Controlling Kernels and Linked Lists Using Dowse

Futurists agree that heterogeneous modalities are an interesting new topic in the field of hardware and architecture, and researchers concur. Here, authors confirm the simulation of the memory bus. In this paper, we construct a novel methodology for the deployment of massive multiplayer online role-playing games (Dowse), which we use to verify that the Internet and e-business can collaborate to accomplish this objective

Priority Medicines for Maternal and Child Health: A Global Survey of National Essential Medicines Lists

BACKGROUND: In April 2011, the World Health Organization (WHO) published a list of "priority medicines" for maternal and child health based on 1) the global burden of disease and 2) evidence of efficacy and safety. The objective of this study was to examine the occurrence of these priority medicines on national essential medicines lists. METHODS AND FINDINGS: All essential medicines lists published since 1999 were selected from the WHO website collection. The most-up-to date list for each country was then selected, resulting in 89 unique country lists. Each list was evaluated for inclusion of medicines (chemical entity, concentration, and dosage form) on the Priority Medicines List. There was global variation in the listing of the Priority Medicines. The most frequently listed medicine was paracetamol, on 94% (84/89) of lists. Sodium chloride, gentamicin and oral rehydration solution were on 93% (83/89) of lists. The least frequently listed medicine was the children's antimalarial rectal artesunate, on 8% of lists (7/89); artesunate injection was on 16% (14/89) of lists. Pediatric artemisinin combination therapy, as dispersible tablets or flexible oral solid dosage form, appeared on 36% (32/89) of lists. Procaine benzylpenicillin, for treatment of pediatric pneumonia and neonatal sepsis, was on 50% (45/89) of the lists. Zinc, for treatment of diarrhoea in children, was included on only 15% (13/89) of lists. For prevention and treatment of postpartum hemorrhage in women, oxytocin was more prevalent on the lists than misoprostol; they were included on 55 (62%) and 31 (35%) of lists, respectively. Cefixime, for treatment of uncomplicated anogenital gonococcal infection in woman was on 26% (23/89) of lists. Magnesium sulfate injection for treatment of severe pre-eclampsia and eclampsia was on 50% (45/89) of the lists. CONCLUSIONS: The findings suggest that countries need to urgently amend their lists to provide all priority medicines as part of the efforts to improve maternal and child health

Beyond dehydrocoupling:group 2 mediated boron-nitrogen desilacoupling

The alkaline earth bis(trimethylsilyl)amides, [Ae{N(SiMe3)2}2(THF)2] [Ae = Mg, Ca, Sr], are effective pre-catalysts for boron-nitrogen bond formation through the desilacoupling of amines, RR’NH (R = alkyl, aryl; R′ = H, alkyl, aryl), and pinBSiMe2Ph. This reactivity also yields a stoichiometric quantity of Me2PhSiH and provides the first example of a catalytic main group element-element coupling that is not dependent on the concurrent elimination of H2

Vaccine-elicited human T cells recognizing conserved protein regions inhibit HIV-1

Virus diversity and escape from immune responses are the biggest challenges to the development of an effective vaccine against HIV-1. We hypothesized that T-cell vaccines targeting the most conserved regions of the HIV-1 proteome, which are common to most variants and bear fitness costs when mutated, will generate effectors that efficiently recognize and kill virus-infected cells early enough after transmission to potentially impact on HIV-1 replication and will do so more efficiently than whole protein-based T-cell vaccines. Here, we describe the first-ever administration of conserved immunogen vaccines vectored using prime-boost regimens of DNA, simian adenovirus and modified vaccinia virus Ankara to uninfected UK volunteers. The vaccine induced high levels of effector T cells that recognized virus-infected autologous CD4+ cells and inhibited HIV-1 replication by up to 5.79 log10. The virus inhibition was mediated by both Gag- and Pol- specific effector CD8+ T cells targeting epitopes that are typically subdominant in natural infection. These results provide proof of concept for using a vaccine to target T cells at conserved epitopes, showing that these T cells can control HIV-1 replication in vitro

Comprehensive quality assessment for aphasia rehabilitation after stroke: Protocol for a multicentre, mixed-methods study

INTRODUCTION: People with aphasia following stroke experience disproportionally poor outcomes, yet there is no comprehensive approach to measuring the quality of aphasia services. The Meaningful Evaluation of Aphasia SeRvicES (MEASuRES) minimum dataset was developed in partnership with people with lived experience of aphasia, clinicians and researchers to address this gap. It comprises sociodemographic characteristics, quality indicators, treatment descriptors and outcome measurement instruments. We present a protocol to pilot the MEASuRES minimum dataset in clinical practice, describe the factors that hinder or support implementation and determine meaningful thresholds of clinical change for core outcome measurement instruments. METHODS AND ANALYSIS: This research aims to deliver a comprehensive quality assessment toolkit for poststroke aphasia services in four studies. A multicentre pilot study (study 1) will test the administration of the MEASuRES minimum dataset within five Australian health services. An embedded mixed-methods process evaluation (study 2) will evaluate the performance of the minimum dataset and explore its clinical applicability. A consensus study (study 3) will establish consumer-informed thresholds of meaningful change on core aphasia outcome constructs, which will then be used to establish minimal important change values for corresponding core outcome measurement instruments (study 4). ETHICS AND DISSEMINATION: Studies 1 and 2 have been registered with the Australian and New Zealand Clinical Trial Registry (ACTRN12623001313628). Ethics approval has been obtained from the Royal Brisbane and Women\u27s Hospital (HREC/2023/MNHB/95293) and The University of Queensland (2022/HE001946 and 2023/HE001175). Study findings will be disseminated through peer-reviewed publications, conference presentations and engagement with relevant stakeholders including healthcare providers, policy-makers, stroke and rehabilitation audit and clinical quality registry custodians, consumer support organisations, and individuals with aphasia and their families

Safety, Immunogenicity and Efficacy of Prime-Boost Vaccination with ChAd63 and MVA Encoding ME-TRAP against Plasmodium falciparum Infection in Adults in Senegal.

Malaria transmission is in decline in some parts of Africa, partly due to the scaling up of control measures. If the goal of elimination is to be achieved, additional control measures including an effective and durable vaccine will be required. Studies utilising the prime-boost approach to deliver viral vectors encoding the pre-erythrocytic antigen ME-TRAP (multiple epitope thrombospondin-related adhesion protein) have shown promising safety, immunogenicity and efficacy in sporozoite challenge studies. More recently, a study in Kenyan adults, similar to that reported here, showed substantial efficacy against P. falciparum infection. One hundred and twenty healthy male volunteers, living in a malaria endemic area of Senegal were randomised to receive either the Chimpanzee adenovirus (ChAd63) ME-TRAP as prime vaccination, followed eight weeks later by modified vaccinia Ankara (MVA) also encoding ME-TRAP as booster, or two doses of anti-rabies vaccine as a comparator. Prior to follow-up, antimalarials were administered to clear parasitaemia and then participants were monitored by PCR for malaria infection for eight weeks. The primary endpoint was time-to-infection with P. falciparum malaria, determined by two consecutive positive PCR results. Secondary endpoints included adverse event reporting, measures of cellular and humoral immunogenicity and a meta-analysis of combined vaccine efficacy with the parallel study in Kenyan adults.We show that this pre-erythrocytic malaria vaccine is safe and induces significant immunogenicity, with a peak T-cell response at seven days after boosting of 932 Spot Forming Cells (SFC)/106 Peripheral Blood Mononuclear Cells(PBMC) compared to 57 SFC/ 106 PBMCs in the control group. However, a vaccine efficacy was not observed: 12 of 57 ME-TRAP vaccinees became PCR positive during the intensive monitoring period as compared to 13 of the 58 controls (P = 0.80). This trial confirms that vaccine efficacy against malaria infection in adults may be rapidly assessed using this efficient and cost-effective clinical trial design. Further efficacy evaluation of this vectored candidate vaccine approach in other malaria transmission settings and age-de-escalation into the main target age groups for a malaria vaccine is in progress

Proactive vaccination using multiviral Quartet Nanocages to elicit broad anti-coronavirus responses

Defending against future pandemics requires vaccine platforms that protect across a range of related pathogens. Nanoscale patterning can be used to address this issue. Here, we produce quartets of linked receptor-binding domains (RBDs) from a panel of SARS-like betacoronaviruses, coupled to a computationally designed nanocage through SpyTag/SpyCatcher links. These Quartet Nanocages, possessing a branched morphology, induce a high level of neutralizing antibodies against several different coronaviruses, including against viruses not represented in the vaccine. Equivalent antibody responses are raised to RBDs close to the nanocage or at the tips of the nanoparticle’s branches. In animals primed with SARS-CoV-2 Spike, boost immunizations with Quartet Nanocages increase the strength and breadth of an otherwise narrow immune response. A Quartet Nanocage including the Omicron XBB.1.5 ‘Kraken’ RBD induced antibodies with binding to a broad range of sarbecoviruses, as well as neutralizing activity against this variant of concern. Quartet nanocages are a nanomedicine approach with potential to confer heterotypic protection against emergent zoonotic pathogens and facilitate proactive pandemic protection

A horizon scan of issues affecting UK forest management within 50 years

Forests are in the spotlight: they are expected to play a pivotal role in our response to society’s greatest challenges, such as the climate and biodiversity crises. Yet, the forests themselves, and the sector that manages them, face a range of interrelated threats and opportunities. Many of these are well understood, even if the solutions remain elusive. However, there are also emerging trends that are currently less widely appreciated. We report here the results of a horizon scan to identify developing issues likely to affect UK forest management within the next 50 years. These are issues that are presently under-recognized but have potential for significant impact across the sector and beyond. As the forest management sector naturally operates over long timescales, the importance of using good foresight is self-evident. We followed a tried-and-tested horizon scanning methodology involving a diverse Expert Panel to collate and prioritize a longlist of 180 issues. The top 15 issues identified are presented in the Graphical Abstract. The issues represent a diverse range of themes, within a spectrum of influences from environmental shocks and perturbations to changing political and socio-economic drivers, with complex emerging interactions between them. The most highly ranked issue was ‘Catastrophic forest ecosystem collapse’, reflecting agreement that not only is such collapse a likely prospect but it would also have huge implications across the sector and wider society. These and many of the other issues are large scale, with far-reaching implications. We must be careful to avoid inaction through being overwhelmed, or indeed to merely focus on ‘easy wins’ without considering broader ramifications. Our responses to each of the challenges and opportunities highlighted must be synergistic and coherent, involving landscape-scale planning. A more adaptive approach to forest management will be essential, encouraging continual innovation and learning. The 15 horizon scan issues presented here are a starting point on which to build further research, prompt debate and action, and develop evidence-based policy and practice. We hope that this stimulates greater recognition of how our forests and sector may need to change to be fit for the future. In some cases, these changes will need to be fundamental and momentous

Around the hybrid conference world in the COVID-19 era

In-person and online conferences each have their benefits, with hybrid conferences intended to blend the best of both worlds. But do hybrid conferences fulfil the promise? Fifteen attendees across three global conferences share their collective experiences.Peer reviewe