Mortality in a Migrating Mennonite Church Congregation

Preston\u27s two-census method of demographic estimation is applied to three pairs of reconstructed censuses from the records of a migrating Mennonite church congregation covering the period 1780-1890, The three pairs of censuses correspond to three periods (1780-1790, 1850-1860, and 1880-1890) and to stays in three settings (Prussia, Russia, and Kansas, respectively). The Mennonites\u27 stay in Prussia was a period of hardship. In Russia they expanded their economic base and developed new farming methods, dramatically increasing their productivity. The Mennonites took these skills to Kansas, where they continued to be successful. The increase in life expectancy at age 5 corroborates this picture. The Prussian period exhibits the shortest life expectancy for both sexes. After the move to Russia, life expectancy increased for both sexes and continued to increase with the move to Kansas. The model also provides limited evidence for fertility depression following the move to Kansas

Changes in Completed Family Size and Reproductive Span in Anabaptist Populations

The Anabaptist Amish, Hutterite and Mennonite peoples trace their origins to the Reformation. Although they share certain beliefs, such as adult baptism and the separation of church and state, each group is culturally unique. The Hutterite and Amish are highly fertile and their populations exhibit stable rates of growth. These demographic characteristics reflect communal living among the Hutterites and labor intensive farming practices among the Amish. The Mennonites are the most receptive Anabaptist group to outside socioeconomic influences and provide a demographic contrast to the more conservative Amish and Hutterites. Demographic data collected during a study of aging in Mennonite population samples from Goessel and Meridian, Kansas, 1980, and Henderson, Nebraska, 1981, formed the basis of a cohort analysis in order to assess fertility change over time. Completed family size has decreased significantly in all three communities since 1870. Since the early 1900\u27s the mean age of the mother at first birth has fluctuated but the mean age of mother at the birth of the last child is decreasing significantly for the communities of Goessel and Henderson, thus effectively shortening the reproductive span. The pattern is somewhat different for Meridian, the most conservative of the three communities

Immunoglobulin Haplotypes – Markers of Reproductive Success

Immunoglobulin haplotypes are highly polymorphic and are useful for analyses of both macro- and microdifferentiation of populations. The origins of this diversity are not known, but recent reports suggest strong selection at this locus. Increased rates of first-trimester spontaneous abortions have been reported when parents share GM phenotypes. Reduced fertility has been observed in mixed European descent white and Hutterite populations when both parents share immunoglobulin haplotypes. Population samples with completed family information and GM haplotype data are rare; the objective here is to provide this information on another sample. A sample of 242 Mennonite couples with mothers older than 40 years was divided into 3 groups of matings based on how many haplotypes were shared: 0, 1, or 2. The distribution of mean completed family sizes for the three groups were 3.35 ± 1.85 ( n = 23), 3.47 ± 1.69 ( n = 128), and 3.37 ± 1.60 ( n = 91), respectively; these values were not significantly different (F = 0.145, p = 0.865). The log-rank test was used to compare the time-to-next-birth curves. The intervals between first and later births (2-4 births) were not significantly different for the three subgroups either. There is also only limited evidence for segregation distortion in another sample of 923 offspring (in which at least one parent is heterozygous)

Reproductive Measures, Fitness, and Migrating Mennonites: An Evolutionary Analysis

Given the same reproductive span, more children with shorter interbirth intervals and less parental attention per child should not do as well. There should be intermediate optima in family sizes. but only two studies have demonstrated optima. The goal here is to determine whether the relationship between fitness and fertility is linear and whether this relationship masks underlying variation in reproductive behaviors in a Mennonite congregation that lived in two disease settings. Prussia/Russia Vs. Kansas. The relationships between children born and fitness were determined by calculating linear and quadratic regressions for total. Prussia/Russia vs. Kansas. and families with deaths vs. families with no deaths for total. Prussia/Russia. and Kansas. Variation was examined in terms of measures of reproductive success and reproductive span. Comparisons were made by t tests with Bonferroni correction. Regressions demonstrate equally well that the more children women bear, the higher the reproductive success. whether in the harsher disease ecology of rural Prussia/Russia or in less challenging rural Kansas and whether the women experience deaths or not. Prussian/Russian mothers bore significantly more children (6.5 +/- 0.3) than Kansan mothers (5.6 divided by- 0.2) over longer reproductive spans but did not significantly increase the number of surviving children (4.9 +/- 0.2 vs. 4.7 +/- 0.2, respectively). Families experiencing deaths vs. no deaths exhibit significantly longer reproductive spans. reflecting a significantly earlier start at childbearing and a later finish, and produce significantly more children (5.4 +/- 0.2 vs. 4.2 divided by- 0.2). Cox regressions were run. and the most significant covariates to negatively affect survivorship to 15 years were death in the family and length of the previous interbirth intervals. There was variation in families. but perhaps most had adequate nutrition, which may explain the lack of optima in fitness

Immunoglobulin Haplotype Frequencies in Anabaptist Population Samples: Kansas and Nebraska Mennonites and Indiana Amish

Anabaptist history is a chronicle of repeated migrations, fissions, and fusions of various subgroups. The effects of these events should be evident in the population biology of the Anabaptist groups. No prior genetic studies have included the polymorphic and highly informative immunoglobulin markers. Here, 685 serum samples representing 1 Amish and 3 Mennonite community samples (7 congregations) were studied for immunoglobulin allotypes. The haplotypes IGHG*F B, IGHG*A,Z G, and IGHG*A,X,Z G range in frequency from 0.542 to 0.765, 0.123 to 0.290, and 0.075 to 0.170, respectively. IGK*1 frequencies range from 0.035 to 0.077, All frequencies are within expected ranges for central and western European population samples, There was considerable intergroup variability among the Anabaptist samples that was statistically significant x29 = 22.63, 0.005 \u3c p \u3c 0.01), Principal component analyses, including the immunoglobulin allotype frequencies and published data on ABO, MN, and Rhesus (Dd) markers, demonstrate that the Mennonite congregation samples with close historical ties group together acid are distinct from the Amish and Meridian congregation samples

Retreatment for hepatitis C virus direct-acting antiviral therapy virological failure in primary and tertiary settings: The REACH-C cohort

Virological failure occurs in a small proportion of people treated for hepatitis C virus (HCV) with direct-acting antiviral (DAA) therapies. This study assessed retreatment for virological failure in a large real-world cohort. REACH-C is an Australian observational study (n = 10,843) evaluating treatment outcomes of sequential DAA initiations across 33 health services between March 2016 to June 2019. Virological failure retreatment data were collected until October 2020. Of 408 people with virological failure (81% male; median age 53; 38% cirrhosis; 56% genotype 3), 213 (54%) were retreated once; 15 were retreated twice. A range of genotype specific and pangenotypic DAAs were used to retreat virological failure in primary (n = 56) and tertiary (n = 157) settings. Following sofosbuvir/velpatasvir/voxilaprevir availability in 2019, the proportion retreated in primary care increased from 21% to 40% and median time to retreatment initiation declined from 294 to 152 days. Per protocol (PP) sustained virological response (SVR12) was similar for people retreated in primary and tertiary settings (80% vs 81%; p = 1.000). In regression analysis, sofosbuvir/velpatasvir/voxilaprevir (vs. other regimens) significantly decreased likelihood of second virological failure (PP SVR12 88% vs. 77%; adjusted odds ratio [AOR] 0.29; 95%CI 0.11–0.81); cirrhosis increased likelihood (PP SVR12 69% vs. 91%; AOR 4.26; 95%CI 1.64–11.09). Indigenous Australians had lower likelihood of retreatment initiation (AOR 0.36; 95%CI 0.15–0.81). Treatment setting and prescriber type were not associated with retreatment initiation or outcome. Virological failure can be effectively retreated in primary care. Expanded access to simplified retreatment regimens through decentralized models may increase retreatment uptake and reduce HCV-related mortality

Investigation of hospital discharge cases and SARS-CoV-2 introduction into Lothian care homes

Background The first epidemic wave of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Scotland resulted in high case numbers and mortality in care homes. In Lothian, over one-third of care homes reported an outbreak, while there was limited testing of hospital patients discharged to care homes. Aim To investigate patients discharged from hospitals as a source of SARS-CoV-2 introduction into care homes during the first epidemic wave. Methods A clinical review was performed for all patients discharges from hospitals to care homes from 1st March 2020 to 31st May 2020. Episodes were ruled out based on coronavirus disease 2019 (COVID-19) test history, clinical assessment at discharge, whole-genome sequencing (WGS) data and an infectious period of 14 days. Clinical samples were processed for WGS, and consensus genomes generated were used for analysis using Cluster Investigation and Virus Epidemiological Tool software. Patient timelines were obtained using electronic hospital records. Findings In total, 787 patients discharged from hospitals to care homes were identified. Of these, 776 (99%) were ruled out for subsequent introduction of SARS-CoV-2 into care homes. However, for 10 episodes, the results were inconclusive as there was low genomic diversity in consensus genomes or no sequencing data were available. Only one discharge episode had a genomic, time and location link to positive cases during hospital admission, leading to 10 positive cases in their care home. Conclusion The majority of patients discharged from hospitals were ruled out for introduction of SARS-CoV-2 into care homes, highlighting the importance of screening all new admissions when faced with a novel emerging virus and no available vaccine

SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway

Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant

Ledipasvir and Sofosbuvir Plus Ribavirin for Treatment of HCV Infection in Patients With Advanced Liver Disease

There are no effective and safe treatments for chronic hepatitis C virus (HCV) infection of patients who have advanced liver disease. In this phase 2, open-label study, we assessed treatment with the NS5A inhibitor ledipasvir, the nucleotide polymerase inhibitor sofosbuvir, and ribavirin in patients infected with HCV genotypes 1 or 4. Cohort A enrolled patients with cirrhosis and moderate or severe hepatic impairment who had not undergone liver transplantation. Cohort B enrolled patients who had undergone liver transplantation: those without cirrhosis; those with cirrhosis and mild, moderate, or severe hepatic impairment; and those with fibrosing cholestatic hepatitis. Patients were assigned randomly (1:1) to receive 12 or 24 weeks of a fixed-dose combination tablet containing ledipasvir and sofosbuvir, once daily, plus ribavirin. The primary end point was sustained virologic response at 12 weeks after the end of treatment (SVR12). We enrolled 337 patients, 332 (99%) with HCV genotype 1 infection and 5 (1%) with HCV genotype 4 infection. In cohort A (nontransplant), SVR12 was achieved by 86%–89% of patients. In cohort B (transplant recipients), SVR12 was achieved by 96%–98% of patients without cirrhosis or with compensated cirrhosis, by 85%−88% of patients with moderate hepatic impairment, by 60%–75% of patients with severe hepatic impairment, and by all 6 patients with fibrosing cholestatic hepatitis. Response rates in the 12- and 24-week groups were similar. Thirteen patients (4%) discontinued the ledipasvir and sofosbuvir combination prematurely because of adverse events; 10 patients died, mainly from complications related to hepatic decompensation. The combination of ledipasvir, sofosbuvir, and ribavirin for 12 weeks produced high rates of SVR12 in patients with advanced liver disease, including those with decompensated cirrhosis before and after liver transplantation. ClinTrials.gov: NCT01938430