Bonobos Maintain Immune System Diversity with Three Functional Types of MHC-B

Fast-evolving MHC class I polymorphism serves to diversify NK cell and CD8 T cell responses in individuals, families, and populations. Because only chimpanzee and bonobo have strict orthologs of all HLA class I, their study gives unique perspectives on the human condition. We defined polymorphism of Papa-B, the bonobo ortholog of HLA-B, for six wild bonobo populations. Sequences for Papa-B exon 2 and 3 were determined from the genomic DNA in 255 fecal samples, minimally representing 110 individuals. Twenty-two Papa-B alleles were defined, each encoding a different Papa-B protein. No Papa-B is identical to any chimpanzee Patr-B, human HLA-B, or gorilla Gogo-B. Phylogenetic analysis identified a Glade of MHC-B, defined by residues 45-74 of the alpha(1) domain, which is broadly conserved among bonobo, chimpanzee, and gorilla. Bonobo populations have 3-14 Papa-B allotypes. Three Papa-B are in all populations, and they are each of a different functional type: allotypes having the Bw4 epitope recognized by killer cell Ig-like receptors of NK cells, allotypes having the Cl epitope also recognized by killer cell Ig-like receptors, and allotypes having neither epitope. For population Malebo, these three Papa-B are the only Papa-B allotypes. Although small in number, their sequence divergence is such that the nucleotide diversity (mean proportional distance) of Papa-B in Malebo is greater than in the other populations and is also greater than expected for random combinations of three Papa-B. Overall, Papa-B has substantially less diversity than Patr-B in chimpanzee subspecies and HLA-B in indigenous human populations, consistent with bonobo having experienced narrower population bottlenecks

Thermal ablation versus cryotherapy or loop excision to treat women positive for cervical precancer on visual inspection with acetic acid test: pilot phase of a randomised controlled trial

Background: Cryotherapy is standard practice for treating patients with cervical precancer in see-and-treat programmes in low-income and middle-income countries (LMICs). Because of logistical difficulties with cryotherapy (eg, the necessity, costs, and supply chain difficulties of refrigerant gas; equipment failure; and treatment duration >10 min), a battery-operated thermal ablator that is lightweight and portable has been developed. We aimed to compare thermal ablation using the new device with cryotherapy. Methods: We report the pilot phase of a randomised controlled trial in routine screen-and-treat clinics providing cervical screening using visual inspection with acetic acid (VIA) in Lusaka, Zambia. We recruited non-pregnant women, aged 25 years or older, who were eligible for ablative therapy. We randomly assigned participants (1:1:1) to thermal ablation, cryotherapy, or large loop excision of the transformation zone (LLETZ), using computer-generated allocation. The randomisation was concealed but the nurses providing treatment and the participants were unmasked. Thermal ablation was achieved using the Liger thermal ablator (using 1–5 overlapping applications of the probe heated to 100°C, each application lasting for 40 s), cryotherapy was carried out using the double-freeze technique (freeze for 3 min, thaw for 5 min, and freeze again for 3 min), and LLETZ (using a large loop driven by an electro-surgical unit to excise the transformation zone) was done under local anaesthesia. The primary endpoint was treatment success, defined as either human papillomavirus (HPV) type-specific clearance among participants who were positive for the same HPV type at baseline, or a negative VIA test at 6-month follow-up, if the baseline HPV test was negative. Per protocol analyses were done. Enrolment for the full trial is ongoing. Here, we present findings from a prespecified pilot phase of the full trial. The final analysis of the full trial will assess non-inferiority of the groups for the primary efficacy endpoint. The study is registered with ClinicalTrials.gov, number NCT02956239. Findings: Between Aug 2, 2017, and Jan 15, 2019, 750 participants were randomly assigned (250 per group). 206 (84%) participants in the cryotherapy group, 197 (81%) in the thermal ablation group, and 204 (84%) in the LLETZ group attended the 6-month follow-up examination. Treatment success was reported in 120 (60%) of 200 participants in the cryotherapy group, 123 (64%) of 192 in the thermal ablation group, and 134 (67%) of 199 in the LLETZ group (p=0·31). Few participants complained of moderate to severe pain in any group immediately after the procedure (six [2%] of 250 in the cryotherapy group, four [2%] of 250 in the thermal ablation group, and five [2%] of 250 in the LLETZ group) and 2 weeks after the procedure (one [<1%] of 241 in the cryotherapy group, none of 242 in the thermal ablation group, and two [<1%] of 237 in the LLETZ group). None of the participants reported any complication requiring medical consultation or admission to hospital. Interpretation: Results from this pilot study preliminarily suggest that thermal ablation has similar treatment success to cryotherapy, without the practical disadvantages of providing cryotherapy in an LMIC. However, the study was not powered to establish the similarity between the techniques, and results from the ongoing randomised controlled trial are need to confirm these results. Funding: US National Institutes of Health

Gynaecological morbidity among HIV positive pregnant women in Cameroon

<p>Abstract</p> <p>Objective</p> <p>To compare the prevalence of gynaecological conditions among HIV infected and non-infected pregnant women.</p> <p>Methods</p> <p>Two thousand and eight (2008) pregnant women were screened for HIV, lower genital tract infections and lower genital tract neoplasia at booking antenatal visit.</p> <p>Results</p> <p>About 10% (198/2008) were HIV positive. All lower genital tract infections except candidiasis were more prevalent among HIV positive compared to HIV negative women: vaginal candidiasis (36.9% vs 35.4%; <it>p </it>= 0.678), Trichomoniasis (21.2% vs 10.6%; <it>p </it>< 0.001), gonorrhoea (10.1% vs 2.5%; <it>p </it>< 0.001), bacterial vaginosis (21.2% vs 15.2%; <it>p </it>= 0.026), syphilis (35.9% vs 10.6%; <it>p </it>< 0.001), and <it>Chlamydia trachomatis </it>(38.4% vs 7.1%; <it>p </it>< 0.001). Similarly, HIV positive women more likely to have preinvasive cervical lesions: low-grade squamous intraepithelial lesion (SIL) (18.2% vs 4.4%; <it>p </it>< 0.001) and high-grade squamous intraepithelial lesion (12.1% vs 1.5%; <it>p </it>< 0.001).</p> <p>Conclusion</p> <p>We conclude that (i) sexually transmitted infections (STIs) are common in both HIV positive and HIV negative pregnant women in Cameroon, and (ii) STIs and preinvasive cervical lesions are more prevalent in HIV-infected pregnant women compared to their non-infected compatriots. We recommend routine screening and treatment of STIs during antenatal care in Cameroon and other countries with similar social profiles.</p

Statistical analysis of the velocity field in a mechanical precessing jet flow

An experimental investigation of a precessing jet issuing from a mechanically rotating nozzle directed at an angle of α=45° relative to the axis of rotation is reported. Both conventional and conditional statistics of the velocity field of the jet were measured using a combined hot-wire and cold-wire (to identify any reverse flow) probe. Three distinct values (≈0.005, 0.01, and 0.02) of the precession Strouhal number Stp (≡ rotation frequency × nozzle diameter / jet exit bulk velocity) were used to assess the effect of varying Stp. The measurements reveal that the Strouhal number in general has significant influence on the entire mixing field generated by a precessing jet. The occurrence of precession at all the Strouhal numbers of investigation produces a central recirculation zone at x ≤ 7d, where x is a distance measured from the rotating nozzle exit. A critical Strouhal number, i.e., Stp,cr ≈0.008 for the present case, is identified: at Stp ≥ Stp,cr the core jet converges to the axis of rotation while at Stp ≥ Stp,cr it does not. The characteristics of the turbulent flow in the near and intermediate regions are quite different and depend upon the magnitude of Stp. The near-field region, x/d ≤ 10-15, is dominated by a regime of global precession of the entire jet. As a result, the large-scale entrainment of the ambient fluid is substantially enhanced while the fine-scale turbulent mixing is suppressed. Under the supercritical regime (i.e., Stp ≥ Stp,cr), the jet in the far field resembles some features of the nonprecessing counterpart. Nevertheless, significant differences still retain in the statistical properties. © 2005 American Institute of Physics.J. Mi and G. J. Natha

A genome-wide association study suggests that a locus within the ataxin 2 binding protein 1 gene is associated with hand osteoarthritis: the Treat-OA consortium

To identify the susceptibility gene in hand osteoarthritis (OA) the authors used a two-stage approach genome-wide association study using two discovery samples (the TwinsUK cohort and the Rotterdam discovery subset; a total of 1804 subjects) and four replication samples (the Chingford Study, the Chuvasha Skeletal Aging Study, the Rotterdam replication subset and the Genetics, Arthrosis, and Progression (GARP) Study; a total of 3266 people). Five single-nucleotide polymorphisms (SNPs) had a likelihood of association with hand OA in the discovery stage and one of them (rs716508), was successfully confirmed in the replication stage (meta-analysis p = 1.81×10−5). The C allele conferred a reduced risk of 33% to 41% using a case–control definition. The SNP is located in intron 1 of the A2BP1 gene. This study also found that the same allele of the SNP significantly reduced bone density at both the hip and spine (p<0.01), suggesting the potential mechanism of the gene in hand OA might be via effects on subchondral bone. The authors' findings provide a potential new insight into genetic mechanisms in the development of hand OA

Classification and incidence of cancers in adolescents and young adults in England 1979–1997

Cancer patients aged 15–24 years have distinct special needs. High quality cancer statistics are required for service planning. Data presented by primary site are inappropriate for this age group. We have developed a morphology-based classification and applied it to national cancer registration data for England 1979–1997. The study included 25 000 cancers and 134 million person–years at risk. Rates for each diagnostic group by age, sex and time period (1979–83, 1984–87, 1988–92, 1993–1997) were calculated. Overall rates in 15–19 and 20–24-year-olds were 144 and 226 per million person–years respectively. Lymphomas showed the highest rates in both age groups. Rates for leukaemias and bone tumours were lower in 20–24 year olds. Higher rates for carcinomas, central nervous system tumours, germ-cell tumours, soft tissue sarcomas and melanoma were seen in the older group. Poisson regression showed incidence increased over the study period by an average of 1.5% per annum (P<0.0001). Significant increases were seen in non-Hodgkins lymphoma (2.3%), astrocytoma (2.3%), germ-cell tumours (2.3%), melanoma (5.1%) and carcinoma of the thyroid (3.5%) and ovary (3.0%). Cancers common in the elderly are uncommon in adolescents and young adults. The incidence of certain cancers in the latter is increasing. Future studies should be directed towards aetiology

Multidimensional Model of Racial Identity: A Reconceptualization of African American Racial Identity

Research on African American racial identity has utilized 2 distinct approaches. The mainstream approach has focused on universal properties associated with ethnic and racial identities. In contrast, the underground approach has focused on documenting the qualitative meaning of being African American, with an emphasis on the unique cultural and historical experiences of African Americans. The Multidimensional Model of Racial Identity (MMRI) represents a synthesis of the strengths of these two approaches. The underlying assumptions associated with the model are explored. The model proposes 4 dimensions of African American racial identity: salience, centrality, regard, and ideology. A description of these dimensions is provided along with a discussion of how they interact to influence behavior at the level of the event. We argue that the MMRI has the potential to make contributions to traditional research objectives of both approaches, as well as to provide the impetus to explore new questions.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68695/2/10.1207_s15327957pspr0201_2.pd

The mosaic of KIR haplotypes in rhesus macaques

To further refine and improve biomedical research in rhesus macaques, it is necessary to increase our knowledge concerning both the degree of allelic variation (polymorphism) and diversity (gene copy number variation) in the killer cell immunoglobulin-like receptor (KIR) gene cluster. Pedigreed animals in particular should be studied, as segregation data will provide clues to the linkage of particular KIR genes/alleles segregating on a haplotype and to its gene content as well. A dual strategy allowed us to screen the presence and absence of genes and the corresponding transcripts, as well as to track differences in transcription levels. On the basis of this approach, 14 diverse KIR haplotypes have been described. These haplotypes consist of multiple inhibitory and activating Mamu-KIR genes, and any gene present on one haplotype may be absent on another. This suggests that the cost of accelerated evolution by recombination may be the loss of certain framework genes on a haplotype