Killing without collateral damage: new hope for sepsis therapy.

Dr Proudfoot is a Wellcome Trust Clinical Research Training Fellow and Dr Summers is a Wellcome Trust Postdoctoral Clinical Training Fellow.This is the accepted manuscript version. The final version is available from NPG at http://www.nature.com/icb/journal/v92/n9/full/icb201473a.html

Major surgery and the immune system: from pathophysiology to treatment.

PURPOSE OF REVIEW: The purpose of this review is to provide an overview of the immune response to major surgery, and the ways in which it may be modulated to improve postoperative outcomes. RECENT FINDINGS: Data from patients who have undergone a variety of tissue injuries (surgery, burns, sepsis, trauma) have shown the presence of a conserved 'genomic storm' that alters the leukocyte transcriptome, with upregulation of the innate immune response and concomitant downregulation of the adaptive immune response. The innate and adaptive immune systems are often regarded largely distinct. However, more recent evidence suggests there are critical connections between the two arms of the immune response, whereby innate immune cells are able to suppress the adaptive response. SUMMARY: The immune system is critical to the host response to tissue injury occurring due to surgery. However, the physiological processes required to resolve the surgical insult can also contribute to sequelae such as cognitive decline, pneumonia and acute kidney injury. Our understanding of the immune pathogenesis underlying these complications is improving, leading to interest in the development of immunomodulatory therapies, which aim to permit host defence whilst ameliorating postoperative complications

Examining the effects of magnetic fields in neutron star mergers through numerical simulations

In this thesis, we present simulations of merging binary neutron stars, carried out using the publicly available FLASH code framework. These are 3D Newtonian magnetohydrodynamic simulations, in which we have included gravitational wave effects through the use of a source term. We trial different implementations of this source term and discuss the results. We then use this model to investigate the role of magnetic fields in binary neutron star mergers. We endow each neutron star with a dipolar magnetic field and examine how the orientation of the dipole affects the strength and structure of the magnetic field during the merger. This has important implications for the ability of the merger remnant to produce a short gamma ray burst jet. In a second project, we simulate a magnetized accretion torus surrounding a black hole. We implement a model black hole in the FLASH code framework using a Pseudo-Newtonian potential to reproduce features, such as the innermost stable circular orbit, which are important to accretion disc studies. We compare the results of our magnetized accretion disc simulations with similar studies, finding broad agreement with accretion rates and the general structure of the magnetic field

Mathematical modeling supports the presence of neutrophil depriming in vivo.

Abstract Following migration into the intestinal mucosa in inflammatory bowel disease (IBD), neutrophils enter the intestinal lumen and are excreted. This provides a basis for quantification of disease activity by measuring excreted label following injection of In-111-labeled neutrophils. In severe pan-colitis, 50% of the injected In-111 is typically recovered in the feces, indicating that 50% of neutrophil turnover is via fecal excretion. Neutrophils have an intravascular lifespan of ~10 h and a distribution volume of ~10 L, so total body neutrophil turnover is 10.N/10 cells/h, where N is the peripheral blood neutrophil count (cells/L). Neutrophil loss via the colon in a patient with 50% fecal In-111 loss is therefore N/120 cells/min. Pan-colonic mucosal-blood flow in pan-colitis is 200 mL/min, which would deliver N/5 neutrophils to the colon per min. Therefore, 5/120, or 4%, of incoming neutrophils undergo migration into inflamed bowel. If the 96% of nonmigrating cells exit in a primed state, then at steady state >90% of circulating neutrophils would be primed if no depriming took place. As the highest level of priming seen in IBD is ~40%, this indicates that depriming within the circulation must take place. Using the above values in the steady state equation relating priming rate to depriming rate plus primed-cell destruction rate gives a mean depriming time of 35 min. We conclude that a very small proportion of neutrophils entering a site of inflammation migrate and that in vivo depriming must take place to limit the numbers of primed neutrophils in the circulation.This study was supported by the Wellcome Trust and the UK‐US Fulbright Commission; CS holds a Wellcome Trust Postdoctoral Clinical Research Fellowship and a Fulbright Scholar award. The work in the Chilvers lab is funded by the Wellcome Trust, MRC, Asthma‐UK, BBSRC, Gates Foundation and NIHR Cambridge BRC.This is the final published version, also available from http://physreports.physiology.org/content/2/3/e00241.long

Supervised machine learning for the early prediction of acute respiratory distress syndrome (ARDS).

PURPOSE: Acute respiratory distress syndrome (ARDS) is a serious respiratory condition with high mortality and associated morbidity. The objective of this study is to develop and evaluate a novel application of gradient boosted tree models trained on patient health record data for the early prediction of ARDS. MATERIALS AND METHODS: 9919 patient encounters were retrospectively analyzed from the Medical Information Mart for Intensive Care III (MIMIC-III) data base. XGBoost gradient boosted tree models for early ARDS prediction were created using routinely collected clinical variables and numerical representations of radiology reports as inputs. XGBoost models were iteratively trained and validated using 10-fold cross validation. RESULTS: On a hold-out test set, algorithm classifiers attained area under the receiver operating characteristic curve (AUROC) values of 0.905 when tested for the detection of ARDS at onset and 0.827, 0.810, and 0.790 for the prediction of ARDS at 12-, 24-, and 48-h windows prior to onset, respectively. CONCLUSION: Supervised machine learning predictions may help predict patients with ARDS up to 48 h prior to onset

Understanding the security and privacy concerns about the use of identifiable health data in the context of the COVID-19 pandemic : survey study of public attitudes toward COVID-19 and data-sharing

Background: The COVID-19 pandemic increased the availability and use of population and individual health data to optimize tracking and analysis of the spread of the virus. Many health care services have had to rapidly digitalize in order to maintain the continuity of care provision. Data collection and dissemination have provided critical support for defending against the spread of the virus since the beginning of the pandemic; however, little is known about public perceptions of and attitudes toward the use, privacy, and security of data. Objective: The goal of this study is to better understand people’s willingness to share data in the context of the COVID-19 pandemic. Methods: A web-based survey was conducted on individuals’ use of and attitudes toward health data for individuals aged 18 years and older, and in particular, with a reported diagnosis of a chronic health condition placing them at the highest risk of severe COVID-19. Results: In total, 4764 individuals responded to this web-based survey, of whom 4674 (98.1%) reported a medical diagnosis of at least 1 health condition (3 per person on average), with type 2 diabetes (n=2974, 62.7%), hypertension (n=2147, 45.2%), and type 1 diabetes (n=1299, 27.4%) being most prominent in our sample. In general, more people are comfortable with sharing anonymized data than personally identifiable data. People reported feeling comfortable sharing data that were able to benefit others; 66% (3121 respondents) would share personal identifiable data if its primary purpose was deemed beneficial for the health of others. Almost two-thirds (n=3026; 63.9%) would consent to sharing personal, sensitive health data with government or health authority organizations. Conversely, over a quarter of respondents (n=1297, 27.8%) stated that they did not trust any organization to protect their data, and 54% (n=2528) of them reported concerns about the implications of sharing personal information. Almost two-thirds (n=3054, 65%) of respondents were concerned about the provisions of appropriate legislation that seeks to prevent data misuse and hold organizations accountable in the case of data misuse. Conclusions: Although our survey focused mainly on the views of those living with chronic health conditions, the results indicate that data sensitivity is highly contextual. More people are more comfortable with sharing anonymized data rather than personally identifiable data. Willingness to share data also depended on the receiving body, highlighting trust as a key theme, in particular who may have access to shared personal health data and how they may be used in the future. The nascency of legal guidance in this area suggests a need for humanitarian guidelines for data responsibility during disaster relief operations such as pandemics and for involving the public in their development

The low carb program for people with type 2 diabetes and pre-diabetes - a mixed methods feasibility study of signposting from general practice

Background: Evidence shows type 2 diabetes mellitus (T2DM) can be effectively treated with a reduced-carbohydrate diet to support weight loss. Digital apps are increasingly used to support weight loss, yet little is known about their use as part of general practice diabetes care. Aim: Determine the feasibility of signposting from routine NHS general practice to a digital weight management tool (Low Carb Program) for patients with T2DM and pre-diabetes. Design & setting: Mixed-methods feasibility study implemented within routine general practice consultations at four practices in the Midlands, England. Method: General practices offered signposting to eligible patients attending consultations of any type during a 4-week recruitment period. Rates of offering and accepting signposting were recorded, with program registration, program completion, and self-reported health outcomes (weight, haemoglobin A1C [HbA1c]). Results: Signposting was offered to 351 patients; 160 (45.6%) accepted, 103 (29.3%) registered with the intervention and 43 (26.9% of patients accepting signposting) completed the programme. GPs reported that signposting added between 1–4 minutes to the consultation length. Patients completing the programme reported greater weight loss (7.2kg versus 1.6kg, P<0.001) and HbA1c improvements (-9.1mmol/mol versus 1.7mmol/mol, P<0.001) compared to those who did not, and were more likely to reduce the number of prescribed diabetes medications in general practice. Conclusions: Signposting from real-world general practice to the Low Carb Program is feasible and can potentially improve diabetes outcomes. Further research should explore whether the process of signposting can be enhanced to increase registration, identify whether additional practice-led support leads to increased programme completion, and confirm the intervention’s clinical and cost-effectiveness

Alumnae Association Bulletin of the School of Nursing, 1972

Alumnae Calendar The President\u27s Message Officers and Chairmen of Committees Financial Report Address by President Herbut School of Nursing Report School of Practical Nursing Report Report by Dr. Mary Louise Soentgen, M.D., F.A.A.P. Report of Patient Services Department Report of Staff Nurses\u27 Association Progress Report of Hospital Activities Scholarship Committee Report - Clerk-Typist Annual Luncheon - Head Table Social Events for 1971-1972 Missing Alumnae Members Jefferson Today Ways and Means Committee Report Constitution and By-Laws Report Sick and Welfare Committee Women\u27s Board Report Baccalaureate Degree Program Luncheon Pictures Resume of Minutes of Alumnae Association Meeting Class News Poem by Rosa Diseroad - 1923 Marriages Births - Hello World In Memoriam Notice

Investigating interfacial electron transfer in dye-sensitized NiO using vibrational spectroscopy

Understanding what influences the formation and lifetime of charge-separated states is key to developing photoelectrochemical devices. This paper describes the use of time-resolved infrared absorption spectroscopy (TRIR) to determine the structure and lifetime of the intermediates formed on photoexcitation of two organic donor–π–acceptor dyes adsorbed to the surface of NiO. The donor and π-linker of both dyes is triphenylamine and thiophene but the acceptors differ, maleonitrile (1) and bodipy (2). Despite their structural similarities, dye 1 outperforms 2 significantly in devices. Strong transient bands in the fingerprint region (1 and 2) and nitrile region (2300–2000 cm−1) for 1 enabled us to monitor the structure of the excited states in solution or adsorbed on NiO (in the absence and presence of electrolyte) and the corresponding kinetics, which are on a ps–ns timescale. The results are consistent with rapid (<1 ps) charge-transfer from NiO to the excited dye (1) to give exclusively the charge-separated state on the timescale of our measurements. Conversely, the TRIR experiments revealed that multiple species are present shortly after excitation of the bodipy chromophore in 2, which is electronically decoupled from the thiophene linker. In solution, excitation first populates the bodipy singlet excited state, followed by charge transfer from the triphenylamine to the bodipy. The presence and short lifetime (τ ≈ 30 ps) of the charge-transfer excited state when 2 is adsorbed on NiO (2|NiO) suggests that charge separation is slower and/or less efficient in 2|NiO than in 1|NiO. This is consistent with the difference in performance between the two dyes in dye-sensitized solar cells and photoelectrochemical water splitting devices. Compared to n-type materials such as TiO2, less is understood regarding electron transfer between dyes and p-type metal oxides such as NiO, but it is evident that fast charge-recombination presents a limit to the performance of photocathodes. This is also a major challenge to photocatalytic systems based on a “Z-scheme”, where the catalysis takes place on a µs–s timescale