction to the GCB were ranked independently by two groups of physicians, and a dose-response curve was generated. Reported toxic doses and symptoms were compared with those of the GCB series. The homeopathic literature was searched as well to determine the propensity of the GCB components to cause ALTE symptoms, when given in homeopathic doses to healthy volunteers (proving). RESULTS: Doses ingested in the GCB series were 10-13 orders of magnitude smaller than those reported to cause toxic reactions in humans. There was poor correlation between symptoms with GCB and toxic profiles of the components. A nonsignificant, inverse relationship between dose and severity of reaction was observed. Conversely, four GCB components (in homeopathic doses) had a high propensity to produce at least one of five symptoms which define ALTE, two of which had intermediate to high propensity to produce three symptoms. CONCLUSIONS: It is unlikely that the ALTE following ingestion of GCB was a toxic reaction to any of the drug's component. Homeopathic theory may explain this linkage, though further research is needed to understand the pathogenic effects of highly diluted homeopathic compounds.

Enhanced stress reactivity in nitric oxide synthase type 2 mutant mice: findings in support of astrocytic nitrosative modulation of behavior.

Alterations of nitric oxide (NO) metabolism in the brain have been associated with modifications of stress-related behavior in animal models. It has been generally assumed that these behavioral changes are due to the neuronal nitrosative activity. On the other hand, glial NO production has been demonstrated mainly as a slow reaction to brain insults through the activity of an inducible nitric oxide synthase (NOS) isoform (NOS2). Recently we uncovered increased NOS activity in astrocytes of mice with a NOS2 mutation. Interestingly, these mice revealed a behavioral phenotype suggestive of increased susceptibility to stress. In the present study we investigated the responses of these mutants to stress by exposing them to predator scent. Seven days later, mutant mice exhibited significantly higher anxiety-like behavior in the elevated-plus maze, increased acoustic startle responses, and higher plasma corticosterone levels compared with their controls. Systemic administration of a NOS inhibitor prior to the stress exposure reversed these stress-related effects without affecting controls' behavior. These findings are in agreement with previous studies showing an association between increased NO levels and enhanced anxiety-like responses. In addition, mutant mice performed better in the Morris water maze prior to stress exposure, but the two animal groups performed alike in an object-recognition test. Taken together, our results suggest the involvement of astrocytic-derived NO in modulating behavior.

Comparative properties of excitatory and inhibitory inter-laminar neocortical axons.

In recent years it has become increasingly clear that variations in voltage-gated channels, as well as highly diverse geometrical properties, shape the way axons conduct action potentials to their terminals. Numerous cell types in the mammalian neocortex form a dense network of connections, and the properties of their axons may have an effect on the processing performed by this network. We studied the conduction properties of local, inter-laminar axons emanating from regular-spiking (RS) pyramidal neurons and Martinotti type inhibitory neurons (MCs) in layer 5 of the mouse barrel neocortex by comparing the patterns of their antidromic activation from layer 1. Both types of axons had similarly slow conduction velocities ( approximately 0.3 m/s), compatible with thin unmyelinated fibers. In addition, in both types of neurons, subthreshold changes of the somatic membrane potential affected the stimulus threshold for evoking an antidromic spike in layer 1, a distance of 600-800 microm. However, the axons differed considerably in their antidromic activation profiles. 1) The antidromic latency in RS neurons was highly consistent while some MCs display considerable activation-latency jitter; 2) RS neurons displayed a steeper increase in excitability to repeated 40 Hz stimulation; 3) RS neurons displayed a sharp, step-like antidromic activation threshold to both somatic voltage and stimulus intensity, while MCs displayed a gradual recruitment pattern. Morphological differences in the branching pattern of the two types of neurons may account for some of these distinctions. These results suggest differences among excitatory and inhibitory neocortical neurons in the computational tasks of their local axons.

Effect of religious observance on infants' sleep position in the Jewish population.

OBJECTIVES: To describe the effect of the level of religiousness on infants' sleep position in the Jewish population. METHODS: A longitudinal telephone survey of randomly selected 608 2-month-old Jewish infants repeated at 4 and 6 months. Results were analyzed versus the four levels of Jewish religion observance. RESULTS: A significant correlation was found between the level of religious practice and sleep position (P < or = 0.002). 56.8% (50/88) of ultra-orthodox parents put their babies to sleep in the non-prone position, compared with 79% (411/520) in the other three groups (P < 0.001). Non-prone sleeping decreased when infants grew. Higher parity correlated with the level of religiousness and with prone sleeping in religious families (OR = 1.15, 95% CI 1.00-1.33, P < 0.001). CONCLUSIONS: Jews and especially the ultra-orthodox families comply significantly less with recommendations to avoid prone sleeping. Specific measures may be required in this population that rely more on personal experience and belief than on health care provider advice.

Association of parental consanguinity with congenital malformations among Arab newborns in Jerusalem.

The aim of this work was to determine the impact of parental consanguinity on congenital malformations in a mixed urban and rural Arab community in Jerusalem, Israel. Arab mothers admitted to four hospitals in west Jerusalem were interviewed after delivery. Demographic and obstetric data were recorded. Neonatal data were extracted from the medical records of the nursery. When malformations were suspected, a 4- to 10-month follow up was achieved for confirming the diagnosis. Of 561 infants, 253 (45%) were born to consanguineous couples. The incidence of major congenital malformations in the offspring was 8.7, 7.1 and 2.6% in cases of first cousins, all consanguineous, and non-consanguineous couples, respectively. No association was found between parental consanguinity and prematurity (p = 0.357) or low birth weight (p = 0.589). Parental consanguinity was also associated with an increased incidence of death in previous siblings (p < 0.000). The increased incidence of congenital malformations and infant mortality in cases of inbreeding prompt the necessity of establishing programs to avoid these complications in the offspring.

Dietary folate and the incidence and prevention of neural tube defects: a proposed triple intervention approach in Israel.

The efficacy of folic acid in the prevention of neural tube defects depends on whether it is administered to women during the period surrounding conception. Optimizing the compliance of women at this critical time is a public health challenge. We assess the need for formulation of public health policy in Israel aimed at enhancing folate intake by women, examine policy implementation strategies, and review policy options regarding the approaches to enhance folic acid intake.

Thalamocortical synaptic connections: efficacy, modulation, inhibition and plasticity.

The thalamic input to the neocortex is communicated by glutamatergic synapses. The properties and organization of these synapses determine the primary level of cortical processing. Similar to intracortical synapses, both AMPA and NMDA receptors in young and mature animals mediate thalamocortical transmission. Kainate receptors participate in thalamocortical transmission during early development. The shape of thalamocortical synaptic potentials is similar to the shape of intracortical potentials. On the other hand, thalamocortical synapses have on average a higher release probability than intracortical synapses, and a much higher number of release sites per axon. As a result, the transmission of each thalamocortical axon is significantly more reliable and efficient than most intracortical axons. Thalamic axons specifically innervate a subset of inhibitory cells, to create a strong and secure feed-forward inhibitory pathway. Thalamocortical connections display many forms of synaptic plasticity in the first postnatal week, but not afterwards. The implications of the functional organization of thalamocortical synapses for neocortical processing are discussed.

Five decades of trends in anemia in Israeli infants: implications for food fortification policy.

OBJECTIVE: To describe the secular trends in the prevalence rates of iron-deficiency anemia (IDA) in infants in Israel, identify population group differences and assess the effectiveness of the 1985 Public Health directives on iron supplementation and avoidance of cow's milk in the first year of life. DESIGN: A systematic analysis of published and unpublished cross-sectional studies. METHODS: IDA rates in 1-y-old infants between 1946 and 1997 were assessed from published papers and reports. Rates for Arab infants were available from 1984. Data on routine hemoglobin tests on 1-y-old infants for Arabs and Jews separately were obtained from four health districts for the period 1987 to 1997. Analyses were done for the periods prior to and following the Public Health directives. RESULTS: The prevalence of IDA in Jewish infants declined from 68% in 1946 to 50% in 1985 at an average annual rate of -1.43%. Following the iron supplementation directives, the average annual rate of decline increased to -4.0% and reached a prevalence of about 11% in 1996. IDA rates in Arab infants declined by an annual average of -3.7%, and were consistently almost twice as high as for Jewish infants. CONCLUSIONS: Despite the contribution of the iron supplementation program to the reduction in TDA, the persistently high rates indicate inadequate iron content in the diet. This emphasizes the important role of a national food fortification program, using staple foods commonly consumed.

[Community health services for adolescents in Israel--challenges for the next decade].

Adolescent health issues have become an increasingly important challenge for public health in Israel. Meeting this challenge is difficult because of the special needs of this age group, inadequate training of health professionals, reimbursement policies, and the need for multisectorial cooperation. The past decade has seen a proliferation of community-based health services designed to meet the needs of adolescents. These services are of four basic types: 1) primary care clinics; 2) school health services; 3) multi-disciplinary adolescent health centers; and 4) other services, including reproductive health clinics, mental health and eating disorder units, and informal youth counseling centers. This development has taken place without systematic public health planning, including prioritization and the design of an orderly, integrative network of primary and referral services. We present national health planning goals to meet these challenges. These goals include: 1) defining the roles of each health care sector; 2) providing professional training to meet these roles; 3) facilitating the development of a rational system of community-based health services; and 4) offering a more equitable distribution of services. Implementing these goals should aid in better meeting the unique health needs Israel's adolescent population.

Poison exposure in children before Passover.

BACKGROUND: Extensive cleaning of homes in Israel before Passover may result in increased exposure of children to cleaning substances. OBJECTIVES: To evaluate the potential danger of Passover cleaning to children, and to study the risk factors in order to identify areas for prevention. METHODS: All cases of poison exposure in Jewish and Arab children under the age of 15 years reported to the Israel Poison Information Center during 1990-95 (n = 5,583) were analyzed for the 6 weeks before and 6 weeks after Passover. Poison exposures in Jewish children < 15 years old were studied in seven pediatric emergency rooms for the 2 weeks before and 6 weeks after Passover (n = 123). RESULTS: The IPIC data showed a highly significant 38% increase in the average weekly poison exposure rate for the 2 weeks before Passover compared with the remaining 10 weeks. Data recorded by the pediatric emergency rooms showed a twofold increase in cleaning substance poisoning during the 2 weeks before Passover compared with the following 6 weeks. The rise in exposures to cleaning substances was observed among children from secular, religious and ultra-orthodox families. In these exposures, the substance was found in open containers in 70% of cases. CONCLUSIONS: The extensive cleaning of homes among Jewish families in preparation for Passover poses the danger to young children of cleaning substance poisoning. Increasing public awareness, closer observation of children, and keeping these substances in closed containers should increase children's safety during this annual cleaning.