Age-Restriction of a Validated Risk Scoring Tool Better Predicts HIV Acquisition in South African Women: CAPRISA 004.

We examined the predictive ability of the VOICE risk screening tool among adolescent girls and young women at heightened HIV risk in urban and peri-urban Kwa-Zulu-Natal, South Africa. Using participant data from CAPRISA 004's control arm (N = 444), we applied the initial VOICE risk screening score (IRS), a modified risk score (MRS) based on predictive and non-predictive variables in our data, and age-restricted (AIRS and AMRS, respectively). We estimated incidence rates, 95% confidence bounds, sensitivity, specificity, negative and positive predictive values and area under the curve (AUC). The sample's HIV incidence rate was 9.1/100 Person-Years [95% CI 6.9-11.7], resulting from 60 seroconversions (60/660.7 Person-Years). The IRS' ≥ 8 cutpoint produced moderate discrimination [AUC = 0.66 (0.54-0.74), sensitivity = 63%, specificity = 57%]. Restricting to age < 25 years improved the score's predictive ability (AIRS: AUC = 0.69, AMRS: AUC = 0.70), owing mainly to male partner having other partners and HSV-2. The risk tool predicted HIV acquisition at a higher cutpoint in this sample than in the initial VOICE analysis. After age-stratification, fewer variables were needed for maintaining score's predictiveness. In this high incidence setting, risk screening may still improve the efficiency or effectiveness of prevention counseling services. However, PrEP should be offered to all prevention-seeking individuals, regardless of risk ascertainment.

Ro-vibrational level dependence of the radiative lifetime of the Na241Σg + shelf state.

We report on calculations-using the LEVEL and BCONT programs by Le Roy, the latter of which is a version modified by B. McGeehan-of the dependence of the radiative lifetime of the Na2 sodium dimer 41Σg + shelf-state on the initial vibrational and rotational level for corresponding quantum numbers of 0 ≤ v ≤ 75 and 0 ≤ J ≤ 90, respectively. We also present experimental lifetime values for 43 < v < 64, averaged over J = 19 and 21, obtained by a delayed pump-probe method using a previously described molecular beam and time-of-flight apparatus. Our calculated results are based on all possible dipole allowed transitions (to the 21Σu +, 1(B)1Πu, and 1(A)1Σu + electronic states) terminating into bound as well as free final states. The shelf of the initial electronic state is a consequence of configuration interaction with the lowest Na+-Na- ion-pair potential and occurs, for the rotationless molecule, at the vibrational level v = 52. From the 41Σg + vibrational ground state to the shelf, the calculated lifetimes increase monotonically by a factor of about 3.8. Beyond around v = 52, depending on rotational excitation, the lifetimes decrease, settling to a value intermediate to the maximum and the minimum at v = 0. Within error bars and in the range available, our experimental data are compatible with these findings. In addition, our calculations reveal unusual and pronounced oscillatory variation of the lifetime with rotational quantum numbers for fixed vibrational levels above-but not below-the shelf. We discuss our findings in terms of the appropriate transition dipole moments and wavefunctions and provide a detailed comparison to recent lifetime calculations of sodium dimer ion-pair states [Sanli et al., J. Chem. Phys. 143, 104304 (2015)].

Use of contraceptives, high risk births and under-five mortality in Sub Saharan Africa: evidence from Kenyan (2014) and Zimbabwean (2011) demographic health surveys.

BACKGROUND: Increasing uptake of modern contraception is done to alleviate maternal and infant mortality in poor countries. We describe prevalence of contraceptive use, high risk births, under-five mortality and their risk factors in Kenya and Zimbabwe. METHODS: This was a cross-sectional analysis on DHS data from Kenya (2014) and Zimbabwe (2011) for women aged 15-49. Geospatial mapping was used to compare the proportions of the following outcomes: current use of contraceptives, high-risk births, and under-5 mortality at regional levels after applying sample weights to account for disproportionate sampling and non-responses. Multivariate risk factors for the outcomes were evaluated by multilevel logistic regression and reported as adjusted odds ratios (aOR). RESULTS: A total of 40,250 (31,079 Kenya vs. 9171 Zimbabwe) women were included in this analysis. Majority were aged 18-30 years (47%), married/cohabiting (61%) and unemployed (60%). Less than half were using contraceptives (36% Kenya vs. 41% Zimbabwe). Spatial maps, especially in the Kenyan North-eastern region, showed an inverse correlation in the current use of contraceptives with high risk births and under-5 mortality. At individual level, women that had experienced high risk births were likely to have attained secondary education in both Kenya (aOR = 5.20, 95% CI: 3.86-7.01) and Zimbabwe (aOR = 1.63, 95% CI: 1.08-2.25). In Kenya, high household wealth was associated with higher contraceptive use among both women who had high risk births (aOR: 1.72, 95% CI: 1.41-2.11) and under-5 mortality (aOR: 1.66, 95% CI: 1.27-2.16). Contraceptive use was protective against high risk births in Zimbabwe only (aOR: 0.79, 95% CI: 0.68-0.92) and under-five mortality in both Kenya (aOR: 0.79, 95% CI: 0.70-0.89) and Zimbabwe (aOR: 0.71, 95% CI: 0.61-0.83). Overall, community levels factors were not strong predictors of the three main outcomes. CONCLUSIONS: There is a high unmet need of contraception services. Geospatial mapping might be useful to policy makers in identifying areas of greatest need. Increasing educational opportunities and economic empowerment for women could yield better health outcomes.

Time-resolved photoionization spectroscopy of mixed Rydberg-valence states: indole case study.

Time-resolved photoelectron imaging was used to study non-adiabatic relaxation dynamics in gas-phase indole following photo-excitation at 267 nm and 258 nm. Our data analysis was supported by various ab initio calculations using both coupled cluster and density functional methods. The highly differential energy- and angle-resolved information provided by our experimental approach provides extremely subtle details of the complex interactions occurring between several low-lying electronically excited states. In particular, new insight into the role and fate of the mixed Rydberg-valence 3s/πσ* state is revealed. This includes population residing on the excited state surface at large N-H separations for a relatively long period of time (∼1 ps) prior to dissociation and/or internal conversion. Our findings may, in part, be rationalized by considering the rapid evolution of this state's electronic character as the N-H stretching coordinate is extended - as extensively demonstrated in the supporting theory. Overall, our findings highlight a number of important general caveats regarding the nature of mixed Rydberg-valence excited states, their spectral signatures and detection sensitivity in photoionization measurements, and the evaluation of their overall importance in mediating electronic relaxation in a wide range of small model-chromophore systems providing bio-molecular analogues - a topic of considerable interest within the chemical dynamics community over the last decade.

Crisis resolution and home treatment in the UK: A survey of model fidelity using a novel review methodology.

Crisis resolution teams (CRTs) provide treatment at home to people experiencing mental health crises, as an alternative to hospital admission. Previous UK research, based on self-report surveys, suggests that a loosely specified model has resulted in wide variations in CRTs' service delivery, organization and outcomes. A fidelity scale (developed through evidence review and stakeholder consensus) provided a means of objectively measuring adherence to a model of good practice for CRTs, via one-day fidelity reviews of UK crisis teams. Reviews included interviews with service users, carers, staff and managers, and examination of data, policies, protocols and anonymized case notes. Of the 75 teams reviewed, 49 (65%) were assessed as being moderate fidelity and the rest as low fidelity, with no team achieving high fidelity. The median score was 122 (range: 73-151; inter-quartile range: 111-132). Teams achieved higher scores on items about structure and organization, for example ease of referral, medication and safety systems, but scored poorly on items about the content of care and interventions. Despite a national mandate to implement the CRT model, there are wide variations in implementation in the UK and no teams in our sample achieved overall high fidelity. This suggests that a mandatory national policy is not in itself sufficient to achieve good quality implementation of a service model. The CRT Fidelity Scale provides a feasible and acceptable means to objectively assess model fidelity in CRTs. There is a need for development and testing of interventions to enhance model fidelity and facilitate improvements to these services.

The direction of measured face aftereffects.

Prolonged viewing of a face can result in a change of our perception of subsequent faces. This process of adaptation is believed to be functional and to reflect optimization-driven changes in the neural encoding. Because it is believed to target the neural systems underlying face processing, the measurement of face aftereffects is seen as a powerful behavioral technique that can provide deep insights into our facial encoding. Face identity aftereffects have typically been measured by assessing the way in which adaptation changes the perception of images from a test sequence, the latter commonly derived from morphing between two base images. The current study asks to what extent such face aftereffects are driven by the test sequence used to measure them. Using subjects trained to respond either to identity of expression, we examined the effects of identity and expression adaptation on test stimuli that varied in both identity and expression. We found that face adaptation produced measured aftereffects that were congruent with the adaptation stimulus; the composition of the test sequences did not affect the measured direction of the face aftereffects. Our results support the view that face adaptation studies can meaningfully tap into the intrinsically multidimensional nature of our representation of facial identity.

Effect of water content on the glass transition temperature of mixtures of sugars, polymers, and penetrating cryoprotectants in physiological buffer.

Long-term storage of viable mammalian cells is important for applications ranging from in vitro fertilization to cell therapy. Cryopreservation is currently the most common approach, but storage in liquid nitrogen is relatively costly and the requirement for low temperatures during shipping is inconvenient. Desiccation is an alternative strategy with the potential to enable viable cell preservation at more convenient storage temperatures without the need for liquid nitrogen. To achieve stability during storage in the dried state it is necessary to remove enough water that the remaining matrix forms a non-crystalline glassy solid. Thus, the glass transition temperature is a key parameter for design of cell desiccation procedures. In this study, we have investigated the effects of moisture content on the glass transition temperature (Tg) of mixtures of sugars (trehalose or raffinose), polymers (polyvinylpyrrolidone or Ficoll), penetrating cryoprotectants (ethylene glycol, propylene glycol, or dimethyl sulfoxide), and phosphate buffered saline (PBS) solutes. Aqueous solutions were dried to different moisture contents by equilibration with saturated salt solutions, or by baking at 95°C. The glass transition temperatures of the dehydrated samples were then measured by differential scanning calorimetry. As expected, Tg increased with decreasing moisture content. For example, in a desiccation medium containing 0.1 M trehalose in PBS, Tg ranged from about 360 K for a completely dry sample to about 220 K at a water mass fraction of 0.4. Addition of polymers to the solutions increased Tg, while addition of penetrating cryoprotectants decreased Tg. Our results provide insight into the relationship between relative humidity, moisture content and glass transition temperature for cell desiccation solutions containing sugars, polymers and penetrating cryoprotectants.

Accelerating access and scale-up of optimized ART in low-income and middle-income countries: a call for a coordinated end-to-end approach.

PURPOSE OF REVIEW: To discuss how aligning the collective power of scientists, regulators, drug companies, donors, implementers and advocates to achieve a single goal - accelerating access to simpler, safer, more robust and more affordable HIV treatment - can rapidly advance antiretroviral optimization efforts and enable scale-up. RECENT FINDINGS: Harmonization of traditionally sequential processes can address the delays commonly experienced in introducing new products to low-income and middle-income countries, by facilitating an 'end-to-end' approach that mitigates risk and encourages early planning for all aspects of product introduction. SUMMARY: Planning with the 'end-in-mind' can facilitate healthy markets, benefit the application of new technologies, and accelerate the development of improved products in parallel (versus traditionally sequential efforts).

VEGF-Mediated Induction of PRD1-BF1/Blimp1 Expression Sensitizes Tumor Vasculature to Oncolytic Virus Infection.

Oncolytic viruses designed to attack malignant cells can in addition infect and destroy tumor vascular endothelial cells. We show here that this expanded tropism of oncolytic vaccinia virus to the endothelial compartment is a consequence of VEGF-mediated suppression of the intrinsic antiviral response. VEGF/VEGFR2 signaling through Erk1/2 and Stat3 leads to upregulation, nuclear localization, and activation of the transcription repressor PRD1-BF1/Blimp1. PRD1-BF1 does not contribute to the mitogenic effects of VEGF, but directly represses genes involved in type I interferon (IFN)-mediated antiviral signaling. In vivo suppression of VEGF signaling diminishes PRD1-BF1/Blimp1 expression in tumor vasculature and inhibits intravenously administered oncolytic vaccinia delivery to and consequent spread within the tumor.

The relationship between therapeutic alliance and service user satisfaction in mental health inpatient wards and crisis house alternatives: a cross-sectional study.

BACKGROUND: Poor service user experiences are often reported on mental health inpatient wards. Crisis houses are an alternative, but evidence is limited. This paper investigates therapeutic alliances in acute wards and crisis houses, exploring how far stronger therapeutic alliance may underlie greater client satisfaction in crisis houses. METHODS AND FINDINGS: Mixed methods were used. In the quantitative component, 108 crisis house and 247 acute ward service users responded to measures of satisfaction, therapeutic relationships, informal peer support, recovery and negative events experienced during the admission. Linear regressions were conducted to estimate the association between service setting and measures, and to model the factors associated with satisfaction. Qualitative interviews exploring therapeutic alliances were conducted with service users and staff in each setting and analysed thematically. RESULTS: We found that therapeutic alliances, service user satisfaction and informal peer support were greater in crisis houses than on acute wards, whilst self-rated recovery and numbers of negative events were lower. Adjusted multivariable analyses suggest that therapeutic relationships, informal peer support and negative experiences related to staff may be important factors in accounting for greater satisfaction in crisis houses. Qualitative results suggest factors that influence therapeutic alliances include service user perceptions of basic human qualities such as kindness and empathy in staff and, at service level, the extent of loss of liberty and autonomy. CONCLUSIONS AND IMPLICATIONS: We found that service users experience better therapeutic relationships and higher satisfaction in crisis houses compared to acute wards, although we cannot exclude the possibility that differences in service user characteristics contribute to this. This finding provides some support for the expansion of crisis house provision. Further research is needed to investigate why acute ward service users experience a lack of compassion and humanity from ward staff and how this could be changed.