The interaction of relativistically intense lasers with opaque targets represents a highly non-linear, multi-dimensional parameter space. This limits the utility of sequential 1D scanning of experimental parameters for the optimization of secondary radiation, although to-date this has been the accepted methodology due to low data acquisition rates. High repetition-rate (HRR) lasers augmented by machine learning present a valuable opportunity for efficient source optimization. Here, an automated, HRR-compatible system produced high-fidelity parameter scans, revealing the influence of laser intensity on target pre-heating and proton generation. A closed-loop Bayesian optimization of maximum proton energy, through control of the laser wavefront and target position, produced proton beams with equivalent maximum energy to manually optimized laser pulses but using only 60% of the laser energy. This demonstration of automated optimization of laser-driven proton beams is a crucial step towards deeper physical insight and the construction of future radiation sources.

We present the development and characterization of a high-stability, multi-material, multi-thickness tape-drive target for laser-driven acceleration at repetition rates of up to 100 Hz. The tape surface position was measured to be stable on the sub-micrometre scale, compatible with the high-numerical aperture focusing geometries required to achieve relativistic intensity interactions with the pulse energy available in current multi-Hz and near-future higher repetition-rate lasers ($>$kHz). Long-term drift was characterized at 100 Hz demonstrating suitability for operation over extended periods. The target was continuously operated at up to 5 Hz in a recent experiment for 70,000 shots without intervention by the experimental team, with the exception of tape replacement, producing the largest data-set of relativistically intense laser–solid foil measurements to date. This tape drive provides robust targetry for the generation and study of high-repetition-rate ion beams using next-generation high-power laser systems, also enabling wider applications of laser-driven proton sources.

A machine learning model was created to predict the electron spectrum generated by a GeV-class laser wakefield accelerator. The model was constructed from variational convolutional neural networks, which mapped the results of secondary laser and plasma diagnostics to the generated electron spectrum. An ensemble of trained networks was used to predict the electron spectrum and to provide an estimation of the uncertainty of that prediction. It is anticipated that this approach will be useful for inferring the electron spectrum prior to undergoing any process that can alter or destroy the beam. In addition, the model provides insight into the scaling of electron beam properties due to stochastic fluctuations in the laser energy and plasma electron density.

Humpback whales (Megaptera novaeangliae) exhibit maternally driven fidelity to feeding grounds, and yet occasionally occupy new areas. Humpback whale sightings and mortalities in the New York Bight apex (NYBA) have been increasing over the last decade, providing an opportunity to study this phenomenon in an urban habitat. Whales in this area overlap with human activities, including busy shipping traffic leading into the Port of New York and New Jersey. The site fidelity, population composition and demographics of individual whales were analysed to better inform management in this high-risk area. Whale watching and other opportunistic data collections were used to identify 101 individual humpback whales in the NYBA from spring through autumn, 2012–2018. Although mean occurrence was low (2.5 days), mean occupancy was 37.6 days, and 31.3% of whales returned from one year to the next. Individuals compared with other regional and ocean-basin-wide photo-identification catalogues (N = 52) were primarily resighted at other sites along the US East Coast, including the Gulf of Maine feeding ground. Sightings of mother-calf pairs were rare in the NYBA, suggesting that maternally directed fidelity may not be responsible for the presence of young whales in this area. Other factors including shifts in prey species distribution or changes in population structure more broadly should be investigated.

Typical enteropathogenic Escherichia coli (tEPEC) infection is a major cause of diarrhoea and contributor to mortality in children <5 years old in developing countries. Data were analysed from the Global Enteric Multicenter Study examining children <5 years old seeking care for moderate-to-severe diarrhoea (MSD) in Kenya. Stool specimens were tested for enteric pathogens, including by multiplex polymerase chain reaction for gene targets of tEPEC. Demographic, clinical and anthropometric data were collected at enrolment and ~60-days later; multivariable logistic regressions were constructed. Of 1778 MSD cases enrolled from 2008 to 2012, 135 (7.6%) children tested positive for tEPEC. In a case-to-case comparison among MSD cases, tEPEC was independently associated with presentation at enrolment with a loss of skin turgor (adjusted odds ratio (aOR) 2.08, 95% confidence interval (CI) 1.37–3.17), and convulsions (aOR 2.83, 95% CI 1.12–7.14). At follow-up, infants with tEPEC compared to those without were associated with being underweight (OR 2.2, 95% CI 1.3–3.6) and wasted (OR 2.5, 95% CI 1.3–4.6). Among MSD cases, tEPEC was associated with mortality (aOR 2.85, 95% CI 1.47–5.55). This study suggests that tEPEC contributes to morbidity and mortality in children. Interventions aimed at defining and reducing the burden of tEPEC and its sequelae should be urgently investigated, prioritised and implemented.

Background: Spinal muscular atrophy (SMA) is a children’s neuromuscular disorder. Although motor neuron loss is a major feature of the disease, we have identified fatty acid abnormalities in SMA patients and in preclinical animal models, suggesting metabolic perturbation is also an important component of SMA. Methods: Biochemical, histological, proteomic, and high resolution respirometry were used. Results: SMA patients are more susceptible to dyslipidemia than the average population as determined by a standard lipid profile in a cohort of 72 pediatric patients. As well, we observed a non-alcoholic liver disease phenotype in apreclinical mouse model. Denervation alone was not sufficient to induce liver steatosis, as a mouse model of ALS, did not develop fatty liver. Hyperglucagonemia in Smn2B/-mice could explain the hepatic steatosis by increasing plasma substrate availability via glycogen depletion and peripheral lipolysis. Proteomic analysis identified mitochondrion and lipid metabolism as major clusters. Alterations in mitochondrial function were revealed by high-resolution respirometry. Finally, low-fat diets led to increased survival in Smn2B/-mice. Conclusions: These results provide strong evidence for lipid metabolism defects in SMA. Further investigation will be required to establish the primary mechanism of these alterations and understand how they lead to additional co-morbidities in SMA patients.

This study analyzes the use and profitability of three distinct feeding systems; confinement feeding, traditional grazing, and management-intensive grazing from a randomly selected sample of northeastern dairy farms. The confinement feeding farms were significantly larger and produced more milk per cow, while the farms using management-intensive grazing incurred the lowest production costs. Both confinement feeding and management-intensive grazing generated significantly higher rates of return to farm assets relative to farms using a mixed system. Multiple regression analysis confirms the critical importance of herd size, milk production per cow, debt level and veterinary expenses to farm profitability in all production systems.

A financial training program designed by Cooperative Extension specialists was provided to over 2,000 USDA/FSA borrowers from the Northeast during the period 1994–1999. Key to the success of the workshops was an in-depth, user-friendly curriculum that evolved over time, eventually replacing satellite-feed instruction with pre-taped videos. Cluster analysis classified nearly 70% of workshop participants as “Low Finance Priority” or “Low Finance Knowledge.” Farmers in these clusters received a relatively greater educational benefit from the program than those not in these clusters. Impact analysis indicated that perceived annual gain in farm net worth from application of workshop tools ranged from approximately $5,000 to $10,000. The training addressed the needs of producers typically isolated from Cooperative Extension because the workshop was the only extension program attended that year by nearly two-thirds of them.

Introduction: In 2006, Alberta implemented an Electronic Health Record called the Alberta Netcare Portal (ANP). The ANP provides provincial read-only access to lab tests, diagnostic imaging, medication information and numerous text reports. There is no computerized order entry, and care is coordinated using a hybrid of paper charting and various electronic systems. Here, we quantify observed ANP use by physician participants providing care in four urban Emergency Departments (EDs) in Alberta. The results form part of a larger mixed methods research project aimed at detecting broader implications of ANP use for patient care. Methods: Between October 2014 and July 2015, ED physicians at four EDs (University of Alberta Hospital [UAH], Grey Nuns Community Hospital [GNCH], Foothills Medical Centre [FMC], Peter Lougheed Centre [PLC]) participated in structured clinical observations. Observations were purposively sampled during the first hours of shifts, when physicians orient themselves to the patients they will see during the rest of their shift, including reviewing available historic patient information. Observers used a tablet based tool to generate a time-stamped record of the information tools used alongside patient care. Information tools included permanent paper records, paper excluding permanent documentation, the ANP, clinical and other applications accessed via desktop computers, and mobile devices. Observers also recorded contextual data, including participant commentary, on paper field notes. Results: Across the 4 sites, 142 physicians participated in 376 sessions for a total of 566 observed physician-hours. Participants accessed information in different computerized applications and on paper (i.e., a ‘hybrid’ care environment). The highest proportion of observed physician time interacting with ANP was observed at the UAH (7.0%-8.1%, all values 95% Confidence Intervals). Physicians spent less time using ANP at GNCH (4.1%-4.8%), which was similar to the Calgary EDs (FMC: 4.4-5.3% and PLC: 5.2%-5.9%). Thematic analysis of field notes showed that ANP acceptance was very high. Patient safety concerns were recorded related to care provided alongside ‘hybrid’ patient records. Conclusion: We found high physician acceptance of ANP based on documented comments and observed usage. We posit a high potential for EHRs such as ANP to support improved care coordination which remains partly realized.

In the pediatric clinical setting, the parent/guardian will almost always be the authorized representative and designated recipient of clinical and research results, making the issue of to whom results should be returned in the pediatric setting less complex than in adult settings. It is also clear that, in genomic research related to pediatric diseases such as cancer, results may be of considerable clinical, ethical, and personal significance for parents in a number of ways, including a genomic explanation of the origin of their child’s cancer, implications for the genetic testing and medical care of other siblings and of the parents themselves, and reproductive planning with regard to the recurrence risk for future children to have an increased risk of cancer. However, what remains unclear is which results should be disclosed, and under what circumstances, to parents of deceased children.

The incidence of recreational water-associated outbreaks in the United States has significantly increased, driven, at least in part, by outbreaks both caused by Cryptosporidium and associated with treated recreational water venues. Because of the parasite's extreme chlorine tolerance, transmission can occur even in well-maintained treated recreational water venues (e.g. pools) and a focal cryptosporidiosis outbreak can evolve into a community-wide outbreak associated with multiple recreational water venues and settings (e.g. childcare facilities). In August 2004 in Auglaize County, Ohio, multiple cryptosporidiosis cases were identified and anecdotally linked to pool A. Within 5 days of the first case being reported, pool A was hyperchlorinated to achieve 99·9% Cryptosporidium inactivition. A case-control study was launched to epidemiologically ascertain the outbreak source 11 days later. A total of 150 confirmed and probable cases were identified; the temporal distribution of illness onset was peaked, indicating a point-source exposure. Cryptosporidiosis was significantly associated with swimming in pool A (matched odds ratio 121·7, 95% confidence interval 27·4–∞) but not with another venue or setting. The findings of this investigation suggest that proactive implementation of control measures, when increased Cryptosporidium transmission is detected but before an outbreak source is epidemiologically ascertained, might prevent a focal cryptosporidiosis outbreak from evolving into a community-wide outbreak.

Given the largely prefrontostriatal neuropathogenesis of HIV-associated neurobehavioral deficits, it is often presumed that HIV infection leads to greater impairment on letter versus category fluency. A meta-analysis of the HIV verbal fluency literature was conducted (k = 37, n = 7110) to assess this hypothesis and revealed generally small effect sizes for both letter and category fluency, which increased in magnitude with advancing HIV disease severity. Across all studies, the mean effect size of category fluency was slightly larger than that of letter fluency. However, the discrepancy between category and letter fluency dissipated in a more conservative analysis of only those studies that included both tests. Thus, HIV-associated impairments in letter and category fluency are of similar magnitude, suggesting that mild word generation deficits are evident in HIV, regardless of whether traditional letter or semantic cues are used to guide the word search and retrieval process (JINS, 2007, 13, 183–189.)

Cortical spreading depression (CSD) and peri-infarct depolarisation (PID) are related phenomena that have been associated with the human clinical syndromes of migraine (CSD), head injury and stroke (PID). Nevertheless the existence of CSD in man remains controversial, despite the detection of this phenomenon in the brains of most, if not all, other animal species investigated. This failure to unambiguously detect CSD clinically may be at least partly due to the anatomically complex, gyrencephalic structure of the human brain. This study was designed to establish conditions for the study of CSD in the brain of a gyrencephalic species using the noninvasive technique of magnetic resonance imaging (MRI). The 3-dimensional (3D) gyrencephalic anatomy of the cat brain was examined to determine the imaging conditions necessary to detect CSD events. Orthogonal transverse, sagittal and horizontal T1-weighted image slices showed that the marginal and suprasylvian gyri were the most appropriate cortical structures to study CSD. This was in view of (1) their simple geometry: (2) their lengthy extent of grey matter orientated rostrocaudally in the cortex: (3) their separation by a sulcus across which CSD spread could be studied and (4) the discontinuity in the grey matter in these regions between the right and left hemispheres dorsal to the corpus callosum. The structure suggested by the T1-weighted images was corroborated by systematic diffusion tensor imaging to map the fractional anisotropy and diffusion trace. Thus a single horizontal image plane could visualise the neighbouring suprasylvian and marginal gyri of both cerebral hemispheres, whereas its complex shape and position ruled out the ectosylvian gyrus for CSD studies. With the horizontal imaging plane, CSD events were reproducibly detected by animating successive diffusion-weighted MR images following local KCl stimulation of the cortical surface. In single image frames, CSD detection and characterisation required image subtraction or statistical mapping methods that, nevertheless, yielded concordant results. In repeat experiments, CSD events were qualitatively similar in appearance whether elicited by sustained or transient KCl applications. Our experimental approach thus successfully describes cat brain anatomy in vivo, and elucidates the necessary conditions for the application of MRI methods to detect CSD propagation.

The Burst and All Sky Imaging Survey (BASIS) is a proposed mission to provide ∼3 arc second locations of approximately 90 Gamma-Ray Bursts (GRBs) per year. The BASIS coded aperture imaging system requires a segmented detector plane able to detect the interaction position of (10 - 150 keV) photons to less than 100 μm. To develop prototype detector arrays with such fine position resolution we have fabricated many 15 mm × 15 mm × 2 mm 100 μm pitch CdZnTe strip detectors. We have assembled these fine pitch CdZnTe strip detectors into prototype 2 × 2 and 6 × 6 element arrays read out by ASIC electronics. The assembly and electronics readout of the 6 × 6 flight prototype array will be discussed, and preliminary data illustrating the uniformity and efficiency of the array will be presented.

A CdZnTe strip detector large area array (∼ 60 cm2 with 36 detectors) with capabilities for high resolution imaging and spectroscopy has been built as a prototype for a space flight gamma ray burst instrument. The detector array also has applications in nuclear medical imaging. Two dimensional orthogonal strip detectors with 100 μm pitch have been fabricated and tested. Details for the array design, fabrication and evaluation of the detectors will be presented.

A CdZnTe strip detector large area array (∼ 60 cm2 with 36 detectors) with capabilities for high resolution imaging and spectroscopy has been built as a prototype for a space flight gamma ray burst instrument. The detector array also has applications in nuclear medical imaging. Two dimensional orthogonal strip detectors with 100 gm pitch have been fabricated and tested. Details for the array design, fabrication and evaluation of the detectors will be presented.

The binding of propranolol by a perfluorochemical emulsion (PFCE), cXiacid glycoprotein (AGP), and their mixtures was examined by a dialysis exchange method at 37°C. A sedimentation method was used to verify propranolol binding by the PFCE. Binding of 100 and 500 ng/ml drug by 100, 75, 50 and 25% v/v concentrations of the PFCE or of 0.067% AGP was determined. Propranolol was highly bound by the PFCE with a percent free propranolol in undiluted PFCE of 13.1% at both 100 and 500 ng/ml propranolol. Propranolol was moderately bound by AGP. The percent free propranolol in 0.067% AGP was 31.4% and 32.4% for 100 and 500 ng/ml propranolol, respectively. The percent bound propranolol was not significantly different when the emulsion was diluted to 75 and 50% v/v with 0.067% AGP solution rather than buffer. When the PFCE was further diluted to 25% v/v with the 0.067% AGP solution the percent free propranolol was significantly lower than in the 25% v/v PFCE alone or 75% v/v protein solution alone. Thus, the PFCE has a relatively large affinity and capacity for propranolol. Propranolol did not partition from buffer to the PFC liquid. This indicates that propranolol bound by the PFCE is associated only with the emulsifiers.