Two-way communication with neural networks in vivo using focused light

Neuronal networks process information in a distributed, spatially heterogeneous manner that transcends the layout of electrodes. In contrast, directed and steerable light offers the potential to engage specific cells on demand. We present a unified framework for adapting microscopes to use light for simultaneous in vivo stimulation and recording of cells at fine spatiotemporal resolutions. We use straightforward optics to lock onto networks in vivo, to steer light to activate circuit elements and to simultaneously record from other cells. We then actualize this 'free' augmentation on both an 'open' two-photon microscope and a leading commercial one. By following this protocol, setup of the system takes a few days, and the result is a noninvasive interface to brain dynamics based on directed light, at a network resolution that was not previously possible and which will further improve with the rapid advance in development of optical reporters and effectors. This protocol is for physiologists who are competent with computers and wish to extend hardware and software to interface more fluidly with neuronal networks.National Institutes of Health (U.S.) (Postdoctoral Fellowship)Simons Foundation (Postdoctoral Fellowship)National Institutes of Health (U.S.) (Predoctoral Fellowship)National Institutes of Health (U.S.)Simons Foundatio

The future of resilient supply chains

While supply chain resilience has been touched upon frequently, research remains (with the exception of often repeated anecdotal examples) relatively disparate on what disruptions actually are. This research aims to advance theoretical and managerial understandings around the management of supply chain disruptions. A two-stage research process is used which focuses first on polling academic experts. This stage is followed by the extraction of insights from practitioners in the automotive, electronics and food industries. Our findings coalesce around: (1) the types of disruptions that respondents are most concerned about; (2) the associated strategies suggested to cope with disruptions; and, (3) how resilience can be measured. It is apparent that there are some areas where academics and practitioners agree and others where they agree to a lesser extent. Both sets of actors tend to agree on how resilience can be quantified, with recovery time the preferred indicator. However, there is a discrepancy around how resilience is achieved within the supply chain. Academics emphasise the importance of redundancy while practitioners refer more to flexibility. Also, they disagree around what constitutes “key disruptions”: academics suggested high-profile events, while practitioners are more concerned with day-to-day problems

Variation of Basal EROD Activities in Ten Passerine Bird Species – Relationships with Diet and Migration Status

Inter-specific differences in animal defence mechanisms against toxic substances are currently poorly understood. The ethoxyresorufin-O-deethylase (EROD) enzyme plays an important role in defence against toxic chemicals in a wide variety of animals, and it is an important biomarker for environmental contamination. We compared basal hepatic EROD activity levels among ten passerine species to see if there is inter-specific variation in enzyme activity, especially in relation to their diet and migration status. Migratory insectivores showed higher EROD activity compared to granivores. We hypothesize that the variable invertebrate diet of migratory insectivores contains a wider range of natural toxins than the narrower diet of granivores. This may have affected the evolution of mixed function oxidases (MFO) system and enzyme activities. We further tested whether metabolic rates or relative liver size were associated with the variation in detoxification capacity. We found no association between EROD activity and relative (per mass unit) basal metabolic rate (BMR). Instead, EROD activity and relative liver mass (% of body mass) correlated positively, suggesting that a proportionally large liver also functions efficiently. Our results suggest that granivores and non-migratory birds may be more vulnerable to environmental contaminants than insectivores and migratory birds. The diet and migration status, however, are phylogenetically strongly connected to each other, and their roles cannot be fully separated in our analysis with only ten passerine species

Clostridium difficile infection.

Infection of the colon with the Gram-positive bacterium Clostridium difficile is potentially life threatening, especially in elderly people and in patients who have dysbiosis of the gut microbiota following antimicrobial drug exposure. C. difficile is the leading cause of health-care-associated infective diarrhoea. The life cycle of C. difficile is influenced by antimicrobial agents, the host immune system, and the host microbiota and its associated metabolites. The primary mediators of inflammation in C. difficile infection (CDI) are large clostridial toxins, toxin A (TcdA) and toxin B (TcdB), and, in some bacterial strains, the binary toxin CDT. The toxins trigger a complex cascade of host cellular responses to cause diarrhoea, inflammation and tissue necrosis - the major symptoms of CDI. The factors responsible for the epidemic of some C. difficile strains are poorly understood. Recurrent infections are common and can be debilitating. Toxin detection for diagnosis is important for accurate epidemiological study, and for optimal management and prevention strategies. Infections are commonly treated with specific antimicrobial agents, but faecal microbiota transplants have shown promise for recurrent infections. Future biotherapies for C. difficile infections are likely to involve defined combinations of key gut microbiota

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Ambient air pollution and thrombosis

Abstract Air pollution is a growing public health concern of global significance. Acute and chronic exposure is known to impair cardiovascular function, exacerbate disease and increase cardiovascular mortality. Several plausible biological mechanisms have been proposed for these associations, however, at present, the pathways are incomplete. A seminal review by the American Heart Association (2010) concluded that the thrombotic effects of particulate air pollution likely contributed to their effects on cardiovascular mortality and morbidity. The aim of the current review is to appraise the newly accumulated scientific evidence (2009–2016) on contribution of haemostasis and thrombosis towards cardiovascular disease induced by exposure to both particulate and gaseous pollutants. Seventy four publications were reviewed in-depth. The weight of evidence suggests that acute exposure to fine particulate matter (PM2.5) induces a shift in the haemostatic balance towards a pro-thrombotic/pro-coagulative state. Insufficient data was available to ascertain if a similar relationship exists for gaseous pollutants, and very few studies have addressed long-term exposure to ambient air pollution. Platelet activation, oxidative stress, interplay between interleukin-6 and tissue factor, all appear to be potentially important mechanisms in pollution-mediated thrombosis, together with an emerging role for circulating microvesicles and epigenetic changes. Overall, the recent literature supports, and arguably strengthens, the contention that air pollution contributes to cardiovascular morbidity by promoting haemostasis. The volume and diversity of the evidence highlights the complexity of the pathophysiologic mechanisms by which air pollution promotes thrombosis; multiple pathways are plausible and it is most likely they act in concert. Future research should address the role gaseous pollutants play in the cardiovascular effects of air pollution mixture and direct comparison of potentially susceptible groups to healthy individuals

The impact of age and severity of comorbid illness on outcomes after isolated aortic valve replacement for aortic stenosis

Mark J Russo,1,2 Alexander Iribarne,3 Emily Chen,2 Ashwin Karanam,2 Chris Pettit,2 Fabio Barili,4 Atman P Shah,5 Craig R Saunders1,2 1Barnabas Health Hospital, Newark/Livingston, NJ, USA; 2Barnabas Health Cardiovascular Clinical Research Center, Newark, NJ, USA; 3Duke University, Durham, NC, USA; 4Department of Cardiovascular Surgery, S Croce Hospital, Cuneo, Italy; 5University of Chicago, Chicago, IL, USA Objectives: This study examines outcomes in a national sample of patients undergoing isolated aortic valve replacement (AVR) for aortic stenosis, with particular focus on advanced-age patients and those with extreme severity of comorbid illness (SOI). Methods: Data were obtained from the Nationwide Inpatient Sample and included all patients undergoing AVRs performed from January 1, 2006 to December 31, 2008. Patients with major concomitant cardiac procedures, as well as those aged &lt;20 years, and those with infective endocarditis or aortic insufficiency without aortic stenosis, were excluded from analysis. The analysis included 13,497 patients. Patients were stratified by age and further stratified by All Patient Refined Diagnosis Related Group SOI into mild/moderate, major, and extreme subgroups. Results: Overall in-hospital mortality was 2.96% (n=399); in-hospital mortality for the &ge;80-year-old group (n=139, 4.78%) was significantly higher than the 20- to 49-year-old (n=9, 0.84%, P&lt;0.001) or 50- to 79-year-old (n=251, 2.64%, P&lt;0.001) groups. In-hospital mortality was significantly higher in the extreme SOI group (n=296, 15.33%) than in the minor/moderate (n=22, 0.35%, P&lt;0.001) and major SOI groups (n=81, 1.51%, P&lt;0.001). Median in-hospital costs in the mild/moderate, major, and extreme SOI strata were $29,202.08,$36,035.13, and $57,572.92, respectively. Conclusion: In the minor, moderate, and major SOI groups, in-hospital mortality and costs are low regardless of age; these groups represent &gt;85% of patients undergoing isolated AVR for aortic stenosis. Conversely, in patients classified as having extreme SOI, surgical therapy is associated with exceedingly high inpatient mortality, low home discharge rates, and high resource utilization, particularly in the advanced age group. Keywords: cardiac surgery, outcomes, risk stratification&nbsp