Genetic relatedness of infecting and reinfecting respiratory syncytial virus strains identified in a birth cohort from rural Kenya

Background: Respiratory syncytial virus (RSV) reinfects individuals repeatedly. The extent to which this is a consequence of RSV antigenic diversity is unclear. Methods: Six-hundred thirty-five children from rural Kenya were closely monitored for RSV infection from birth through 3 consecutive RSV epidemics. RSV infections were identified by immunofluorescence testing of nasal washing samples collected during acute respiratory illnesses, typed into group A and B, and sequenced in the attachment (G) protein. A positive sample separated from a previous positive by ≥14 days was defined as a reinfection a priori. Results: Phylogenetic analysis was undertaken for 325 (80%) of 409 identified infections, including 53 (64%) of 83 reinfections. Heterologous group reinfections were observed in 28 episodes, and homologous group reinfections were observed in 25 episodes; 10 involved homologous genotypes, 5 showed no amino acid changes, and 3 were separated by 21–24 days and were potentially persistent infections. The temporal distribution of genotypes among reinfections did not differ from that of single infections. Conclusions: The vast majority of infection and reinfection pairs differed by group, genotype, or G amino acid sequence (ie, comprised distinct viruses). The extent to which this is a consequence of immune memory of infection history or prevalent diversity remains unclear

Indoor robot gardening: design and implementation

This paper describes the architecture and implementation of a distributed autonomous gardening system with applications in urban/indoor precision agriculture. The garden is a mesh network of robots and plants. The gardening robots are mobile manipulators with an eye-in-hand camera. They are capable of locating plants in the garden, watering them, and locating and grasping fruit. The plants are potted cherry tomatoes enhanced with sensors and computation to monitor their well-being (e.g. soil humidity, state of fruits) and with networking to communicate servicing requests to the robots. By embedding sensing, computation, and communication into the pots, task allocation in the system is de-centrally coordinated, which makes the system scalable and robust against the failure of a centralized agent. We describe the architecture of this system and present experimental results for navigation, object recognition, and manipulation as well as challenges that lie ahead toward autonomous precision agriculture with multi-robot teams.Swiss National Science Foundation (contract number PBEL2118737)United States. Army Research Office. Multidisciplinary University Research Initiative (MURI SWARMS project W911NF-05-1-0219)National Science Foundation (U.S.) (NSF IIS-0426838)Intel Corporation (EFRI 0735953 Intel)Massachusetts Institute of Technology (UROP program)Massachusetts Institute of Technology (MSRP program

Derivation and Validation of a Chronic Total Coronary Occlusion Intervention Procedural Success Score From the 20,000-Patient EuroCTO Registry: The EuroCTO (CASTLE) Score.

OBJECTIVES: The aim was to establish a contemporary scoring system to predict the outcome of chronic total occlusion coronary angioplasty. BACKGROUND: Interventional treatment of chronic total coronary occlusions (CTOs) is a developing subspecialty. Predictors of technical success or failure have been derived from datasets of modest size. A robust scoring tool could facilitate case selection and inform decision making. METHODS: The study analyzed data from the EuroCTO registry. This prospective database was set up in 2008 and includes >20,000 cases submitted by CTO expert operators (>50 cases/year). Derivation (n = 14,882) and validation (n = 5,745) datasets were created to develop a risk score for predicting technical failure. RESULTS: There were 14,882 patients in the derivation dataset (with 2,356 [15.5%] failures) and 5,745 in the validation dataset (with 703 [12.2%] failures). A total of 20.2% of cases were done retrogradely, and dissection re-entry was performed in 9.3% of cases. We identified 6 predictors of technical failure, collectively forming the CASTLE score (Coronary artery bypass graft history, Age (≥70 years), Stump anatomy [blunt or invisible], Tortuosity degree [severe or unseen], Length of occlusion [≥20 mm], and Extent of calcification [severe]). When each parameter was assigned a value of 1, technical failure was seen to increase from 8% with a CASTLE score of 0 to 1, to 35% with a score ≥4. The area under the curve (AUC) was similar in both the derivation (AUC: 0.66) and validation (AUC: 0.68) datasets. CONCLUSIONS: The EuroCTO (CASTLE) score is derived from the largest database of CTO cases to date and offers a useful tool for predicting procedural outcome

Some behavioral aspects of energy descent: How a biophysical psychology might help people transition through the lean times ahead

This article is part of the Research Topic: Nature and environment: The psychology of its benefits and its protection.We may soon face biophysical limits to perpetual growth. Energy supplies may tighten and then begin a long slow descent while defensive expenditures rise to address problems caused by past resource consumption. The outcome may be significant changes in daily routines at the individual and community level. It is difficult to know when this scenario might begin to unfold but it clearly would constitute a new behavioral context, one that the behavioral sciences least attends to. Even if one posits a less dramatic scenario, people may still need to make many urgent and perhaps unsettling transitions. And while a robust response would be needed, it is not at all clear what should be the details of that response. Since it is likely that no single response will fix things everywhere, for all people or for all time, it would be useful to conduct many social experiments. Indeed, a culture of small experiments should be fostered which, at the individual and small group level, can be described as behavioral entrepreneurship. This may have begun, hidden in plain sight, but more social experiments are needed. To be of help, it may be useful to both package behavioral insights in a way that is practitioner-oriented and grounded in biophysical trends and to propose a few key questions that need attention. This paper begins the process of developing a biophysical psychology, incomplete as it is at this early stage.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109261/1/De Young, R. (2014) Some behavioral aspects of energy descent, How a biophysical psychology might help people transition through the lean times ahead, Frontiers in Psychology, 5, 1255.pdfDescription of De Young, R. (2014) Some behavioral aspects of energy descent, How a biophysical psychology might help people transition through the lean times ahead, Frontiers in Psychology, 5, 1255.pdf : Main articl

Fractionation of Li, Be, Ga, Nb, Ta, In, Sn, Sb, W and Bi in the peraluminous Early Permian Variscan granites of the Cornubian Batholith: precursor processes to magmatic-hydrothermal mineralisation

The Early Permian Variscan Cornubian Batholith is a peraluminous, composite pluton intruded into Devonian and Carboniferous metamorphosed sedimentary and volcanic rocks. Within the batholith there are: G1 (two-mica), G2 (muscovite), G3 (biotite), G4 (tourmaline) and G5 (topaz) granites. G1-G2 and G3-G4 are derived from greywacke sources and linked through fractionation of assemblages dominated by feldspars and biotite, with minor mantle involvement in G3. G5 formed though flux-induced biotite-dominate melting in the lower crust during granulite facies metamorphism. Fractionation enriched G2 granites in Li (average 315 ppm), Be (12 ppm), Ta (4.4 ppm), In (74 ppb), Sn (18 ppm) and W (12 ppm) relative to crustal abundances and G1 granites. Gallium (24 ppm), Nb (16 ppm) and Bi (0.46 ppm) are not significantly enriched during fractionation, implying they are more compatible in the fractionating assemblage. Sb (0.16 ppm) is depleted in G1-G2 relative to the average upper and lower continental crust. Muscovite, a late-stage magmatic/subsolidus mineral, is the major host of Li, Nb, In, Sn and W in G2 granites. G2 granites are spatially associated with W-Sn greisen mineralisation. Fractionation within the younger G3-G4 granite system enriched Li (average 364 ppm), Ga (28 ppm), In (80 ppb), Sn (14 ppm), Nb (27 ppm), Ta (4.6 ppm), W (6.3 ppm) and Bi (0.61 ppm) in the G4 granites with retention of Be in G3 granites due to partitioning of Be into cordierite during fractionation. The distribution of Nb and Ta is controlled by accessory phases such as rutile within the G4 granites, facilitated by high F and lowering the melt temperature, leading to disseminated Nb and Ta mineralisation. Lithium, In, Sn and W are hosted in biotite micas which may prove favourable for breakdown on ingress of hydrothermal fluids. Higher degrees of scattering on trace element plots may be attributable to fluid–rock interactions or variability within the magma chamber. The G3-G4 system is more boron-rich, evidenced by a higher modal abundance of tourmaline. In this system, there is a stronger increase of Sn compared to G1-G2 granites, implying Sn in tourmaline-dominated mineral lodes may represent exsolution from G4 granites. G1-G4 granite abundances can be accounted for by 20–30% partial melting and 10–40% fractionation of a greywacke source. G5 granites are analogues of Rare Metal Granites described in France and Germany. These granites are enriched in Li (average 1363 ppm), Ga (38 ppm), Sn (21 ppm), W (24 ppm), Nb (52 ppm) and Ta (15 ppm). Within G5 granites, the metals partition into accessory minerals such as rutile, columbite-tantalite and cassiterite, forming disseminated magmatic mineralisation. High observed concentrations of Li, In, Sn, W, Nb and Ta in G4 and G5 granites are likely facilitated by high F, Li and P, which lower melt temperature and promote retention of these elements in the melt, prior to crystallisation of disseminated magmatic mineralisation

Binary systems and their nuclear explosions

Peer ReviewedPreprin

BHPR research: qualitative1. Complex reasoning determines patients' perception of outcome following foot surgery in rheumatoid arhtritis

Background: Foot surgery is common in patients with RA but research into surgical outcomes is limited and conceptually flawed as current outcome measures lack face validity: to date no one has asked patients what is important to them. This study aimed to determine which factors are important to patients when evaluating the success of foot surgery in RA Methods: Semi structured interviews of RA patients who had undergone foot surgery were conducted and transcribed verbatim. Thematic analysis of interviews was conducted to explore issues that were important to patients. Results: 11 RA patients (9 ♂, mean age 59, dis dur = 22yrs, mean of 3 yrs post op) with mixed experiences of foot surgery were interviewed. Patients interpreted outcome in respect to a multitude of factors, frequently positive change in one aspect contrasted with negative opinions about another. Overall, four major themes emerged. Function: Functional ability & participation in valued activities were very important to patients. Walking ability was a key concern but patients interpreted levels of activity in light of other aspects of their disease, reflecting on change in functional ability more than overall level. Positive feelings of improved mobility were often moderated by negative self perception ("I mean, I still walk like a waddling duck”). Appearance: Appearance was important to almost all patients but perhaps the most complex theme of all. Physical appearance, foot shape, and footwear were closely interlinked, yet patients saw these as distinct separate concepts. Patients need to legitimize these feelings was clear and they frequently entered into a defensive repertoire ("it's not cosmetic surgery; it's something that's more important than that, you know?”). Clinician opinion: Surgeons' post operative evaluation of the procedure was very influential. The impact of this appraisal continued to affect patients' lasting impression irrespective of how the outcome compared to their initial goals ("when he'd done it ... he said that hasn't worked as good as he'd wanted to ... but the pain has gone”). Pain: Whilst pain was important to almost all patients, it appeared to be less important than the other themes. Pain was predominately raised when it influenced other themes, such as function; many still felt the need to legitimize their foot pain in order for health professionals to take it seriously ("in the end I went to my GP because it had happened a few times and I went to an orthopaedic surgeon who was quite dismissive of it, it was like what are you complaining about”). Conclusions: Patients interpret the outcome of foot surgery using a multitude of interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than other factors in the overall outcome of the surgery. Future research into foot surgery should incorporate the complexity of how patients determine their outcome Disclosure statement: All authors have declared no conflicts of interes

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Regulation of Coronary Blood Flow

The heart is uniquely responsible for providing its own blood supply through the coronary circulation. Regulation of coronary blood flow is quite complex and, after over 100 years of dedicated research, is understood to be dictated through multiple mechanisms that include extravascular compressive forces (tissue pressure), coronary perfusion pressure, myogenic, local metabolic, endothelial as well as neural and hormonal influences. While each of these determinants can have profound influence over myocardial perfusion, largely through effects on end-effector ion channels, these mechanisms collectively modulate coronary vascular resistance and act to ensure that the myocardial requirements for oxygen and substrates are adequately provided by the coronary circulation. The purpose of this series of Comprehensive Physiology is to highlight current knowledge regarding the physiologic regulation of coronary blood flow, with emphasis on functional anatomy and the interplay between the physical and biological determinants of myocardial oxygen delivery. © 2017 American Physiological Society. Compr Physiol 7:321-382, 2017