Protection and Waning of Natural and Hybrid Immunity to SARS-CoV-2.

BACKGROUND: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) provides natural immunity against reinfection. Recent studies have shown waning of the immunity provided by the BNT162b2 vaccine. The time course of natural and hybrid immunity is unknown. METHODS: Using the Israeli Ministry of Health database, we extracted data for August and September 2021, when the B.1.617.2 (delta) variant was predominant, on all persons who had been previously infected with SARS-CoV-2 or who had received coronavirus 2019 vaccine. We used Poisson regression with adjustment for confounding factors to compare the rates of infection as a function of time since the last immunity-conferring event. RESULTS: The number of cases of SARS-CoV-2 infection per 100,000 person-days at risk (adjusted rate) increased with the time that had elapsed since vaccination with BNT162b2 or since previous infection. Among unvaccinated persons who had recovered from infection, this rate increased from 10.5 among those who had been infected 4 to less than 6 months previously to 30.2 among those who had been infected 1 year or more previously. Among persons who had received a single dose of vaccine after previous infection, the adjusted rate was low (3.7) among those who had been vaccinated less than 2 months previously but increased to 11.6 among those who had been vaccinated at least 6 months previously. Among previously uninfected persons who had received two doses of vaccine, the adjusted rate increased from 21.1 among those who had been vaccinated less than 2 months previously to 88.9 among those who had been vaccinated at least 6 months previously. CONCLUSIONS: Among persons who had been previously infected with SARS-CoV-2 (regardless of whether they had received any dose of vaccine or whether they had received one dose before or after infection), protection against reinfection decreased as the time increased since the last immunity-conferring event; however, this protection was higher than that conferred after the same time had elapsed since receipt of a second dose of vaccine among previously uninfected persons. A single dose of vaccine after infection reinforced protection against reinfection.

Protection by a Fourth Dose of BNT162b2 against Omicron in Israel.

BACKGROUND: On January 2, 2022, Israel began administering a fourth dose of BNT162b2 vaccine to persons 60 years of age or older. Data are needed regarding the effect of the fourth dose on rates of confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and of severe coronavirus disease 2019 (Covid-19). METHODS: Using the Israeli Ministry of Health database, we extracted data on 1,252,331 persons who were 60 years of age or older and eligible for the fourth dose during a period in which the B.1.1.529 (omicron) variant of SARS-CoV-2 was predominant (January 10 through March 2, 2022). We estimated the rate of confirmed infection and severe Covid-19 as a function of time starting at 8 days after receipt of a fourth dose (four-dose groups) as compared with that among persons who had received only three doses (three-dose group) and among persons who had received a fourth dose 3 to 7 days earlier (internal control group). For the estimation of rates, we used quasi-Poisson regression with adjustment for age, sex, demographic group, and calendar day. RESULTS: The number of cases of severe Covid-19 per 100,000 person-days (unadjusted rate) was 1.5 in the aggregated four-dose groups, 3.9 in the three-dose group, and 4.2 in the internal control group. In the quasi-Poisson analysis, the adjusted rate of severe Covid-19 in the fourth week after receipt of the fourth dose was lower than that in the three-dose group by a factor of 3.5 (95% confidence interval [CI], 2.7 to 4.6) and was lower than that in the internal control group by a factor of 2.3 (95% CI, 1.7 to 3.3). Protection against severe illness did not wane during the 6 weeks after receipt of the fourth dose. The number of cases of confirmed infection per 100,000 person-days (unadjusted rate) was 177 in the aggregated four-dose groups, 361 in the three-dose group, and 388 in the internal control group. In the quasi-Poisson analysis, the adjusted rate of confirmed infection in the fourth week after receipt of the fourth dose was lower than that in the three-dose group by a factor of 2.0 (95% CI, 1.9 to 2.1) and was lower than that in the internal control group by a factor of 1.8 (95% CI, 1.7 to 1.9). However, this protection waned in later weeks. CONCLUSIONS: Rates of confirmed SARS-CoV-2 infection and severe Covid-19 were lower after a fourth dose of BNT162b2 vaccine than after only three doses. Protection against confirmed infection appeared short-lived, whereas protection against severe illness did not wane during the study period.

Assessing the roles of nitrogen, biomass, and niche dimensionality as drivers of species loss in grassland communities.

Eutrophication is a major driver of species loss in plant communities worldwide. However, the underlying mechanisms of this phenomenon are controversial. Previous studies have raised three main explanations: 1) High levels of soil resources increase standing biomass, thereby intensifying competitive interactions (the "biomass-driven competition hypothesis"). 2) High levels of soil resources reduce the potential for resource-based niche partitioning (the "niche dimension hypothesis"). 3) Increasing soil nitrogen causes stress by changing the abiotic or biotic conditions (the "nitrogen detriment hypothesis"). Despite several syntheses of resource addition experiments, so far, no study has tested all of the hypotheses together. This is a major shortcoming, since the mechanisms underlying the three hypotheses are not independent. Here, we conduct a simultaneous test of the three hypotheses by integrating data from 630 resource addition experiments located in 99 sites worldwide. Our results provide strong support for the nitrogen detriment hypothesis, weaker support for the biomass-driven competition hypothesis, and negligible support for the niche dimension hypothesis. The results further show that the indirect effect of nitrogen through its effect on biomass is minor compared to its direct effect and is much larger than that of all other resources (phosphorus, potassium, and water). Thus, we conclude that nitrogen-specific mechanisms are more important than biomass or niche dimensionality as drivers of species loss under high levels of soil resources. This conclusion is highly relevant for future attempts to reduce biodiversity loss caused by global eutrophication.

Waning Immunity after the BNT162b2 Vaccine in Israel.

BACKGROUND: In December 2020, Israel began a mass vaccination campaign against coronavirus disease 2019 (Covid-19) by administering the BNT162b2 vaccine, which led to a sharp curtailing of the outbreak. After a period with almost no cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, a resurgent Covid-19 outbreak began in mid-June 2021. Possible reasons for the resurgence were reduced vaccine effectiveness against the delta (B.1.617.2) variant and waning immunity. The extent of waning immunity of the vaccine against the delta variant in Israel is unclear. METHODS: We used data on confirmed infection and severe disease collected from an Israeli national database for the period of July 11 to 31, 2021, for all Israeli residents who had been fully vaccinated before June 2021. We used a Poisson regression model to compare rates of confirmed SARS-CoV-2 infection and severe Covid-19 among persons vaccinated during different time periods, with stratification according to age group and with adjustment for possible confounding factors. RESULTS: Among persons 60 years of age or older, the rate of infection in the July 11-31 period was higher among persons who became fully vaccinated in January 2021 (when they were first eligible) than among those fully vaccinated 2 months later, in March (rate ratio, 1.6; 95% confidence interval [CI], 1.3 to 2.0). Among persons 40 to 59 years of age, the rate ratio for infection among those fully vaccinated in February (when they were first eligible), as compared with 2 months later, in April, was 1.7 (95% CI, 1.4 to 2.1). Among persons 16 to 39 years of age, the rate ratio for infection among those fully vaccinated in March (when they were first eligible), as compared with 2 months later, in May, was 1.6 (95% CI, 1.3 to 2.0). The rate ratio for severe disease among persons fully vaccinated in the month when they were first eligible, as compared with those fully vaccinated in March, was 1.8 (95% CI, 1.1 to 2.9) among persons 60 years of age or older and 2.2 (95% CI, 0.6 to 7.7) among those 40 to 59 years of age; owing to small numbers, the rate ratio could not be calculated among persons 16 to 39 years of age. CONCLUSIONS: These findings indicate that immunity against the delta variant of SARS-CoV-2 waned in all age groups a few months after receipt of the second dose of vaccine.

Protection against Covid-19 by BNT162b2 Booster across Age Groups.

BACKGROUND: After promising initial results from the administration of a third (booster) dose of the BNT162b2 messenger RNA vaccine (Pfizer-BioNTech) to persons 60 years of age or older, the booster campaign in Israel was gradually expanded to persons in younger age groups who had received a second dose at least 5 months earlier. METHODS: We extracted data for the period from July 30 to October 10, 2021, from the Israel Ministry of Health database regarding 4,696,865 persons 16 years of age or older who had received two doses of BNT162b2 at least 5 months earlier. In the primary analysis, we compared the rates of confirmed coronavirus disease 2019 (Covid-19), severe illness, and death among those who had received a booster dose at least 12 days earlier (booster group) with the rates among those who had not received a booster (nonbooster group). In a secondary analysis, we compared the rates in the booster group with the rates among those who had received a booster 3 to 7 days earlier (early postbooster group). We used Poisson regression models to estimate rate ratios after adjusting for possible confounding factors. RESULTS: The rate of confirmed infection was lower in the booster group than in the nonbooster group by a factor of approximately 10 (range across five age groups, 9.0 to 17.2) and was lower in the booster group than in the early postbooster group by a factor of 4.9 to 10.8. The adjusted rate difference ranged from 57.0 to 89.5 infections per 100,000 person-days in the primary analysis and from 34.4 to 38.3 in the secondary analysis. The rates of severe illness in the primary and secondary analyses were lower in the booster group by a factor of 17.9 (95% confidence interval [CI], 15.1 to 21.2) and 6.5 (95% CI, 5.1 to 8.2), respectively, among those 60 years of age or older and by a factor of 21.7 (95% CI, 10.6 to 44.2) and 3.7 (95% CI, 1.3 to 10.2) among those 40 to 59 years of age. The adjusted rate difference in the primary and secondary analyses was 5.4 and 1.9 cases of severe illness per 100,000 person-days among those 60 years of age or older and 0.6 and 0.1 among those 40 to 59 years of age. Among those 60 years of age or older, mortality was lower by a factor of 14.7 (95% CI, 10.0 to 21.4) in the primary analysis and 4.9 (95% CI, 3.1 to 7.9) in the secondary analysis. The adjusted rate difference in the primary and secondary analyses was 2.1 and 0.8 deaths per 100,000 person-days. CONCLUSIONS: Across the age groups studied, rates of confirmed Covid-19 and severe illness were substantially lower among participants who received a booster dose of the BNT162b2 vaccine than among those who did not.

Protection of BNT162b2 Vaccine Booster against Covid-19 in Israel.

BACKGROUND: On July 30, 2021, the administration of a third (booster) dose of the BNT162b2 messenger RNA vaccine (Pfizer-BioNTech) was approved in Israel for persons who were 60 years of age or older and who had received a second dose of vaccine at least 5 months earlier. Data are needed regarding the effect of the booster dose on the rate of confirmed coronavirus 2019 disease (Covid-19) and the rate of severe illness. METHODS: We extracted data for the period from July 30 through August 31, 2021, from the Israeli Ministry of Health database regarding 1,137,804 persons who were 60 years of age or older and had been fully vaccinated (i.e., had received two doses of BNT162b2) at least 5 months earlier. In the primary analysis, we compared the rate of confirmed Covid-19 and the rate of severe illness between those who had received a booster injection at least 12 days earlier (booster group) and those who had not received a booster injection (nonbooster group). In a secondary analysis, we evaluated the rate of infection 4 to 6 days after the booster dose as compared with the rate at least 12 days after the booster. In all the analyses, we used Poisson regression after adjusting for possible confounding factors. RESULTS: At least 12 days after the booster dose, the rate of confirmed infection was lower in the booster group than in the nonbooster group by a factor of 11.3 (95% confidence interval [CI], 10.4 to 12.3); the rate of severe illness was lower by a factor of 19.5 (95% CI, 12.9 to 29.5). In a secondary analysis, the rate of confirmed infection at least 12 days after vaccination was lower than the rate after 4 to 6 days by a factor of 5.4 (95% CI, 4.8 to 6.1). CONCLUSIONS: In this study involving participants who were 60 years of age or older and had received two doses of the BNT162b2 vaccine at least 5 months earlier, we found that the rates of confirmed Covid-19 and severe illness were substantially lower among those who received a booster (third) dose of the BNT162b2 vaccine.

Early, continuing exposure to cow's milk formula and cow's milk allergy: The COMEET study, a single center, prospective interventional study.

BACKGROUND: Cow's milk allergy (CMA) is a common food allergy among infants. Information regarding the best timing for first exposure to cow's milk formula (CMF) is controversial and more evidence is required. Few randomized control trials have tried to accurately assess the timing and preventive effect of exposure to CMF on small cohorts. OBJECTIVE: This study assessed the association between early, continuing exposure to CMF on the basis of the parents' preferences and the development of immunoglobulin E (IgE)-mediated CMA in a large birth cohort. METHODS: Newborns were prospectively recruited shortly before birth and divided into 2 groups according to parental feeding preference for the first 2 months of life: (1) exclusive breastfeeding (EBF); or (2) at least 1 meal of CMF (with or without breastfeeding) daily. Infants were followed up monthly until the age of 12 months. RESULTS: Among 1992 infants participating in the study, 1073 (53.86%) were in the EBF group until 2 months of age. IgE-mediated CMA was confirmed in 0.85% (n = 17); all were in the EBF group. Within this group, the prevalence of IgE-mediated CMA was 1.58% compared with 0 in the other groups (relative risk, 29.98; P < .001). Post hoc analysis revealed IgE-mediated CMA prevalence of 0.7% in the per-protocol EBF group vs 3.27% among breastfed infants who were exposed to a small amount of CMF during the first 2 months of life. A family atopic background did not affect the results. CONCLUSION: Early, continuing exposure to CMF from birth has the potential to prevent the development of IgE-mediated CMA and should be encouraged. However, the exposure needs to be consistent because occasional exposure increases the risk of developing IgE-mediated CMA and should be avoided.

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.

Pfizer-BioNTech vaccine effectiveness against Sars-Cov-2 infection: Findings from a large observational study in Israel.

Development of an effective vaccine against Covid-19 is crucial to reducing infection. mRNA BNT162b2, developed and manufactured by Pfizer-BioNTech, was one of the first FDA-approved vaccinations reporting high efficacy (95%) and minimal side effects. Evaluating effectiveness of BNT162b2 in a general population has been made possible after the implementation of a nation-wide vaccination program in Israel. This retrospective cohort study was carried out in Maccabi HealthCare services, Israel among 1.6 million members aged 16 and over. The population was divided into those who were at least seven days post- second vaccination and those who had not been vaccinated. Number of days till the end of the study or Covid-19 infection, Covid-19-related hospitalization and mortality was calculated for each participant between 18.1.2021 to 25.4.2021. Participants who had reached day eight after second vaccination during the study period could contribute days to both groups. Vaccine efficacy (VE) was calculated using a conditional Poisson model, controlling for age group, gender, hypertension, diabetes and obesity, fitted within clusters defined by geographical statistical area and calendar week. BNT162b2 was found effective for the total population group for infection, hospitalization and mortality, with adjusted VE of 93·0% (CI:92·6-93·4%), 93·4% (CI:91·9-94·7%) and 91·1% (CI:86·5-94·1%) respectively. VE for infection was lower for participants aged 75 and over, and for those with hypertension, diabetes and obesity. This study strengthens the evidence that the Pfizer-BioNTech vaccination is effective in preventing infection, hospitalization and mortality.

Inverse probability weighting methods for Cox regression with right-truncated data.

Right-truncated data arise when observations are ascertained retrospectively, and only subjects who experience the event of interest by the time of sampling are selected. Such a selection scheme, without adjustment, leads to biased estimation of covariate effects in the Cox proportional hazards model. The existing methods for fitting the Cox model to right-truncated data, which are based on the maximization of the likelihood or solving estimating equations with respect to both the baseline hazard function and the covariate effects, are numerically challenging. We consider two alternative simple methods based on inverse probability weighting (IPW) estimating equations, which allow consistent estimation of covariate effects under a positivity assumption and avoid estimation of baseline hazards. We discuss problems of identifiability and consistency that arise when positivity does not hold and show that although the partial tests for null effects based on these IPW methods can be used in some settings even in the absence of positivity, they are not valid in general. We propose adjusted estimating equations that incorporate the probability of observation when it is known from external sources, which results in consistent estimation. We compare the methods in simulations and apply them to the analyses of human immunodeficiency virus latency.

Nonparametric estimation of transition probabilities for a general progressive multi-state model under cross-sectional sampling.

Nonparametric estimation of the transition probability matrix of a progressive multi-state model is considered under cross-sectional sampling. Two different estimators adapted to possibly right-censored and left-truncated data are proposed. The estimators require full retrospective information before the truncation time, which, when exploited, increases efficiency. They are obtained as differences between two survival functions constructed for sub-samples of subjects occupying specific states at a certain time point. Both estimators correct the oversampling of relatively large survival times by using the left-truncation times associated with the cross-sectional observation. Asymptotic results are established, and finite sample performance is investigated through simulations. One of the proposed estimators performs better when there is no censoring, while the second one is strongly recommended with censored data. The new estimators are applied to data on patients in intensive care units (ICUs).

Inverse probability weighted Cox regression for doubly truncated data.

Doubly truncated data arise when event times are observed only if they fall within subject-specific, possibly random, intervals. While non-parametric methods for survivor function estimation using doubly truncated data have been intensively studied, only a few methods for fitting regression models have been suggested, and only for a limited number of covariates. In this article, we present a method to fit the Cox regression model to doubly truncated data with multiple discrete and continuous covariates, and describe how to implement it using existing software. The approach is used to study the association between candidate single nucleotide polymorphisms and age of onset of Parkinson's disease.

[FETAL WEIGHT CHARTS IN THE ISRAELI POPULATION].

BACKGROUND: Sonographic estimated fetal weight is performed by measuring the fetal organs' biometry and introducing the data into a formula. The calculated value is then compared with reference charts and serves as a critical component in pregnancy follow-up. Ideally the charts should be appropriate to the specific population. OBJECTIVES: To display and validate sonographic based Israeli-matched, intrauterine fetal weight curves. METHODS: The international Hadlock and Souka formulas, were chosen and assessed using over 70,000 ultrasound examinations from Israel. Since the Souka formula is appropriate only after 30 weeks of pregnancy, we used Hadlock's formula for pregnancies under 30 weeks and the comparison between the Hadlock and Souka formulas was made thereafter. In order to evaluate the Israeli population charts, 6389 pregnant women were examined sonographically in the last three days of pregnancy, and the estimated fetal weights were compared with the actual newborn weights. RESULTS: Fetal weight charts were constructed. Both equations were efficient, but the combination of Hadlock formula until 30 weeks and Souka between 31 to 42 weeks tended to be more accurate. CONCLUSIONS: We described fetal weight charts based on common equations, using biometric measurements derived from the Israeli population. We recommend the charts presented here as the universal reference for all the professionals involved in perinatal care in Israel. DISCUSSION: Fetal growth abnormalities are determined by the curve chosen. Birthweight curves may underdiagnose restrictions in fetal growth because of the disorders associated with preterm delivery. Sonographic biometric curves represent physiological growth more reliably.

Nonparametric estimation in the illness-death model using prevalent data.

We study nonparametric estimation of the illness-death model using left-truncated and right-censored data. The general aim is to estimate the multivariate distribution of a progressive multi-state process. Maximum likelihood estimation under censoring suffers from problems of uniqueness and consistency, so instead we review and extend methods that are based on inverse probability weighting. For univariate left-truncated and right-censored data, nonparametric maximum likelihood estimation can be considerably improved when exploiting knowledge on the truncation distribution. We aim to examine the gain in using such knowledge for inverse probability weighting estimators in the illness-death framework. Additionally, we compare the weights that use truncation variables with the weights that integrate them out, showing, by simulation, that the latter performs more stably and efficiently. We apply the methods to intensive care units data collected in a cross-sectional design, and discuss how the estimators can be easily modified to more general multi-state models.

Recognizing the problem of delayed entry in time-to-event studies: Better late than never for clinical neuroscientists.

EDITOR'S NOTE: One of the greatest differences I encountered in moving from being Editor-in-Chief of a basic science journal to the same position at Annals of Neurology was the much greater importance of meticulous review of the statistical treatment of data. In basic science, the conditions of an experiment can be set up by the investigator so that relatively simple statistical treatments can often be used with clear-cut results. Comparing the treatment and outcomes of human studies is much messier. Humans have a history before the study started; they have lives that often cause them to deviate from the protocol; and it is much harder to measure the outcomes because our methods have to be so much less invasive than they can be in animal studies. In addition, unlike mice or rats, which are deliberately inbred in a laboratory to minimize variation between animals, we are a wild species with enormous genetic and environmental variability. We solved the problem of the lack of statistical sophistication of the scientific editors by bringing in an expert in study design and statistical analysis, Dr Rebecca Betensky, a Professor of Biostatistics at the Harvard T. H. Chan School of Public Health, who serves as our Statistical Editor. We have weekly editorial conferences where the Associate Editors, Rebecca, and I consider which of the papers that were reviewed in the previous week should be published. Each week, it seems, we are treated to a private tutorial (sometimes more than one) on the complexities of study design and statistical analysis in the papers we are considering. I have learned a great deal at these meetings and thought that this education should be extended to our readers, and so I have prevailed upon Dr Betensky to address some recurring topics in our editorial conferences. We begin this month with the concept of delayed entry, a common problem in human studies that many investigators and reviewers fail to take into account. We have decided to publish this series under the NeuroGenesis section of the Annals, because this section is devoted to the career development of neurologists, and it seems critical to the professional judgment of every academic neurologist to assimilate the concepts in this series, both to improve our own work and to evaluate the work of other neurologists more critically. -C.B.S.

Comparing estimation approaches for the illness-death model under left truncation and right censoring.

Left-truncated data arise when lifetimes are observed only if they are larger than independent truncation times. For example, in a cross-sectional sampling, only individuals who live long enough to be present on the sampling day are observed. There are several ways to perform statistical inference under this setting. One can do the following: (i) use an unconditional approach, (ii) condition on the value of the truncation variable, or (iii) condition on all the history up to the time of truncation. The latter two approaches are equivalent when analyzing univariate survival outcomes but differ under the multi-state framework. In this paper, we consider the illness-death model and compare between the three estimation approaches in a parametric regression framework. We show that approach (ii) is more efficient than the standard approach (iii), although it requires more computational effort. Approach (i) is the most efficient approach, but it requires knowledge on the distribution of the truncation variable and hence is less robust. The methods are compared using a theoretical example and simulations and are applied to intensive care units data collected in a cross-sectional design, where the illness state corresponds to a bloodstream infection.

A comparison of methods for construction of fetal reference charts.

Reference charts for fetal measures are used for early detection of pregnancies that should be monitored closely. Construction of reference charts corresponds to estimation of quantiles of a distribution as a function of gestational age. Existing methods have been developed under various modeling assumptions, typically by fitting a polynomial regression to certain functionals of the distributions (e.g., mean, standard deviation, and quantiles). We use a large dataset to compare various existing methods for construction of reference charts. We also relax the assumptions of a parametric polynomial link between the distribution parameters and age and consider cubic splines and discretization of age in order to compare charts based on more flexible and simpler models, respectively. We compare the different methods using various tools and demonstrate the importance of considering performance measures calculated from age-stratified data. We also examine the question of sample size. We compare our charts to similar charts that have been recently published and emphasize that the source of an apparent heterogeneity should be investigated. We conclude that the choice of which method to use for construction of reference charts should take the following into account: available sample size, validity of normality assumption, and results of various performance measures.

Fetal Biometry in the Israeli Population: New Reference Charts.

BACKGROUND: Selection of appropriate reference charts for fetal biometry is mandatory to ensure an accurate diagnosis. Most hospitals and clinics in Israel use growth curves from the United States. Charts developed in different populations do not perform well in the Israeli population. OBJECTIVES: To construct new reference charts for fetal biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC) and femur length (FL), using a large sample of fetuses examined at 14-42 weeks gestational age in a medical center and a community ultrasound unit located in two different regions of Israel. METHODS: Data from the medical center and the community clinic were pooled. The mean and standard error of each measure for each week was calculated. Based on these, reference charts were calculated using quantiles of the normal distribution. The performance of the reference charts was assessed by comparing the new values to empiric quantiles. RESULTS: Biometric measurements were obtained for 79,328 fetuses. Growth charts were established based on these measurements. The overall performance of the curves was very good, with only a few exceptions among the higher quantiles in the third trimester in the medical center subsample. CONCLUSIONS: We present new local reference charts for fetal biometry, derived from a large and minimally selected Israeli population. We suggest using these new charts in routine daily obstetric practice.

Analyzing multiple cross-sectional samples with application to hospitalization time after surgeries.

Repeated cross-sectional sampling results in multiple biased samples with possibly different weight functions. The standard non-parametric maximum likelihood estimator for the lifetime distribution of interest solves a set of nonlinear equations, and its variance has a very complicated form. We suggest a simple closed-form estimator for the case where entrances to the population of interest follow a Poisson model. The variance of the estimator and confidence intervals are easily calculated. Our motivating example concerns a series of cross-sectional surveys conducted in Israeli hospitals. We discuss the bias mechanism in our data and suggest a simple design plan that provides valid estimators even when the weight functions are unknown. The new method is applied to estimate the distribution of hospitalization time after bowel and hernia surgeries.

Competitive exclusion, beta diversity, and deterministic vs. stochastic drivers of community assembly.

Species diversity has two components - number of species and spatial turnover in species composition (beta-diversity). Using a field experiment focusing on a system of Mediterranean grasslands, we show that interspecific competition may influence the two components in the same direction or in opposite directions, depending on whether competitive exclusions are deterministic or stochastic. Deterministic exclusions reduce both patch-scale richness and beta-diversity, thereby homogenising the community. Stochastic extinctions reduce richness at the patch scale, but increase the differences in species composition among patches. These results indicate that studies of competitive effects on beta diversity may help to distinguish between deterministic and stochastic components of competitive exclusion. Such distinction is crucial for understanding the causal relationship between competition and species diversity, one of the oldest and most fundamental questions in ecology.