Pfizer COVID19 vaccine is not associated with acute cardiovascular events excluding myocarditis- a national self-controlled case series study.

BACKGROUND: Despite publications assuring no increased risk for acute cardiovascular events (excluding myocarditis) and sudden death following administration of COVID19 vaccines, these issues still stir much public ado. We assessed the risk for acute cardiovascular events that require hospitalization (excluding myocarditis) and for mortality in the short-term following administration of the second dose of the Pfizer COVID19 vaccine in Israel. METHODS: Using a self-controlled case series (SCCS) study design and national databases, all second-dose vaccinees, who had not been diagnosed with COVID19 and who had an acute cardiovascular event (acute myocardial infarction/acute stroke/acute thromboembolic event) that required hospitalization in the 60 days following vaccine administration between Jan 11th, 2021 and Oct 31st 2021, were included. A similar analysis was carried out for mortality. The first 30 days following vaccination were defined as risk period while the next 30 days were defined as control period. The probability for an event between these periods was compared using a conditional logistic regression model, accounting for sex, age group, background morbidity and seasonal risk. RESULTS: Out of 5,700,112  second dose vaccinees, 4,163 had an acute cardiovascular event in the 60 days following vaccine administration. Following exclusion of 106 due to technical considerations, 1,979 events occurred during the risk period and 2,078 during the control period: Odds ratio, OR = 0.95, 95% confidence interval, CI 0.90-1.01, p = 0.12. Adjusted OR was similar (OR = 0.88, 95%CI 0.72-1.08). Stratifying by age showed no increased risk in any age group. Mortality assessment indicated low number of events in both periods. These results were consistent in sensitivity analyses. CONCLUSIONS: There was no increased risk for acute cardiovascular events (excluding myocarditis) in the risk period compared to the control period following administration of the second dose of Pfizer COVID19 vaccine. Mortality data raised no concerns either, but may have been biased.

Age-dependent seasonality in the incidence of stroke: A 21-year population-based study.

INTRODUCTION: Seasonality in the incidence of stroke has been examined in numerous studies, yet data on whether it differs with age are limited. To fill this gap, we utilized a largescale dataset from Israel. PATIENTS AND METHODS: We retrieved data of all hospitalizations for ischemic stroke (IS), transient ischemic attack (TIA) and intra cerebral hemorrhage (ICH) from 2000 to 2020. We maintained separate datasets for IS/TIA and ICH, divided into five age groups: 18-49, 50-59, 60-69, 70-79, and 80+. We modeled the monthly incidence using a generalized additive model. The seasonal effect was defined by the rate ratio (RR) of each month compared to the annual mean. RESULTS: The analysis included 317,586 and 23,789 events of IS/TIA and ICH respectively. We found an interaction between age and seasonality, accounting for a phase shift with age in the seasonal pattern of IS/TIA incidence. For cases under 70 years, the peak was during summertime and the RRs increased with decreasing age, reaching 1.11 (95% CI 1.09-1.13) at the youngest age group. In contrast, among the elderly, a winter peak was observed and the RRs increased with age to 1.07 (95% CI 1.06-1.08) at the oldest age group. For ICH, a winter/autumn peak was identified and the RRs increased with age to 1.20 (95% CI 1.16-1.24). CONCLUSIONS: Our finding of age-dependent seasonal patterns in the occurrence of stroke, suggests closer monitoring of cardiovascular risk factors during wintertime among elderly individuals. The mechanism governing the seasonal phase shift with age in IS/TIA incidence, requires further investigation.

Longitudinal bidirectional link between socioeconomic position and health: a national panel survey analysis.

BACKGROUND: Health inequities can stem from socioeconomic position (SEP) leading to poor health (social causation) or poor health resulting in lower SEP (health selection). We aimed to examine the longitudinal bidirectional SEP-health associations and identify inequity risk factors. METHODS: Longitudinal Household Israeli Panel survey participants (waves 1-4), age ≥25 years, were included (N=11 461; median follow-up=3 years). Health rated on a 4-point scale was dichotomised as excellent/good and fair/poor. Predictors included SEP parameters (education, income, employment), immigration, language proficiency and population group. Mixed models accounting for survey method and household ties were used. RESULTS: Examining social causation, male sex (adjusted OR 1.4; 95% CI 1.1 to 1.8), being unmarried, Arab minority (OR 2.4; 95% CI 1.6 to 3.7, vs Jewish), immigration (OR 2.5; 95% CI 1.5 to 4.2, reference=native) and less than complete language proficiency (OR 2.22; 95% CI 1.50 to 3.28) were associated with fair/poor health. Higher education and income were protective, with 60% lower odds of subsequently reporting fair/poor health and 50% lower disability likelihood. Accounting for baseline health, higher education and income were associated with lower likelihood of health deterioration, while Arab minority, immigration and limited language proficiency were associated with higher likelihood. Regarding health selection, longitudinal income was lower among participants reporting poor baseline health (85%; 95% CI 73% to 100%, reference=excellent), disability (94%; 95% CI 88% to 100%), limited language proficiency (86%; 95% CI 81% to 91%, reference=full/excellent), being single (91%; 95% CI 87% to 95%, reference=married), or Arab (88%; 95% CI 83% to 92%, reference=Jews/other). CONCLUSION: Policy aimed at reducing health inequity should address both social causation (language, cultural, economic and social barriers to good health) and health selection (protecting income during illness and disability).

Durability of Immune Response After COVID-19 Booster Vaccination and Association With COVID-19 Omicron Infection.

Importance: The BNT162b2 two-dose vaccine (BioNTech/Pfizer) has high effectiveness that wanes within several months. The third dose is effective in mounting a significant immune response, but its durability is unknown. Objective: To compare antibody waning after second and third doses and estimate the association of antibody kinetics with susceptibility to infection with the Omicron variant of SARS-CoV-2. Design, Setting, and Participants: In a prospective longitudinal cohort study in a tertiary medical center in Israel, health care workers who received the BNT162b2 vaccine were followed up monthly for IgG and neutralizing antibody levels. Linear mixed models were used to compare antibody titer waning of second and third doses and to assess whether antibody dynamics were associated with Omicron transmission. Avidity, T cell activation, and microneutralization of sera against different variants of concern were assessed for a subgroup. Exposure: Vaccination with a booster dose of the BNT162b2 vaccine. Main Outcomes and Measures: The primary outcome was the rate of antibody titer change over time, and the secondary outcome was SARS-CoV-2 Omicron variant infection, as confirmed by reverse transcriptase-polymerase chain reaction. Results: Overall, 4868 health care workers (mean [SD] age, 46.9 [13.7] years; 3558 [73.1%] women) and 3972 health care workers (mean [SD] age, 48.5 [14.1] years; 996 [74.9%] women) were followed up for 5 months after their second and third vaccine doses, respectively. Waning of IgG levels was slower after the third compared with the second dose (1.32%/d [95% CI, 1,29%/d to 1.36%/d] vs 2.26% [95% CI, 2.13%/d 2.38%/d]), as was waning of neutralizing antibody levels (1.32%/d [95% CI, 1.21%/d to 1.43%/d] vs 3.34%/d [95% CI, 3.11%/d to 3.58%/d]). Among 2865 health care workers assessed for Omicron incidence during an additional 2 months of follow-up, lower IgG peak (ratio of means 0.86 [95% CI, 0.80-0.91]) was associated with Omicron infection, and among participants aged 65 years and older, faster waning of IgG and neutralizing antibodies (ratio of mean rates, 1.40; [95% CI, 1.13-1.68] and 3.58 [95% CI, 1.92-6.67], respectively) were associated with Omicron infection. No waning in IgG avidity was observed 112 days after the third dose. Live neutralization of Omicron was lower compared with previous strains, with a geometric mean titer at the peak of 111 (95% CI, 75-166), compared with 942 (95% CI, 585-1518) for WT, 410 (95% CI, 266-634) for Delta; it demonstrated similar waning to 26 (95% CI, 16-42) within 4 months. Among 77 participants tested for T cell activity, mean (SD) T cell activity decreased from 98 (5.4) T cells/106 peripheral blood mononuclear cells to 59 (9.3) T cells/106 peripheral blood mononuclear cells. Conclusions and Relevance: This study found that the third vaccine dose was associated with greater durability than the second dose; however, Omicron was associated with greater resistance to neutralization than wild type and Delta variants of concern. Humoral response dynamics were associated with susceptibility to Omicron infection.

Superior immunogenicity and effectiveness of the third compared to the second BNT162b2 vaccine dose.

As the effectiveness of a two-dose messenger RNA (mRNA) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine regimen decreases with time, a third dose has been recommended. Here, we assessed immunogenicity, vaccine effectiveness and safety of the third BNT162b2 vaccine dose in a prospective cohort study of 12,413 healthcare workers (HCWs). Anti-RBD immunoglobulin G (IgG) levels were increased 1.7-fold after a third dose compared with following the second dose. Increased avidity from 61.1% (95% confidence interval (CI), 56.1-66.7) to 96.3% (95% CI, 94.2-98.5) resulted in a 6.1-fold increase in neutralization titer. Peri-infection humoral markers of 13 third-dose Delta variant of concern (VOC) breakthrough cases were lower compared with 52 matched controls. Vaccine effectiveness of the third dose relative to two doses was 85.6% (95% CI, 79.2-90.1). No serious adverse effects were reported. These results suggest that the third dose is superior to the second dose in both quantity and quality of IgG antibodies and safely boosts protection from infection.

Prevalence of Antibiotic Tolerance and Risk for Reinfection Among Escherichia coli Bloodstream Isolates: A Prospective Cohort Study.

BACKGROUND: Tolerance is the ability of bacteria to survive transient exposure to high concentrations of a bactericidal antibiotic without a change in the minimal inhibitory concentration, thereby limiting the efficacy of antimicrobials. The study sought to determine the prevalence of tolerance in a prospective cohort of E. coli bloodstream infection and to explore the association of tolerance with reinfection risk. METHODS: Tolerance, determined by the Tolerance Disk Test (TDtest), was tested in a prospective cohort of consecutive patient-unique E. coli bloodstream isolates and a collection of strains from patients who had recurrent blood cultures with E. coli (cohorts 1 and 2, respectively). Selected isolates were further analyzed using time-dependent killing and typed using whole-genome sequencing. Covariate data were retrieved from electronic medical records. The association between tolerance and reinfection was assessed by the Cox proportional-hazards regression and a Poisson regression models. RESULTS: In cohort 1, 8/94 isolates (8.5%) were tolerant. Using multivariate analysis, it was determined that the risk for reinfection in the patients with tolerant index bacteremia was significantly higher than for patients with a nontolerant strain, hazard ratio, 3.98 (95% confidence interval, 1.32-12.01). The prevalence of tolerance among cohort 2 was higher than in cohort 1, 6/21(28.6%) vs 8/94 (8.5%), respectively (P = .02). CONCLUSIONS: Tolerant E. coli are frequently encountered among bloodstream isolates and are associated with an increased risk of reinfection. The TDtest appears to be a practicable approach for tolerance detection and could improve future patient management.

Similarity of Protection Conferred by Previous SARS-CoV-2 Infection and by BNT162b2 Vaccine: A 3-Month Nationwide Experience From Israel.

The worldwide shortage of vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection while the pandemic still remains uncontrolled has led many countries to the dilemma of whether or not to vaccinate previously infected persons. Understanding the level of protection conferred by previous infection compared with that of vaccination is important for policy-making. We analyzed an updated individual-level database of the entire population of Israel to assess the protection provided by both prior infection and vaccination in preventing subsequent SARS-CoV-2 infection, hospitalization with coronavirus disease 2019 (COVID-19), severe disease, and death due to COVID-19. Outcome data were collected from December 20, 2020, to March 20, 2021. Vaccination was highly protective, with overall estimated effectiveness of 94.5% (95% confidence interval (CI): 94.3, 94.7) for documented infection, 95.8% (95% CI: 95.2, 96.2) for hospitalization, 96.3% (95% CI: 95.7, 96.9) for severe illness, and 96.0% (95% CI: 94.9, 96.9) for death. Similarly, the overall estimated level of protection provided by prior SARS-CoV-2 infection was 94.8% (95% CI: 94.4, 95.1) for documented infection, 94.1% (95% CI: 91.9, 95.7) for hospitalization, and 96.4% (95% CI: 92.5, 98.3) for severe illness. Our results should be considered by policy-makers when deciding whether or not to prioritize vaccination of previously infected adults.

Coeliac plexus radiosurgery for pain management in patients with advanced cancer : study protocol for a phase II clinical trial.

INTRODUCTION: Pancreatic cancer is characterised by severe mid-back and epigastric pain caused by tumour invasion of the coeliac nerve plexus. This pain is often poorly managed with standard treatments. This clinical trial investigates a novel approach in which high-dose radiation (radiosurgery) is targeted to the retroperitoneal coeliac plexus nerve bundle. Preliminary results from a single institution pilot trial are promising: pain relief is substantial and side effects minimal. The goals of this study are to validate these findings in an international multisetting, and investigate the impact on quality of life and functional status among patients with terminal cancer. METHODS AND ANALYSIS: A single-arm prospective phase II clinical trial. Eligible patients are required to have severe coeliac pain of at least five on the 11-point BPI average pain scale and Eastern Cooperative Oncology Group performance status of two or better. Non-pancreatic cancers invading the coeliac plexus are also eligible. The intervention involves irradiating the coeliac plexus using a single fraction of 25 Gy. The primary endpoint is the complete or partial pain response at 3 weeks. Secondary endpoints include pain at 6 weeks, analgesic use, hope, qualitative of life, caregiver burden and functional outcomes, all measured using validated instruments. The protocol is expected to open at a number of cancer centres across the globe, and a quality assurance programme is included. The protocol requires that 90 evaluable patients" be accrued, based upon the assumption that a third of patients are non-evaluable (e.g. due to death prior to 3-weeks post-treatment assessment, or spontaneous improvement of pain pre-treatment), it is estimated that a total of 120 patients will need to be accrued. Supported by Gateway for Cancer Research and the Israel Cancer Association. ETHICS AND DISSEMINATION: Ethic approval for this study has been obtained at eight academic medical centres located across the Middle East, North America and Europe. Results will be disseminated through conference presentations and peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT03323489.

BNT162b2 vaccine effectiveness was marginally affected by the SARS-CoV-2 beta variant in fully vaccinated individuals.

OBJECTIVE: To evaluate the effectiveness of the Pfizer BNT162b2 vaccine against the SARS-Cov-2 Beta variant. STUDY DESIGN AND SETTING: Israel's mass vaccination program, using two doses of the Pfizer BNT162b2 vaccine, successfully curtailed the Alpha variant outbreak during winter 2020-2021, However, the virus may mutate and partially evade the immune system. To monitor this, sequencing of selected positive swab samples of interest was initiated. Comparing vaccinated with unvaccinated PCR positive persons, we estimated the odds ratio for a vaccinated case to have the Beta vs. the Alpha variant, using logistic regression, controlling for important confounders. RESULTS: There were 19 cases of Beta variant (3.2%) among those vaccinated more than 14 days before the positive sample and 79 (3.4%) among the unvaccinated. The estimated odds ratio was 1.26 (95% CI: 0.65-2.46). Assuming the effectiveness against the Alpha variant to be 95%, the estimated effectiveness against the Beta variant was 94% (95% CI: 88%-98%). CONCLUSION: Despite concerns over the Beta variant, the BNT162b2 vaccine seemed to provide substantial immunity against both the Beta and the Alpha variants. From 14 days following the second vaccine dose, the effectiveness of BNT162b2 vaccine was at most marginally affected by the Beta variant.

Waning Immune Humoral Response to BNT162b2 Covid-19 Vaccine over 6 Months.

BACKGROUND: Despite high vaccine coverage and effectiveness, the incidence of symptomatic infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been increasing in Israel. Whether the increasing incidence of infection is due to waning immunity after the receipt of two doses of the BNT162b2 vaccine is unclear. METHODS: We conducted a 6-month longitudinal prospective study involving vaccinated health care workers who were tested monthly for the presence of anti-spike IgG and neutralizing antibodies. Linear mixed models were used to assess the dynamics of antibody levels and to determine predictors of antibody levels at 6 months. RESULTS: The study included 4868 participants, with 3808 being included in the linear mixed-model analyses. The level of IgG antibodies decreased at a consistent rate, whereas the neutralizing antibody level decreased rapidly for the first 3 months with a relatively slow decrease thereafter. Although IgG antibody levels were highly correlated with neutralizing antibody titers (Spearman's rank correlation between 0.68 and 0.75), the regression relationship between the IgG and neutralizing antibody levels depended on the time since receipt of the second vaccine dose. Six months after receipt of the second dose, neutralizing antibody titers were substantially lower among men than among women (ratio of means, 0.64; 95% confidence interval [CI], 0.55 to 0.75), lower among persons 65 years of age or older than among those 18 to less than 45 years of age (ratio of means, 0.58; 95% CI, 0.48 to 0.70), and lower among participants with immunosuppression than among those without immunosuppression (ratio of means, 0.30; 95% CI, 0.20 to 0.46). CONCLUSIONS: Six months after receipt of the second dose of the BNT162b2 vaccine, humoral response was substantially decreased, especially among men, among persons 65 years of age or older, and among persons with immunosuppression.

BNT162b2 COVID-19 vaccine and correlates of humoral immune responses and dynamics: a prospective, single-centre, longitudinal cohort study in health-care workers.

BACKGROUND: Concurrent with the Pfizer-BioNTech BNT162b2 COVID-19 vaccine roll-out in Israel initiated on Dec 19, 2020, we assessed the early antibody responses and antibody kinetics after each vaccine dose in health-care workers of different ages and sexes, and with different comorbidities. METHODS: We did a prospective, single-centre, longitudinal cohort study at the Sheba Medical Centre (Tel-Hashomer, Israel). Eligible participants were health-care workers at the centre who had a negative anti-SARS-CoV-2 IgG assay before receiving the first dose of the intramuscular vaccine, and at least one serological antibody test after the first dose of the vaccine. Health-care workers with a positive SARS-CoV-2 PCR test before vaccination, a positive anti-SARS-CoV-2 IgG serology test before vaccination, or infection with COVID-19 after vaccination were excluded from the study. Participants were followed up weekly for 5 weeks after the first vaccine dose; a second dose was given at week 3. Serum samples were obtained at baseline and at each weekly follow-up, and antibodies were tested at 1-2 weeks after the first vaccine dose, at week 3 with the administration of the second vaccine dose, and at weeks 4-5 (ie, 1-2 weeks after the second vaccine dose). Participants with comorbidities were approached to participate in an enriched comorbidities subgroup, and at least two neutralising assays were done during the 5 weeks of follow-up in those individuals. IgG assays were done for the entire study population, whereas IgM, IgA, and neutralising antibody assays were done only in the enriched comorbidities subgroup. Concentrations of IgG greater than 0·62 sample-to-cutoff (s/co) ratio and of IgA greater than 1·1 s/co, and titres of neutralising antibodies greater than 10 were considered positive. Scatter plot and correlation analyses, logistic and linear regression analyses, and linear mixed models were used to investigate the longitudinal antibody responses. FINDINGS: Between Dec 19, 2020, and Jan 30, 2021, we obtained 4026 serum samples from 2607 eligible, vaccinated participants. 342 individuals were included in the enriched comorbidities subgroup. The first vaccine dose elicited positive IgG and neutralising antibody responses at week 3 in 707 (88·0%) of 803 individuals, and 264 (71·0%) of 372 individuals, respectively, which were rapidly increased at week 4 (ie, 1 week after the second vaccine dose) in 1011 (98·4%) of 1027 and 357 (96·5%) of 370 individuals, respectively. Over 4 weeks of follow-up after vaccination, a high correlation (r=0·92) was detected between IgG against the receptor-binding domain and neutralising antibody titres. First-dose induced IgG response was significantly lower in individuals aged 66 years and older (ratio of means 0·25, 95% CI 0·19-0·31) and immunosuppressed individuals (0·21, 0·14-0·31) compared with individuals aged 18·00-45·99 years and individuals with no immunosuppression, respectively. This disparity was partly abrogated following the second dose. Overall, endpoint regression analysis showed that lower antibody concentrations were consistently associated with male sex (ratio of means 0·84, 95% CI 0·80-0·89), older age (ie, ≥66 years; 0·64, 0·58-0·71), immunosuppression (0·44, 0·33-0·58), and other specific comorbidities: diabetes (0·88, 0·79-0·98), hypertension (0·90, 0·82-0·98), heart disease (0·86, 0·75-1·00), and autoimmune diseases (0·82, 0·73-0·92). INTERPRETATION: BNT162b2 vaccine induces a robust and rapid antibody response. The significant correlation between receptor-binding domain IgG antibodies and neutralisation titres suggests that IgG antibodies might serve as a correlate of neutralisation. The second vaccine dose is particularly important for older and immunosuppressed individuals, highlighting the need for timely second vaccinations and potentially a revaluation of the long gap between doses in some countries. Antibody responses were reduced in susceptible populations and therefore they might be more prone to breakthrough infections. FUNDING: Sheba Medical Center, Israel Ministry of Health.

DNA Repair Biomarker for Lung Cancer Risk and its Correlation With Airway Cells Gene Expression.

BACKGROUND: Improving lung cancer risk assessment is required because current early-detection screening criteria miss most cases. We therefore examined the utility for lung cancer risk assessment of a DNA Repair score obtained from OGG1, MPG, and APE1 blood tests. In addition, we examined the relationship between the level of DNA repair and global gene expression. METHODS: We conducted a blinded case-control study with 150 non-small cell lung cancer case patients and 143 control individuals. DNA Repair activity was measured in peripheral blood mononuclear cells, and the transcriptome of nasal and bronchial cells was determined by RNA sequencing. A combined DNA Repair score was formed using logistic regression, and its correlation with disease was assessed using cross-validation; correlation of expression to DNA Repair was analyzed using Gene Ontology enrichment. RESULTS: DNA Repair score was lower in case patients than in control individuals, regardless of the case's disease stage. Individuals at the lowest tertile of DNA Repair score had an increased risk of lung cancer compared to individuals at the highest tertile, with an odds ratio (OR) of 7.2 (95% confidence interval [CI] = 3.0 to 17.5; P < .001), and independent of smoking. Receiver operating characteristic analysis yielded an area under the curve of 0.89 (95% CI = 0.82 to 0.93). Remarkably, low DNA Repair score correlated with a broad upregulation of gene expression of immune pathways in patients but not in control individuals. CONCLUSIONS: The DNA Repair score, previously shown to be a lung cancer risk factor in the Israeli population, was validated in this independent study as a mechanism-based cancer risk biomarker and can substantially improve current lung cancer risk prediction, assisting prevention and early detection by computed tomography scanning.

Outbreaks of Kingella kingae Infections in Daycare Centers Suggest Tissue Tropism of the Causative Strains.

BACKGROUND: Although Kingella kingae is recognized as an important pediatric pathogen, our knowledge of the virulence factors involved in the invasion of specific host's tissues is limited. Outbreaks of K kingae infections in daycare centers represent natural experiments in which a single virulent strain, introduced into a cohort of susceptible young children, causes multiple infections. If K kingae strains exhibit tissue tropism, the syndromes observed in a given cluster of cases would be relatively homogeneous. METHODS: Clinical data of all the K kingae outbreaks known to date were gathered and analyzed. The clinical syndromes diagnosed in the affected attendees were classified as septic arthritis, osteomyelitis, tenosynovitis, soft tissue infection, bacteremia with no focal disease, endocarditis, and meningitis, and computed separately. To assess the similarity of the clinical syndromes detected within outbreaks, we used the Cramer V statistic, which is a measure of the association between 2 nominal variables and, for the purposes of the study, between the detected clinical syndromes and the outbreaks. RESULTS: A total of 23 outbreaks involving 61 attendees were identified. The mean±SD attack rate in the affected classrooms was 15.8% ± 4.8%, and the K kingae colonization rate among the attendees was 54.8% ± 25.3%. Seventy-two separate foci of infection were diagnosed. Osteomyelitis and septic arthritis were the most common clinical syndromes and were diagnosed in 26 children each, followed by tenosynovitis in 4 children. The clinical syndromes diagnosed among attendees to the same classroom showed a statistically significant tendency to be similar (P = .015). CONCLUSIONS: The distribution of clinical syndromes in clusters of K kingae infections differs from that of sporadic cases. The causative strains combine enhanced virulence and high transmissibility, and show tropism toward bones, joints, and tendon sheaths. This information can be used to identify virulence factors associated with invasion of these specific host tissues.

Spatial heterogeneity stabilizes predator-prey interactions at the microscale while patch connectivity controls their outcome.

Natural landscapes are both fragmented and heterogeneous, affecting the distribution of organisms, and their interactions. While predation in homogeneous environments increases the probability of population extinction, fragmentation/heterogeneity promotes coexistence and enhances community stability as shown by experimentation with animals and microorganisms, and supported by theory. Patch connectivity can modulate such effects but how microbial predatory interactions are affected by water-driven connectivity is unknown. In soil, patch habitability by microorganisms, and their connectivity depend upon the water saturation degree (SD). Here, using the obligate bacterial predator Bdellovibrio bacteriovorus, and a Burkholderia prey, we show that soil spatial heterogeneity profoundly affects predatory dynamics, enhancing long-term co-existence of predator and prey in a SD-threshold dependent-manner. However, as patches and connectors cannot be distinguished in these soil matrices, metapopulations cannot be invoked to explain the dynamics of increased persistence. Using a set of experiments combined with statistical and physical models we demonstrate and quantify how under full connectivity, predation is independent of water content but depends on soil microstructure characteristics. In contrast, the SD below which predation is largely impaired corresponds to a threshold below which the water network collapses and water connectivity breaks down, preventing the bacteria to move within the soil matrix.

Update of a Meta-analysis of Sensory Symptoms in ASD: A New Decade of Research.

This meta-analysis updated evidence regarding sensory over-responsivity (SOR), under-responsivity (SUR) and seeking symptoms in individuals with autism spectrum disorders (ASDs) relative to typical controls and those with other conditions. Fifty-five questionnaire studies included 4606 individuals with ASD. Moderators tested were age, IQ, male ratio, matching group, and self-report. Compared to typical controls, effect size was large and significant for SOR, SUR, and Seeking but heterogeneous. For Seeking, age, IQ and self-report were significant moderators. Compared with developmental disorders (DDs) groups, effect size was significantly positive for SOR and Seeking; whereas compared with other clinical groups, only SOR was significant. These findings highlight the core nature of sensory symptoms in ASD and particularly SOR. Explanatory factors are yet to be revealed.

Traffic-related Air Pollution and Pregnancy Loss.

BACKGROUND: Traffic-related air pollution has been linked to multiple adverse pregnancy outcomes. However, few studies have examined pregnancy loss, targeting losses identified by hospital records, a large limitation as it does not capture events not reported to the medical system. METHODS: We used a novel variation of the time-series design to determine the association, and identify the critical window of vulnerability, between week-to-week traffic-related air pollution and conceptions resulting in live births, using nitrogen dioxide (NO2) as a traffic emissions tracer. We used information from all live births recorded at Beth Israel Deaconess Medical Center in Boston, MA (2000-2013) and all live births in Tel Aviv District, Israel (2010-2013). RESULTS: In Boston (68,969 live births), the strongest association was during the 15th week of gestation; for every 10 ppb of NO2 increase during that week, we observed a lower rate of live births (rate ratio [RR] = 0.87; 95% confidence interval [CI], 0.78, 0.97), using live birth-identified conceptions to infer pregnancy losses. In the Tel Aviv District (95,053 live births), the strongest estimate was during the 16th gestational week gestation (RR = 0.82; 95% CI, 0.76, 0.90 per 10 ppb of NO2). CONCLUSIONS: Using weekly conceptions ending in live birth rather than identified pregnancy losses, we comprehensively analyzed the relationship between air pollution and all pregnancy loss throughout gestation. The observed results, with remarkable similarity in two independent locations, suggest that higher traffic-related air pollution levels are associated with pregnancy loss, with strongest estimates between the 10th and 20th gestational weeks.

Correction of sampling bias in a cross-sectional study of post-surgical complications.

Cross-sectional designs are often used to monitor the proportion of infections and other post-surgical complications acquired in hospitals. However, conventional methods for estimating incidence proportions when applied to cross-sectional data may provide estimators that are highly biased, as cross-sectional designs tend to include a high proportion of patients with prolonged hospitalization. One common solution is to use sampling weights in the analysis, which adjust for the sampling bias inherent in a cross-sectional design. The current paper describes in detail a method to build weights for a national survey of post-surgical complications conducted in Israel. We use the weights to estimate the probability of surgical site infections following colon resection, and validate the results of the weighted analysis by comparing them with those obtained from a parallel study with a historically prospective design.

Transmission of Staphylococcus aureus from mothers to newborns.

BACKGROUND: The study objective was to define the risk factors and the route of Staphylococcus aureus transmission between mother and newborn. METHODS: Women at late pregnancy were screened for nasal and vaginal S. aureus colonization. Newborns were screened for nasal, auricular, umbilical, and rectal colonization at birth and before discharge. Carrier mothers and their newborns were rescreened at 1 month. Pulse-field gel electrophoresis was used to assess strain genetic relatedness. RESULTS: Of the 208 women screened, 34% were colonized with S. aureus. Overall, by 72-100 hours after birth, the cumulative incidence of S. aureus acquisition was 42.6/100 newborns of carrier mothers versus 7.4/100 newborns of noncarrier mothers (adjusted risk ratio = 5.7; 95% confidence interval [CI], 2.3-13.9). The risk to acquire a maternal strain was significantly higher than nonmaternal strain (adjusted risk ratio = 1.5; 95% CI, 1.3-1.9); Newborns to carrier mothers were also at a risk to acquire nonmaternal S. aureus strains compared with newborns to noncarrier mothers (adjusted risk ratio = 2.9; 95% CI, 1.6-5.4). The cumulative incidence of S. aureus acquisition was similar among newborns delivered by cesarean versus vaginal delivery (24.5 vs. 23.0/100 cases). At 1-month follow-up, the cumulative incidence of S. aureus acquisition reached 69.7/100 newborns of carrier mothers.Genetically identical strains were isolated in 32/40 (80%) mother-newborn pairs, among these, the source of the newborn strain was a maternal nasal strain in 29/32 (90%). CONCLUSIONS: Newborns of carrier mothers are at risk to acquire S. aureus colonization. Most newborns of carrier mothers are colonized within the first month of life. Horizontal transmission from the mother is probably the major source for S. aureus carriage in newborns.

Estimation of the ROC curve under verification bias.

The ROC (receiver operating characteristic) curve is the most commonly used statistical tool for describing the discriminatory accuracy of a diagnostic test. Classical estimation of the ROC curve relies on data from a simple random sample from the target population. In practice, estimation is often complicated due to not all subjects undergoing a definitive assessment of disease status (verification). Estimation of the ROC curve based on data only from subjects with verified disease status may be badly biased. In this work we investigate the properties of the doubly robust (DR) method for estimating the ROC curve under verification bias originally developed by Rotnitzky, Faraggi and Schisterman (2006) for estimating the area under the ROC curve. The DR method can be applied for continuous scaled tests and allows for a non-ignorable process of selection to verification. We develop the estimator's asymptotic distribution and examine its finite sample properties via a simulation study. We exemplify the DR procedure for estimation of ROC curves with data collected on patients undergoing electron beam computer tomography, a diagnostic test for calcification of the arteries.