Deep sequencing of the vaginal microbiota of women with HIV

Background:Women living with HIV and co-infected with bacterial vaginosis (BV) are at higher risk for transmitting HIV to a partner or newborn. It is poorly understood which bacterial communities constitute BV or the normal vaginal microbiota among this population and how the microbiota associated with BV responds to antibiotic treatment. Methods and Findings: The vaginal microbiota of 132 HIV positive Tanzanian women, including 39 who received metronidazole treatment for BV, were profiled using Illumina to sequence the V6 region of the 16S rRNA gene. Of note, Gardnerella vaginalis and Lactobacillus iners were detected in each sample constituting core members of the vaginal microbiota. Eight major clusters were detected with relatively uniform microbiota compositions. Two clusters dominated by L. iners or L. crispatus were strongly associated with a normal microbiota. The L. crispatus dominated microbiota were associated with low pH, but when L. crispatus was not present, a large fraction of L. iners was required to predict a low pH. Four clusters were strongly associated with BV, and were dominated by Prevotella bivia, Lachnospiraceae, or a mixture of different species. Metronidazole treatment reduced the microbial diversity and perturbed the BV-associated microbiota, but rarely resulted in the establishment of a lactobacilli-dominated microbiota. Conclusions: Illumina based microbial profiling enabled high though-put analyses of microbial samples at a high phylogenetic resolution. The vaginal microbiota among women living with HIV in Sub-Saharan Africa constitutes several profiles associated with a normal microbiota or BV. Recurrence of BV frequently constitutes a different BV-associated profile than before antibiotic treatment

Utilisation of specialist epilepsy services and antiseizure medication adherence rates in a cohort of people with epilepsy (PWE) accessing emergency care

Background: An epilepsy-related attendance at A&E is associated an increased risk of subsequent death within 6 months. Although further work is required to provide a definitive explanation to account for these findings, in the interim it would seem reasonable that services are designed to ensure timely access and provide support at a time of greatest risk. We aim to determine the frequency of patients accessing specialist neurology services following an epilepsy-related admission/unscheduled care episode and consider ASM adherence at the point of attendance. Methods: Patients were identified retrospectively via the NHS Greater Glasgow and Clyde live integrated epilepsy Dashboard following an unscheduled epilepsy-related admission or A&E attendance between 1st January 2022 and 30th June 2022. We calculated adherence to anti-seizure medication for a period of 6 months prior to admission and defined poor medication adherence as a medication possession ratio of less than 80%. We evaluated the rate of any outpatient neurology clinic attendance in the subsequent 3, 6 and 12 months following an epilepsy-related unscheduled care episode. Additional clinical information was identified via the electronic patient records. Results: Between 1st Jan 2022 and 30th June 2022, there were 266 emergency care seizure-related attendances. The mean age at attendance was 46 years (range: 16-91). Most of PWE were males (63%) and 37% were females. Epilepsy classification-29.3% had GGE, 41.7 % had focal epilepsy, and in 29% of cases the epilepsy was unclassified. Of the admissions, 107/ 266 (40.2%) generated follow-up within 6 months of attendance. Poor medication adherence was noted in 54/266 (20.3%). 28.2% of cases had input from on-call neurology service during admission/ED attendance, and of those 60% had ASM adjusted. 18% of attendances had a background diagnosis of learning disability. One-third of attendances of PWE had a history of mental health disorder 35% (93/266). 25% of ED attendances noted an active history of alcohol consumption misuse or/and recreational drug use. 14 (5.5%) of PWE died during the period of interest (12 months following the last ED visit). In 6/14 (42.3%) death was associated with poor medication adherence. Conclusion: This study demonstrates that a significant proportion of patients who experienced seizure-related admissions/ attendance did not access specialist neurology services in a timely manner. In addition, poor medication adherence remains a problem for a substantial number of people living with epilepsy. Early access to specialist services may go some way to improving care and reducing excessive mortality in PWE by allowing anti-seizure medication to be titrated and poor medication adherence to be addressed in those at greatest risk

Study of the B^0 Semileptonic Decay Spectrum at the Upsilon(4S) Resonance

We have made a first measurement of the lepton momentum spectrum in a sample of events enriched in neutral B's through a partial reconstruction of B0 --> D*- l+ nu. This spectrum, measured with 2.38 fb**-1 of data collected at the Upsilon(4S) resonance by the CLEO II detector, is compared directly to the inclusive lepton spectrum from all Upsilon(4S) events in the same data set. These two spectra are consistent with having the same shape above 1.5 GeV/c. From the two spectra and two other CLEO measurements, we obtain the B0 and B+ semileptonic branching fractions, b0 and b+, their ratio, and the production ratio f+-/f00 of B+ and B0 pairs at the Upsilon(4S). We report b+/b0=0.950 (+0.117-0.080) +- 0.091, b0 = (10.78 +- 0.60 +- 0.69)%, and b+ = (10.25 +- 0.57 +- 0.65)%. b+/b0 is equivalent to the ratio of charged to neutral B lifetimes, tau+/tau0.Comment: 14 page, postscript file also available at http://w4.lns.cornell.edu/public/CLN

Radiative Decay Modes of the D0D^{0} Meson

Using data recorded by the CLEO-II detector at CESR we have searched for four radiative decay modes of the $D^0$ meson: $D^0\to\phi\gamma$, $D^0\to\omega\gamma$, $D^0\to\bar{K}^{*}\gamma$, and $D^0\to\rho^0\gamma$. We obtain 90% CL upper limits on the branching ratios of these modes of $1.9\times 10^{-4}$, $2.4\times 10^{-4}$, $7.6\times 10^{-4}$ and $2.4\times 10^{-4}$ respectively.Comment: 15 page postscript file, postscript file also available through http://w4.lns.cornell.edu/public/CLN

Measurement of the Mass Splittings between the bbˉχb,J(1P)b\bar{b}\chi_{b,J}(1P) States

We present new measurements of photon energies and branching fractions for the radiative transitions: Upsilon(2S)->gamma+chi_b(J=0,1,2). The masses of the chi_b states are determined from the measured radiative photon energies. The ratio of mass splittings between the chi_b substates, r==(M[J=2]-M[J=1])/(M[J=1]-M[J=0]) with M the chi_b mass, provides information on the nature of the bbbar confining potential. We find r(1P)=0.54+/-0.02+/-0.02. This value is in conflict with the previous world average, but more consistent with the theoretical expectation that r(1P)<r(2P); i.e., that this mass splittings ratio is smaller for the chi_b(1P) triplet than for the chi_b(2P) triplet.Comment: 11 page postscript file, postscript file also available through http://w4.lns.cornell.edu/public/CLN

Frequency of LATE neuropathologic change across the spectrum of Alzheimer’s disease neuropathology: combined data from 13 community-based or population-based autopsy cohorts

Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) and Alzheimer’s disease neuropathologic change (ADNC) are each associated with substantial cognitive impairment in aging populations. However, the prevalence of LATE-NC across the full range of ADNC remains uncertain. To address this knowledge gap, neuropathologic, genetic, and clinical data were compiled from 13 high-quality community- and population-based longitudinal studies. Participants were recruited from United States (8 cohorts, including one focusing on Japanese–American men), United Kingdom (2 cohorts), Brazil, Austria, and Finland. The total number of participants included was 6196, and the average age of death was 88.1 years. Not all data were available on each individual and there were differences between the cohorts in study designs and the amount of missing data. Among those with known cognitive status before death (n = 5665), 43.0% were cognitively normal, 14.9% had MCI, and 42.4% had dementia—broadly consistent with epidemiologic data in this age group. Approximately 99% of participants (n = 6125) had available CERAD neuritic amyloid plaque score data. In this subsample, 39.4% had autopsy-confirmed LATE-NC of any stage. Among brains with “frequent” neuritic amyloid plaques, 54.9% had comorbid LATE-NC, whereas in brains with no detected neuritic amyloid plaques, 27.0% had LATE-NC. Data on LATE-NC stages were available for 3803 participants, of which 25% had LATE-NC stage > 1 (associated with cognitive impairment). In the subset of individuals with Thal Aβ phase = 0 (lacking detectable Aβ plaques), the brains with LATE-NC had relatively more severe primary age-related tauopathy (PART). A total of 3267 participants had available clinical data relevant to frontotemporal dementia (FTD), and none were given the clinical diagnosis of definite FTD nor the pathological diagnosis of frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP). In the 10 cohorts with detailed neurocognitive assessments proximal to death, cognition tended to be worse with LATE-NC across the full spectrum of ADNC severity. This study provided a credible estimate of the current prevalence of LATE-NC in advanced age. LATE-NC was seen in almost 40% of participants and often, but not always, coexisted with Alzheimer’s disease neuropathology

Studies of the Cabbibo-Suppressed Decays D+→π0ℓ+νD^+ \to \pi^0 \ell^+ \nu and D+→ηe+νeD^+ \to \eta e^+ \nu_e

Using 4.8 fb$^{-1}$ of data taken with the CLEO II detector, the branching fraction for the Cabibbo-suppressed decay $D^+\to\pi^0\ell^+\nu$ measured relative to the Cabibbo favored decay $D^+\to\bar{K^0}\ell^+\nu$ is found to be $0.046\pm 0.014\pm 0.017$. Using $V_{cs}$ and $V_{cd}$ from unitarity constraints, we determine $| f_+^{\pi}(0)/f_+^K(0)|^2=0.9\pm 0.3\pm 0.3$ We also present a 90% confidence level upper limit for the branching ratio of the decay $D^+ \to \eta e^+\nu_e$ relative to that for $D^+ \to \pi^0 e^+\nu_e$ of 1.5.Comment: 10 page postscript file, postscript file also available through http://w4.lns.cornell.edu/public/CLN

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele