Non-perturbative orientifold transitions at the conifold

After orientifold projection, the conifold singularity in hypermultiplet moduli space of Calabi-Yau compactifications cannot be avoided by geometric deformations. We study the non-perturbative fate of this singularity in a local model involving O6-planes and D6-branes wrapping the deformed conifold in Type IIA string theory. We classify possible A-type orientifolds of the deformed conifold and find that they cannot all be continued to the small resolution. When passing through the singularity on the deformed side, the O-plane charge generally jumps by the class of the vanishing cycle. To decide which classical configurations are dynamically connected, we construct the quantum moduli space by lifting the orientifold to M-theory as well as by looking at the superpotential. We find a rich pattern of smooth and phase transitions depending on the total sixbrane charge. Non-BPS states from branes wrapped on non-supersymmetric bolts are responsible for a phase transition. We also clarify the nature of a Z_2 valued D0-brane charge in the 6-brane background. Along the way, we obtain a new metric of G_2 holonomy corresponding to an O6-plane on the three sphere of the deformed conifold.Comment: 76 pages, references adde

Raised FGF23 Correlates to Increased Mortality in Critical Illness, Independent of Vitamin D

BACKGROUND: Fibroblast Growth Factor (FGF23) is an endocrine hormone classically associated with the homeostasis of vitamin D, phosphate, and calcium. Elevated serum FGF23 is a known independent risk factor for mortality in chronic kidney disease (CKD) patients. We aimed to determine if there was a similar relationship between FGF23 levels and mortality in critically ill patients.METHODS: Plasma FGF23 levels were measured by ELISA in two separate cohorts of patients receiving vitamin D supplementation: critical illness patients (VITdAL-ICU trial, n = 475) and elective oesophagectomy patients (VINDALOO trial, n = 76). Mortality data were recorded at 30 and 180 days or at two years, respectively. FGF23 levels in a healthy control cohort were also measured ( n = 27). RESULTS: Elevated FGF23 (quartile 4 vs. quartiles 1-3) was associated with increased short-term (30 and 180 day) mortality in critical illness patients ( p &lt; 0.001) and long-term (two-year) mortality in oesophagectomy patients ( p = 0.0149). Patients who died had significantly higher FGF23 levels than those who survived: In the critical illness cohort, those who died had 1194.6 pg/mL (range 0-14,000), while those who survived had 120.4 pg/mL (range = 15-14,000) ( p = 0.0462). In the oesophagectomy cohort, those who died had 1304 pg/mL (range = 154-77,800), while those who survived had 644 pg/mL (range = 179-54,894) ( p &lt; 0.001). This was found to be independent of vitamin D or CKD status (critical illness p = 0.3507; oesophagectomy p = 0.3800). FGF23 levels in healthy controls were similar to those seen in oesophagectomy patients ( p = 0.4802). CONCLUSIONS: Elevated baseline serum FGF23 is correlated with increased mortality in both the post-oesophagectomy cohort and the cohort of patients with critical illness requiring intensive care admission. This was independent of vitamin D status, supplementation, or CKD status, which suggests the presence of vitamin D-independent mechanisms of FGF23 action during the acute and convalescent stages of critical illness, warranting further investigation.</p

Vitamin D to prevent lung injury following esophagectomy: A randomized, placebo-controlled trial

Objectives: Observational studies suggest an association between vitamin D deficiency and adverse outcomes of critical illness and identify it as a potential risk factor for the development of lung injury. To determine whether pre-operative administration of oral high-dose cholecalciferol ameliorates early acute lung injury post-operatively in adults undergoing elective esophagectomy. Design: A double-blind, randomized, placebo-controlled trial. Setting: Three large UK university hospitals. Patients: Seventy-nine adult patients undergoing elective esophagectomy were randomized. Intervention: A single oral preoperative (3-14 days) dose of 7.5mg (300,000IU; 15mls) cholecalciferol or matched placebo. Measurements and Main Results: Primary outcome was change in extravascular lung water index (EVLWI) at the end of esophagectomy. Secondary outcomes included PaO2:FiO2 ratio, development of lung injury, ventilator and organ-failure free days, 28 and 90 day survival, safety of cholecalciferol supplementation, plasma vitamin D status (25(OH)D, 1,25(OH)2D and vitamin D binding protein), pulmonary vascular permeability index (PVPI) and EVLWI day 1 postoperatively. An exploratory study measured biomarkers of alveolar-capillary inflammation and injury. Forty patients were randomized to cholecalciferol and 39 to placebo. There was no significant change in EVLWI at the end of the operation between treatment groups (placebo median 1.0[IQR 0.4 – 1.8] vs cholecalciferol median 0.4[IQR 0.4 – 1.2] ml/kg, p=0.059). Median PVPI values were significantly lower in the cholecalciferol treatment group (placebo 0.4[IQR 0 – 0.7] vs cholecalciferol 0.1[IQR -0.15 -0.35], p=0.027). Cholecalciferol treatment effectively increased 25(OH)D concentrations but surgery resulted in a decrease in 25(OH)D concentrations at day 3 in both arms. There was no difference in clinical outcomes. Conclusions: High-dose preoperative treatment with oral cholecalciferol was effective at increasing 25(OH)D concentrations, and reduced changes in postoperative PVPI but not EVLWI

Variation in hospital cleaning practice and process in Australian hospitals: A structured mapping exercise

BackgroundThe purpose of this paper is to highlight the range of cleaning practices and processes in 11 Australian hospitals and to discuss the challenges this variation poses to the implementation of clinical trials or changes to hospital cleaning practices.MethodsA cross-sectional study design was used to determine cleaning practices and processes in hospitals participating in the ‘Researching Effective Approaches to Cleaning in Hospitals’ (REACH) study. A standardised template and approach was used to collect information. Data collection activities included structured on-site discussions, a review of hospital practices and a document review of policy and procedural documents related to cleaning.ResultsVariations in the auditing process used to evaluate environmental cleanliness, cleaning practices, product use, training and communication pathways available to cleaning staff were identified. There was also variation in workforce structure and responsibilities for cleaning.ConclusionThis paper is the first to describe the differences in cleaning practices between Australian hospitals. The variations identified present a number of challenges for the conduct of research and have important implications for both monitoring of and standards for cleanliness. These challenges include implementing a practice change or cleaning study where hospitals have different processes, practices and structure

Researching effective approaches to cleaning in hospitals: protocol of the REACH study, a multi-site stepped-wedge randomised trial

BackgroundThe Researching Effective Approaches to Cleaning in Hospitals (REACH) study will generate evidence about the effectiveness and cost-effectiveness of a novel cleaning initiative that aims to improve the environmental cleanliness of hospitals. The initiative is an environmental cleaning bundle, with five interdependent, evidence-based components (training, technique, product, audit and communication) implemented with environmental services staff to enhance hospital cleaning practices.Methods/designThe REACH study will use a stepped-wedge randomised controlled design to test the study intervention, an environmental cleaning bundle, in 11 Australian hospitals. All trial hospitals will receive the intervention and act as their own control, with analysis undertaken of the change within each hospital based on data collected in the control and intervention periods. Each site will be randomised to one of the 11 intervention timings with staggered commencement dates in 2016 and an intervention period between 20 and 50 weeks. All sites complete the trial at the same time in 2017. The inclusion criteria allow for a purposive sample of both public and private hospitals that have higher-risk patient populations for healthcare-associated infections (HAIs). The primary outcome (objective one) is the monthly number of Staphylococcus aureus bacteraemias (SABs), Clostridium difficile infections (CDIs) and vancomycin resistant enterococci (VRE) infections, per 10,000 bed days. Secondary outcomes for objective one include the thoroughness of hospital cleaning assessed using fluorescent marker technology, the bio-burden of frequent touch surfaces post cleaning and changes in staff knowledge and attitudes about environmental cleaning. A cost-effectiveness analysis will determine the second key outcome (objective two): the incremental cost-effectiveness ratio from implementation of the cleaning bundle.The study uses the integrated Promoting Action on Research Implementation in Health Services (iPARIHS) framework to support the tailored implementation of the environmental cleaning bundle in each hospital.DiscussionEvidence from the REACH trial will contribute to future policy and practice guidelines about hospital environmental cleaning. It will be used by healthcare leaders and clinicians to inform decision-making and implementation of best-practice infection prevention strategies to reduce HAIs in hospitals

What were the historical reasons for the resistance to recognizing airborne transmission during the COVID‐19 pandemic?

The question of whether SARS‐CoV‐2 is mainly transmitted by droplets or aerosols has been highly controversial. We sought to explain this controversy through a historical analysis of transmission research in other diseases. For most of human history, the dominant paradigm was that many diseases were carried by the air, often over long distances and in a phantasmagorical way. This miasmatic paradigm was challenged in the mid to late 19th century with the rise of germ theory, and as diseases such as cholera, puerperal fever, and malaria were found to actually transmit in other ways. Motivated by his views on the importance of contact/droplet infection, and the resistance he encountered from the remaining influence of miasma theory, prominent public health official Charles Chapin in 1910 helped initiate a successful paradigm shift, deeming airborne transmission most unlikely. This new paradigm became dominant. However, the lack of understanding of aerosols led to systematic errors in the interpretation of research evidence on transmission pathways. For the next five decades, airborne transmission was considered of negligible or minor importance for all major respiratory diseases, until a demonstration of airborne transmission of tuberculosis (which had been mistakenly thought to be transmitted by droplets) in 1962. The contact/droplet paradigm remained dominant, and only a few diseases were widely accepted as airborne before COVID‐19: those that were clearly transmitted to people not in the same room. The acceleration of interdisciplinary research inspired by the COVID‐19 pandemic has shown that airborne transmission is a major mode of transmission for this disease, and is likely to be significant for many respiratory infectious diseases