Suboptimal light conditions influence source-sink metabolism during flowering

Reliance on carbohydrates during flower forcing was investigated in one early and one late flowering cultivar of azalea (Rhododendron simsii hybrids). Carbohydrate accumulation, invertase activity, and expression of a purported sucrose synthase gene (RsSUS) was monitored during flower forcing under suboptimal (natural) and optimal (supplemental light) light conditions, after a cold treatment (7 degrees C + dark) to break flower bud dormancy. Post-production sucrose metabolism and flowering quality was also assessed. Glucose and fructose concentrations and invertase activity increased in petals during flowering, while sucrose decreased. In suboptimal light conditions RsSUS expression in leaves increased as compared to optimal light conditions, indicating that plants in suboptimal light conditions have a strong demand for carbohydrates. However, carbohydrates in leaves were markedly lower in suboptimal light conditions compared to optimal light conditions. This resulted in poor flowering of plants in suboptimal light conditions. Post production flowering relied on the stored leaf carbon, which could be accumulated under optimal light conditions in the greenhouse. These results show that flower opening in azalea relies on carbohydrates imported from leaves and is source-limiting under suboptimal light conditions

Modeling the epidemiological impact of the UNAIDS 2025 targets to end AIDS as a public health threat by 2030

BACKGROUND: UNAIDS has established new program targets for 2025 to achieve the goal of eliminating AIDS as a public health threat by 2030. This study reports on efforts to use mathematical models to estimate the impact of achieving those targets. METHODS AND FINDINGS: We simulated the impact of achieving the targets at country level using the Goals model, a mathematical simulation model of HIV epidemic dynamics that includes the impact of prevention and treatment interventions. For 77 high-burden countries, we fit the model to surveillance and survey data for 1970 to 2020 and then projected the impact of achieving the targets for the period 2019 to 2030. Results from these 77 countries were extrapolated to produce estimates for 96 others. Goals model results were checked by comparing against projections done with the Optima HIV model and the AIDS Epidemic Model (AEM) for selected countries. We included estimates of the impact of societal enablers (access to justice and law reform, stigma and discrimination elimination, and gender equality) and the impact of Coronavirus Disease 2019 (COVID-19). Results show that achieving the 2025 targets would reduce new annual infections by 83% (71% to 86% across regions) and AIDS-related deaths by 78% (67% to 81% across regions) by 2025 compared to 2010. Lack of progress on societal enablers could endanger these achievements and result in as many as 2.6 million (44%) cumulative additional new HIV infections and 440,000 (54%) more AIDS-related deaths between 2020 and 2030 compared to full achievement of all targets. COVID-19-related disruptions could increase new HIV infections and AIDS-related deaths by 10% in the next 2 years, but targets could still be achieved by 2025. Study limitations include the reliance on self-reports for most data on behaviors, the use of intervention effect sizes from published studies that may overstate intervention impacts outside of controlled study settings, and the use of proxy countries to estimate the impact in countries with fewer than 4,000 annual HIV infections. CONCLUSIONS: The new targets for 2025 build on the progress made since 2010 and represent ambitious short-term goals. Achieving these targets would bring us close to the goals of reducing new HIV infections and AIDS-related deaths by 90% between 2010 and 2030. By 2025, global new infections and AIDS deaths would drop to 4.4 and 3.9 per 100,000 population, and the number of people living with HIV (PLHIV) would be declining. There would be 32 million people on treatment, and they would need continuing support for their lifetime. Incidence for the total global population would be below 0.15% everywhere. The number of PLHIV would start declining by 2023

Ending AIDS as a public health threat by 2030: Time to reset targets for 2025.

Paul De Lay and co-authors introduce a Collection on the design of targets for ending the AIDS epidemic

Plate-boundary deformation associated with the great Sumatra–Andaman earthquake

The Sumatra–Andaman earthquake of 26 December 2004 is the first giant earthquake (moment magnitude M_w > 9.0) to have occurred since the advent of modern space-based geodesy and broadband seismology. It therefore provides an unprecedented opportunity to investigate the characteristics of one of these enormous and rare events. Here we report estimates of the ground displacement associated with this event, using near-field Global Positioning System (GPS) surveys in northwestern Sumatra combined with in situ and remote observations of the vertical motion of coral reefs. These data show that the earthquake was generated by rupture of the Sunda subduction megathrust over a distance of >1,500 kilometres and a width of <150 kilometres. Megathrust slip exceeded 20 metres offshore northern Sumatra, mostly at depths shallower than 30 kilometres. Comparison of the geodetically and seismically inferred slip distribution indicates that ~30 per cent additional fault slip accrued in the 1.5 months following the 500-second-long seismic rupture. Both seismic and aseismic slip before our re-occupation of GPS sites occurred on the shallow portion of the megathrust, where the large Aceh tsunami originated. Slip tapers off abruptly along strike beneath Simeulue Island at the southeastern edge of the rupture, where the earthquake nucleated and where an M_w = 7.2 earthquake occurred in late 2002. This edge also abuts the northern limit of slip in the 28 March 2005 M_w = 8.7 Nias–Simeulue earthquake

Lower edge of locked Main Himalayan Thrust unzipped by the 2015 Gorkha earthquake

Large earthquakes are thought to release strain on previously locked faults. However, the details of how earthquakes are initiated, grow and terminate in relation to pre-seismically locked and creeping patches is unclear ^1-4. The 2015 Mw 7.8 Gorkha, Nepal earthquake occurred close to Kathmandu in a region where the prior pattern of fault locking is well documented ^5. Here we analyze this event using seismological records measured at teleseismic distances and Synthetic Aperture Radar imagery. We show that the earthquake originated northwest of Kathmandu within a cluster of background seismicity that fringes the bottom of the locked portion of the Main Himalayan Thrust fault (MHT). The rupture propagated eastwards for about 140 km, unzipping the lower edge of the locked portion of the fault. High-frequency seismic waves radiated continuously as the slip pulse propagated at about 2.8 km s-1 along this zone of presumably high and heterogeneous pre-¬seismic stress at the seismic-aseismic transition. Eastward unzipping of the fault resumed during the Mw 7.3 aftershock on May 12. The transfer of stress to neighbouring regions during the Gorkha earthquake should facilitate future rupture of the areas of the MHT adjacent and up-dip of the Gorkha earthquake rupture.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ngeo251

Spotlights on Contemporary Family Life

Spotlights on Contemporary Family Life covers four issues of cross-cutting importance to families Structures and forms of families: issues relating to a diversification of families away from the ‘traditional nuclear family form’ are relatively uncontroversial from an academic perspective, but much more so for policy makers and family associations. Chapter 1 provides a thorough overview of the state of contemporary European families. Solidarities in families: too often the issue of an ‘ageing society’ is simply reduced to the problem of over-burdening social care systems, but longevity also represents opportunities for new kinds of solidarities inside families and family networks, and new relations between family members – not to mention the satisfaction felt by people who can continue to live fulfilling and rewarding lives long after they’re considered ‘elderly’. Chapter 2 gives voice to authors who identify these new opportunities and challenges. Demographic change: women are having fewer children and having them later in life. Having children is now a conscious decision and fertility rates have declined below the level required to sustain our current populations. At the same time we witness the ‘greying’ of Europe, which brings with it a whole host of opportunities and challenges. Chapter 3 raises important issues for policy makers today. Volunteering: inspired by family associations who could not survive without the support of volunteers, this chapter gives an overview of what’s known - and what isn’t - about volunteering. Coinciding with the European Year of Volunteering 2011, this chapter takes a timely look at the efforts that families put into volunteering across Europe and the important benefits that Europe gains from all of this combined voluntary effort. Linden Farrer and William Lay work for the Confederation of Family Organisations in the European Union (COFACE). This publication was produced by FAMILYPLATFORM, a project funded by the European Commission

Pattern and levels of spending allocated to HIV prevention programs in low- and middle-income countries

<p>Abstract</p> <p>Background</p> <p>AIDS continues to spread at an estimated 2.6 new million infections per year, making the prevention of HIV transmission a critical public health issue. The dramatic growth in global resources for AIDS has produced a steady scale-up in treatment and care that has not been equally matched by preventive services. This paper is a detailed analysis of how countries are choosing to spend these more limited prevention funds.</p> <p>Methods</p> <p>We analyzed prevention spending in 69 low- and middle-income countries with a variety of epidemic types, using data from national domestic spending reports. Spending information was from public and international sources and was analyzed based on the National AIDS Spending Assessment (NASA) methods and classifications.</p> <p>Results</p> <p>Overall, prevention received 21% of HIV resources compared to 53% of funding allocated to treatment and care. Prevention relies primarily on international donors, who accounted for 65% of all prevention resources and 93% of funding in low-income countries. For the subset of 53 countries that provided detailed spending information, we found that 60% of prevention resources were spent in five areas: communication for social and behavioral change (16%), voluntary counselling and testing (14%), prevention of mother-to-child transmission (13%), blood safety (10%) and condom programs (7%). Only 7% of funding was spent on most-at-risk populations and less than 1% on male circumcision. Spending patterns did not consistently reflect current evidence and the HIV specific transmission context of each country.</p> <p>Conclusions</p> <p>Despite recognition of its importance, countries are not allocating resources in ways that are likely to achieve the greatest impact on prevention across all epidemic types. Within prevention spending itself, a greater share of resources need to be matched with interventions that approximate the specific needs and drivers of each country's epidemic.</p

Comparative Analysis of Pyrosequencing and a Phylogenetic Microarray for Exploring Microbial Community Structures in the Human Distal Intestine

Background Variations in the composition of the human intestinal microbiota are linked to diverse health conditions. High-throughput molecular technologies have recently elucidated microbial community structure at much higher resolution than was previously possible. Here we compare two such methods, pyrosequencing and a phylogenetic array, and evaluate classifications based on two variable 16S rRNA gene regions. Methods and Findings Over 1.75 million amplicon sequences were generated from the V4 and V6 regions of 16S rRNA genes in bacterial DNA extracted from four fecal samples of elderly individuals. The phylotype richness, for individual samples, was 1,400–1,800 for V4 reads and 12,500 for V6 reads, and 5,200 unique phylotypes when combining V4 reads from all samples. The RDP-classifier was more efficient for the V4 than for the far less conserved and shorter V6 region, but differences in community structure also affected efficiency. Even when analyzing only 20% of the reads, the majority of the microbial diversity was captured in two samples tested. DNA from the four samples was hybridized against the Human Intestinal Tract (HIT) Chip, a phylogenetic microarray for community profiling. Comparison of clustering of genus counts from pyrosequencing and HITChip data revealed highly similar profiles. Furthermore, correlations of sequence abundance and hybridization signal intensities were very high for lower-order ranks, but lower at family-level, which was probably due to ambiguous taxonomic groupings. Conclusions The RDP-classifier consistently assigned most V4 sequences from human intestinal samples down to genus-level with good accuracy and speed. This is the deepest sequencing of single gastrointestinal samples reported to date, but microbial richness levels have still not leveled out. A majority of these diversities can also be captured with five times lower sampling-depth. HITChip hybridizations and resulting community profiles correlate well with pyrosequencing-based compositions, especially for lower-order ranks, indicating high robustness of both approaches. However, incompatible grouping schemes make exact comparison difficult

Epigenetics and developmental programming of welfare and production traits in farm animals

The concept that postnatal health and development can be influenced by events that occur in utero originated from epidemiological studies in humans supported by numerous mechanistic (including epigenetic) studies in a variety of model species. Referred to as the ‘developmental origins of health and disease’ or ‘DOHaD’ hypothesis, the primary focus of large-animal studies until quite recently had been biomedical. Attention has since turned towards traits of commercial importance in farm animals. Herein we review the evidence that prenatal risk factors, including suboptimal parental nutrition, gestational stress, exposure to environmental chemicals and advanced breeding technologies, can determine traits such as postnatal growth, feed efficiency, milk yield, carcass composition, animal welfare and reproductive potential. We consider the role of epigenetic and cytoplasmic mechanisms of inheritance, and discuss implications for livestock production and future research endeavours. We conclude that although the concept is proven for several traits, issues relating to effect size, and hence commercial importance, remain. Studies have also invariably been conducted under controlled experimental conditions, frequently assessing single risk factors, thereby limiting their translational value for livestock production. We propose concerted international research efforts that consider multiple, concurrent stressors to better represent effects of contemporary animal production systems

Durvalumab Plus Carboplatin/Paclitaxel Followed by Maintenance Durvalumab With or Without Olaparib as First-Line Treatment for Advanced Endometrial Cancer: The Phase III DUO-E Trial

PURPOSE Immunotherapy and chemotherapy combinations have shown activity in endometrial cancer, with greater benefit in mismatch repair (MMR)-deficient (dMMR) than MMR-proficient (pMMR) disease. Adding a poly(ADP-ribose) polymerase inhibitor may improve outcomes, especially in pMMR disease. METHODS This phase III, global, double-blind, placebo-controlled trial randomly assigned eligible patients with newly diagnosed advanced or recurrent endometrial cancer 1:1:1 to: carboplatin/paclitaxel plus durvalumab placebo followed by placebo maintenance (control arm); carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib placebo (durvalumab arm); or carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib (durvalumab + olaparib arm). The primary end points were progression-free survival (PFS) in the durvalumab arm versus control and the durvalumab + olaparib arm versus control. RESULTS Seven hundred eighteen patients were randomly assigned. In the intention-to-treat population, statistically significant PFS benefit was observed in the durvalumab (hazard ratio [HR], 0.71 [95% CI, 0.57 to 0.89]; P = .003) and durvalumab + olaparib arms (HR, 0.55 [95% CI, 0.43 to 0.69]; P < .0001) versus control. Prespecified, exploratory subgroup analyses showed PFS benefit in dMMR (HR [durvalumab v control], 0.42 [95% CI, 0.22 to 0.80]; HR [durvalumab + olaparib v control], 0.41 [95% CI, 0.21 to 0.75]) and pMMR subgroups (HR [durvalumab v control], 0.77 [95% CI, 0.60 to 0.97]; HR [durvalumab + olaparib v control] 0.57; [95% CI, 0.44 to 0.73]); and in PD-L1-positive subgroups (HR [durvalumab v control], 0.63 [95% CI, 0.48 to 0.83]; HR [durvalumab + olaparib v control], 0.42 [95% CI, 0.31 to 0.57]). Interim overall survival results (maturity approximately 28%) were supportive of the primary outcomes (durvalumab v control: HR, 0.77 [95% CI, 0.56 to 1.07]; P = .120; durvalumab + olaparib v control: HR, 0.59 [95% CI, 0.42 to 0.83]; P = .003). The safety profiles of the experimental arms were generally consistent with individual agents. CONCLUSION Carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab with or without olaparib demonstrated a statistically significant and clinically meaningful PFS benefit in patients with advanced or recurrent endometrial cancer