Mitochondrial DNA (mtDNA) analysis has proved useful in studies of recent human evolution and the genetic affinities of human groups of different geographical regions. As part of an extensive survey ...of mtDNA diversity in present-day Pacific populations, we obtained sequence information of the hypervariable mtDNA control region of 452 individuals from various localities in the western Pacific. The mtDNA types fell into three major groups which reflect the settlement history of the area. Interestingly, we detected an extremely rare point mutation at high frequency in the small island of Nguna in the Melanesian archipelago of Vanuatu. Phylogenetic analysis of the mtDNA data indicated that the mutation was present in individuals of separate mtDNA lineages. We propose that the multiple occurrence of a rare mutation event in one isolated locality is highly improbable, and that recombination between different mtDNA types is a more likely explanation for our observation. If correct, this conclusion has important implications for the use of mtDNA in phylogenetic and evolutionary studies.
Calcite-rich soils (calcrete) in alluvium and colluvium at Solitario Wash, Crater Flat, Nevada, USA, contain pedogenic calcite and opaline silica similar to soils present elsewhere in the semi-arid ...southwestern United States. Nevertheless, a ground-water discharge origin for the Solitario Wash soil deposits was proposed in a series of publications proposing elevation-dependent variations of carbon and oxygen isotopes in calcrete samples. Discharge of ground water in the past would raise the possibility of future flooding in the unsaturated zone at Yucca Mountain, Nevada, site of a proposed high-level nuclear waste repository. New geochemical and carbon, oxygen, strontium, and uranium-series isotopic data disprove the presence of systematic elevation-isotopic composition relations, which are the main justification given for a proposed ground-water discharge origin of the calcrete deposits at Solitario Wash. Values of δ¹³C (-4.1 to -7.8 per mil per thousand), δ¹⁸O (23.8-17.2per thousand), ⁸⁷Sr/⁸⁶Sr (0.71270-0.71146), and initial ²³⁴U/²³⁸U activity ratios of about 1.6 in the new calcrete samples are within ranges previously observed in pedogenic carbonate deposits at Yucca Mountain and are incompatible with a ground-water origin for the calcrete. Variations in carbon and oxygen isotopes in Solitario Wash calcrete likely are caused by pedogenic deposition from meteoric water under varying Quaternary climatic conditions over hundreds of thousands of years.
The optimal fractionation schedule of post lumpectomy radiation therapy remains controversial. The objective of this study was to describe the fractionation of post-lumpectomy radiation therapy (RT) ...in Ontario, before and after the seminal Ontario Clinical Oncology Group (OCOG) trial, which showed the equivalence of 16- and 25-fraction schedules.
This was a retrospective cohort study conducted by linking electronic treatment records to a population-based cancer registry. The study population included all patients who underwent lumpectomy for invasive breast cancer in Ontario, Canada, between 1984 and 2008.
Over the study period, 41,747 breast cancer patients received post lumpectomy radiation therapy to the breast only. Both 16- and 25-fraction schedules were commonly used throughout the study period. In the early 1980s, shorter fractionation schedules were used in >80% of cases. Between 1985 and 1995, the proportion of patients treated with shorter fractionation decreased to 48%. After completion of the OCOG trial, shorter fractionation schemes were once again widely adopted across Ontario, and are currently used in about 71% of cases; however, large intercenter variations in fractionation persisted.
The use of shorter schedules of post lumpectomy RT in Ontario increased after completion of the OCOG trial, but the trial had a less normative effect on practice than expected.
To examine the association of COVID-19 convalescent plasma transfusion with mortality and the differences between subgroups in hospitalized patients with COVID-19.
On October 26, 2022, a systematic ...search was performed for clinical studies of COVID-19 convalescent plasma in the literature from January 1, 2020, to October 26, 2022. Randomized clinical trials and matched cohort studies investigating COVID-19 convalescent plasma transfusion compared with standard of care treatment or placebo among hospitalized patients with confirmed COVID-19 were included. The electronic search yielded 3841 unique records, of which 744 were considered for full-text screening. The selection process was performed independently by a panel of 5 reviewers. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data were extracted by 5 independent reviewers in duplicate and pooled using an inverse-variance random effects model. The prespecified end point was all-cause mortality during hospitalization.
Thirty-nine randomized clinical trials enrolling 21,529 participants and 70 matched cohort studies enrolling 50,160 participants were included in the systematic review. Separate meta-analyses reported that transfusion of COVID-19 convalescent plasma was associated with a decrease in mortality compared with the control cohort for both randomized clinical trials (odds ratio OR, 0.87; 95% CI, 0.76-1.00) and matched cohort studies (OR, 0.76; 95% CI, 0.66-0.88). The meta-analysis of subgroups revealed 2 important findings. First, treatment with convalescent plasma containing high antibody levels was associated with a decrease in mortality compared with convalescent plasma containing low antibody levels (OR, 0.85; 95% CI, 0.73 to 0.99). Second, earlier treatment with COVID-19 convalescent plasma was associated with a decrease in mortality compared with the later treatment cohort (OR, 0.63; 95% CI, 0.48 to 0.82).
During COVID-19 convalescent plasma use was associated with a 13% reduced risk of mortality, implying a mortality benefit for hospitalized patients with COVID-19, particularly those treated with convalescent plasma containing high antibody levels treated earlier in the disease course.
Neutrophil (PMN) transepithelial migration is dependent on the leukocyte beta(2) integrin CD11b/CD18, yet the identity of epithelial counterreceptors remain elusive. Recently, a JAM protein family ...member termed JAM-C was implicated in leukocyte adhesive interactions; however, its expression in epithelia and role in PMN-epithelial interactions are unknown. Here, we demonstrate that JAM-C is abundantly expressed basolaterally in intestinal epithelia and localizes to desmosomes but not tight junctions. Desmosomal localization of JAM-C was further confirmed by experiments aimed at selective disruption of tight junctions and desmosomes. In assays of PMN transepithelial migration, both JAM-C mAbs and JAM-C/Fc chimeras significantly inhibited the rate of PMN transmigration. Additional experiments revealed specific binding of JAM-C to CD11b/CD18 and provided evidence of other epithelial ligands for CD11b/CD18. These findings represent the first demonstration of direct adhesive interactions between PMN and epithelial intercellular junctions (desmosomes) that regulate PMN transepithelial migration and also suggest that JAM-C may play a role in desmosomal structure/function.
Internationally, guidelines to prevent secondary transmission of Shigella infection vary widely. Cases, their contacts with diarrhoea, and those in certain occupational groups are frequently excluded ...from work, school, or daycare. In the Netherlands, all contacts attending pre-school (age 0-3) and junior classes in primary school (age 4-5), irrespective of symptoms, are also excluded pending microbiological clearance. We identified risk factors for secondary Shigella infection (SSI) within households and evaluated infection control policy in this regard. This retrospective cohort study of households where a laboratory confirmed Shigella case was reported in Amsterdam (2002-2009) included all households at high risk for SSI (i.e. any household member under 16 years). Cases were classified as primary, co-primary or SSIs. Using univariable and multivariable binomial regression with clustered robust standard errors to account for household clustering, we examined case and contact factors (Shigella serotype, ethnicity, age, sex, household size, symptoms) associated with SSI in contacts within households. SSI occurred in 25/ 337 contacts (7.4%): 20% were asymptomatic, 68% were female, and median age was 14 years (IQR: 4-38). In a multivariable model adjusted for case and household factors, only diarrhoea in contacts was associated with SSI (IRR 8.0, 95% CI:2.7-23.8). In a second model, factors predictive of SSI in contacts were the age of case (0-3 years (IRR.sub.casegreater than or equai to6 years:2.5, 95% CI:1.1-5.5) and 4-5 years (IRR.sub.casegreater than or equai to6 years:2.2, 95% CI:1.1-4.3)) and household size (>6 persons (IRR.sub.2-4 persons 3.4, 95% CI:1.2-9.5)). To identify symptomatic and asymptomatic SSI, faecal screening should be targeted at all household contacts of preschool cases (0-3 years) and cases attending junior class in primary school (4-5 years) and any household contact with diarrhoea. If screening was limited to these groups, only one asymptomatic adult carrier would have been missed, and potential exclusion of 70 asymptomatic contacts 6 years old from school or daycare, who were contacts of cases of all ages, could have been avoided.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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