Exploring the Feasibility of Service Integration in a Low-Income Setting: A Mixed Methods Investigation into Different Models of Reproductive Health and HIV Care in Swaziland.

Integrating reproductive health (RH) with HIV care is a policy priority in high HIV prevalence settings, despite doubts surrounding its feasibility and varying evidence of effects on health outcomes. The process and outcomes of integrated RH-HIV care were investigated in Swaziland, through a comparative case study of four service models, ranging from fully integrated to fully stand-alone HIV services, selected purposively within one town. A client exit survey (n=602) measured integrated care received and unmet family planning (FP) needs. Descriptive statistics were used to assess the degree of integration per clinic and client demand for services. Logistic regression modelling was used to test the hypothesis that clients at more integrated sites had lower unmet FP needs than clients in a stand-alone site. Qualitative methods included in-depth interviews with clients and providers to explore contextual factors influencing the feasibility of integrated RH-HIV care delivery; data were analysed thematically, combining deductive and inductive approaches. Results demonstrated that clinic models were not as integrated in practice as had been claimed. Fragmentation of HIV care was common. Services accessed per provider were no higher at the more integrated clinics compared to stand-alone models (p>0.05), despite reported demand. While women at more integrated sites received more FP and pregnancy counselling than stand-alone models, they received condoms (a method of choice) less often, and there was no statistical evidence of difference in unmet FP needs by model of care. Multiple contextual factors influenced integration practices, including provider de-skilling within sub-specialist roles; norms of task-oriented routinised HIV care; perceptions of heavy client loads; imbalanced client-provider interactions hindering articulation of RH needs; and provider motivation challenges. Thus, despite institutional support, factors related to the social context of care inhibited provision of fully integrated RH-HIV services in these clinics. Programmes should move beyond simplistic training and equipment provision if integrated care interventions are to be sustained

Study of Bc+B_c^+ decays to the K+K−π+K^+K^-\pi^+ final state and evidence for the decay Bc+→χc0π+B_c^+\to\chi_{c0}\pi^+

A study of $B_c^+\to K^+K^-\pi^+$ decays is performed for the first time using data corresponding to an integrated luminosity of 3.0 $\mathrm{fb}^{-1}$ collected by the LHCb experiment in $pp$ collisions at centre-of-mass energies of $7$ and $8$ TeV. Evidence for the decay $B_c^+\to\chi_{c0}(\to K^+K^-)\pi^+$ is reported with a significance of 4.0 standard deviations, resulting in the measurement of $\frac{\sigma(B_c^+)}{\sigma(B^+)}\times\mathcal{B}(B_c^+\to\chi_{c0}\pi^+)$ to be $(9.8^{+3.4}_{-3.0}(\mathrm{stat})\pm 0.8(\mathrm{syst}))\times 10^{-6}$. Here $\mathcal{B}$ denotes a branching fraction while $\sigma(B_c^+)$ and $\sigma(B^+)$ are the production cross-sections for $B_c^+$ and $B^+$ mesons. An indication of $\bar b c$ weak annihilation is found for the region $m(K^-\pi^+)<1.834\mathrm{\,Ge\kern -0.1em V\!/}c^2$, with a significance of 2.4 standard deviations.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2016-022.html, link to supplemental material inserted in the reference

Exploring Functional β-Cell Heterogeneity In Vivo Using PSA-NCAM as a Specific Marker

BACKGROUND:The mass of pancreatic beta-cells varies according to increases in insulin demand. It is hypothesized that functionally heterogeneous beta-cell subpopulations take part in this process. Here we characterized two functionally distinct groups of beta-cells and investigated their physiological relevance in increased insulin demand conditions in rats. METHODS:Two rat beta-cell populations were sorted by FACS according to their PSA-NCAM surface expression, i.e. beta(high) and beta(low)-cells. Insulin release, Ca(2+) movements, ATP and cAMP contents in response to various secretagogues were analyzed. Gene expression profiles and exocytosis machinery were also investigated. In a second part, beta(high) and beta(low)-cell distribution and functionality were investigated in animal models with decreased or increased beta-cell function: the Zucker Diabetic Fatty rat and the 48 h glucose-infused rat. RESULTS:We show that beta-cells are heterogeneous for PSA-NCAM in rat pancreas. Unlike beta(low)-cells, beta(high)-cells express functional beta-cell markers and are highly responsive to various insulin secretagogues. Whereas beta(low)-cells represent the main population in diabetic pancreas, an increase in beta(high)-cells is associated with gain of function that follows sustained glucose overload. CONCLUSION:Our data show that a functional heterogeneity of beta-cells, assessed by PSA-NCAM surface expression, exists in vivo. These findings pinpoint new target populations involved in endocrine pancreas plasticity and in beta-cell defects in type 2 diabetes

Epigenetic regulation of centromeric chromatin: old dogs, new tricks?

The assembly of just a single kinetochore at the centromere of each sister chromatid is essential for accurate chromosome segregation during cell division. Surprisingly, despite their vital function, centromeres show considerable plasticity with respect to their chromosomal locations and activity. The establishment and maintenance of centromeric chromatin, and therefore the location of kinetochores, is epigenetically regulated. The histone H3 variant CENP-A is the key determinant of centromere identity and kinetochore assembly. Recent studies have identified many factors that affect CENP-A localization, but their precise roles in this process are unknown. We build on these advances and on new information about the timing of CENP-A assembly during the cell cycle to propose new models for how centromeric chromatin is established and propagated

ER stress in rodent islets of langerhans is concomitant with obesity and β-cell compensation but not with β-cell dysfunction and diabetes

Objective: The objective of this study was to determine whether ER stress correlates with β-cell dysfunction in obesity-associated diabetes. Methods: Quantitative RT-PCR and western blot analysis were used to investigate changes in the expression of markers of ER stress, the unfolded protein response (UPR) and β-cell function in islets isolated from (1) non-diabetic Zucker obese (ZO) and obese female Zucker diabetic fatty (fZDF) rats compared with their lean littermates and from (2) high-fat-diet-fed fZDF rats (HF-fZDF), to induce diabetes, compared with age-matched non-diabetic obese fZDF rats. Results: Markers of an adaptive ER stress/UPR and β-cell function are elevated in islets isolated from ZO and fZDF rats compared with their lean littermates. In islets isolated from HF-fZDF rats, there was no significant change in the expression of markers of ER stress compared with age matched, obese, non-diabetic fZDF rats. Conclusions: These results provide evidence that obesity-induced activation of the UPR is an adaptive response for increasing the ER folding capacity to meet the increased demand for insulin. As ER stress is not exacerbated in high-fat-diet-induced diabetes, we suggest that failure of the islet to mount an effective adaptive UPR in response to an additional increase in insulin demand, rather than chronic ER stress, may ultimately lead to β-cell failure and hence diabetes

Measurement of the B0s →J/ψη lifetime

Using a data set corresponding to an integrated luminosity of 3 fb−1, collected by the LHCb experiment in pp collisions at centre-of-mass energies of 7 and 8 TeV, the effective lifetime in the Bs0→J/ψη decay mode, τeff, is measured to be τeff=1.479±0.034 (stat)±0.011 (syst) ps. Assuming CP conservation, τeff corresponds to the lifetime of the light Bs0 mass eigenstate. This is the first measurement of the effective lifetime in this decay mode

Observation of B+c → D0K+ decays

Using proton-proton collision data corresponding to an integrated luminosity of 3.0 fb−1, recorded by the LHCb detector at center-of-mass energies of 7 and 8 TeV, the B+ c → D0K+ decay is observed with a statistical significance of 5.1 standard deviations. By normalizing to B+ → D¯ 0π+ decays, a measurement of the branching fraction multiplied by the production rates for B+ c relative to B+ mesons in the LHCb acceptance is obtained, R D 0 K = ( f c / f u ) × B ( B + c → D 0 K + ) = ( 9. 3 + 2.8 − 2.5 ± 0.6 ) × 10 − 7, where the first uncertainty is statistical and the second is systematic. This decay is expected to proceed predominantly through weak annihilation and penguin amplitudes, and is the first B+ c decay of this nature to be observed

Measurement of the CKM angle γ\gamma using B0→DK∗0B^0 \rightarrow D K^{*0} with D→KS0π+π−D \rightarrow K^0_S \pi^+ \pi^- decays

A model-dependent amplitude analysis of the decay $B^0\rightarrow D(K^0_S\pi^+\pi^-) K^{*0}$ is performed using proton-proton collision data corresponding to an integrated luminosity of 3.0fb$^{-1}$, recorded at $\sqrt{s}=7$ and $8 TeV$ by the LHCb experiment. The CP violation observables $x_{\pm}$ and $y_{\pm}$, sensitive to the CKM angle $\gamma$, are measured to be \begin{eqnarray*} x_- &=& -0.15 \pm 0.14 \pm 0.03 \pm 0.01, y_- &=& 0.25 \pm 0.15 \pm 0.06 \pm 0.01, x_+ &=& 0.05 \pm 0.24 \pm 0.04 \pm 0.01, y_+ &=& -0.65^{+0.24}_{-0.23} \pm 0.08 \pm 0.01, \end{eqnarray*} where the first uncertainties are statistical, the second systematic and the third arise from the uncertainty on the $D\rightarrow K^0_S \pi^+\pi^-$ amplitude model. These are the most precise measurements of these observables. They correspond to $\gamma=(80^{+21}_{-22})^{\circ}$ and $r_{B^0}=0.39\pm0.13$, where $r_{B^0}$ is the magnitude of the ratio of the suppressed and favoured $B^0\rightarrow D K^+ \pi^-$ decay amplitudes, in a $K\pi$ mass region of $\pm50 MeV$ around the $K^*(892)^0$ mass and for an absolute value of the cosine of the $K^{*0}$ decay angle larger than $0.4$.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2016-007.htm

Model-independent measurement of mixing parameters in D0 → K S 0 π+π− decays

The first model-independent measurement of the charm mixing parameters in the decay D 0 → K S 0 π + π − is reported, using a sample of pp collision data recorded by the LHCb experiment, corresponding to an integrated luminosity of 1.0 fb−1 at a centre-of-mass energy of 7 TeV. The measured values are x=(−0.86±0.53±0.17)×10−2,y=(+0.03±0.46±0.13)×10−2, x=(−0.86±0.53±0.17)×10−2,y=(+0.03±0.46±0.13)×10−2, where the first uncertainties are statistical and include small contributions due to the external input for the strong phase measured by the CLEO collaboration, and the second uncertainties are systematic

Measurement of the B0s→μ+μ− Branching Fraction and Effective Lifetime and Search for B0→μ+μ− Decays

See paper for full list of authors - All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2017-001.html - Submitted to Phys. Rev. Lett.International audienceA search for the rare decays B0s→μ+μ− and B0→μ+μ− is performed at the LHCb experiment using data collected in pp collisions corresponding to a total integrated luminosity of 4.4 fb−1. An excess of B0s→μ+μ− decays is observed with a significance of 7.8 standard deviations, representing the first observation of this decay in a single experiment. The branching fraction is measured to be B(B0s→μ+μ−)=(3.0±0.6+0.3−0.2)×10−9, where the first uncertainty is statistical and the second systematic. The first measurement of the B0s→μ+μ− effective lifetime, τ(B0s→μ+μ−)=2.04±0.44±0.05 ps, is reported. No significant excess of B0→μ+μ− decays is found and a 95 % confidence level upper limit, B(B0→μ+μ−)<3.4×10−10, is determined. All results are in agreement with the Standard Model expectations