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The Medicare Hospice Benefit increasingly serves people dying with dementia. We sought to understand characteristics, hospice use patterns, and last-month-of-life care quality ratings among hospice enrollees with dementia coexisting with another terminal illness as compared to enrollees with a principal hospice diagnosis of dementia, and enrollees with no dementia.We conducted a pooled cross-sectional study among decedent Medicare beneficiaries age 70+ using longitudinal data from the National Health and Aging Trends Study (NHATS) (last interview before death; after-death proxy interview) linked to Medicare hospice claims (2011-2017). We used unadjusted and adjusted regression analyses to compare characteristics of hospice enrollees with coexisting dementia to two groups: (1) enrollees with a principal dementia diagnosis, and (2) enrollees with no dementia.Among 1105 decedent hospice enrollees age 70+, 40% had coexisting dementia, 16% had a principal diagnosis of dementia, and 44% had no dementia. In adjusted analyses, enrollees with coexisting dementia had high rates of needing help with 3-6 activities of daily living, similar to enrollees with principal dementia (62% vs. 67%). Enrollees with coexisting dementia had high clinical needs, similar to those with no dementia, for example, 63% versus 61% had bothersome pain. Care quality was worse for enrollees with coexisting dementia versus principal dementia (e.g., 61% vs. 79% had anxiety/sadness managed) and similar to those with no dementia. Enrollees with coexisting dementia had similar hospice use patterns as those with principal diagnoses and higher rates of problematic use patterns compared to those with no dementia (e.g., 16% vs. 10% live disenrollment, p = 0.004).People with coexisting dementia have functional needs comparable to enrollees with principal diagnoses of dementia, and clinical needs comparable to enrollees with no dementia. Changes to hospice care models and policy may be needed to ensure appropriate dementia care.

The rate response of PET-hydrolases to increased substrate crystallinity (XC) of poly(ethylene terephthalate) (PET) manifests as a rate-lowering effect that varies significantly for different enzymes. Herein, we report the influence of XC on the product release rate of six thermostable PET-hydrolases. All enzyme reactions displayed a distinctive lag phase until measurable product formation occurred. The duration of the lag phase increased with XC. The recently discovered PET-hydrolase PHL7 worked efficiently on “amorphous” PET disks (XC ∼10, but this enzyme was extremely sensitive to increased XC, whereas the enzymes LCCICCG, LCC, and DuraPETase had higher tolerance to increases in XC and had activity on PET disks having XC of 24.4 during reaction. Structural and molecular dynamics analysis of the PET-hydrolyzing enzymes disclosed that surface electrostatics and enzyme flexibility may account for the observed differences.

Environmental water management often benefits from a risk-based approach where information on the area of interest is characterized, assembled, and incorporated into a decision model considering uncertainty. This includes prior information from literature, field measurements, professional interpretation, and data assimilation resulting in a decision tool with a posterior uncertainty assessment accounting for prior understanding and what is learned through model development and data assimilation. Model construction and data assimilation are time consuming and prone to errors, which motivates a repeatable workflow where revisions resulting from new interpretations or discovery of errors can be addressed and the analyses repeated efficiently and rigorously. In this work, motivated by the real world application of delineating risk-based (probabilistic) sources of water to supply wells in a humid temperate climate, a scripted workflow was generated for groundwater model construction, data assimilation, particle-tracking and post-processing. The workflow leverages existing datasets describing hydrogeology, hydrography, water use, recharge, and lateral boundaries. These specific data are available in the United States but the tools can be applied to similar datasets worldwide. The workflow builds the model, performs ensemble-based history matching, and uses a posterior Monte Carlo approach to provide probabilistic capture zones describing source water to wells in a risk-based framework. The water managers can then select areas of varying levels of protection based on their tolerance for risk of potential wrongness of the underlying models. All the tools in this workflow are open-source and free, which facilitates testing of this repeatable and transparent approach to other environmental problems.

Realistic environmental models used for decision making typically require a highly parameterized approach. Calibration of such models is computationally intensive because widely used parameter estimation approaches require individual forward runs for each parameter adjusted. These runs construct a parameter-to-observation sensitivity, or Jacobian, matrix used to develop candidate parameter upgrades. Parameter estimation algorithms are also commonly adversely affected by numerical noise in the calculated sensitivities within the Jacobian matrix, which can result in unnecessary parameter estimation iterations and less model-to-measurement fit. Ideally, approaches to reduce the computational burden of parameter estimation will also increase the signal-to-noise ratio related to observations influential to the parameter estimation even as the number of forward runs decrease. In this work a simultaneous increments, an iterative ensemble smoother (IES), and a randomized Jacobian approach were compared to a traditional approach that uses a full Jacobian matrix. All approaches were applied to the same model developed for decision making in the Mississippi Alluvial Plain, USA. Both the IES and randomized Jacobian approach achieved a desirable fit and similar parameter fields in many fewer forward runs than the traditional approach; in both cases the fit was obtained in fewer runs than the number of adjustable parameters. The simultaneous increments approach did not perform as well as the other methods due to inability to overcome suboptimal dropping of parameter sensitivities. This work indicates that use of highly efficient algorithms can greatly speed parameter estimation, which in turn increases calibration vetting and utility of realistic models used for decision making.

BACKGROUND: Hospice patients with dementia are at increased risk for live discharge and long lengths of stay (>180 days), causing patient and family caregiver stress and burden. The location and timing of clinician visits are important factors influencing whether someone dies as expected, in hospice, or experiences a live discharge or long length of stay. OBJECTIVE: Examine how home hospice and nurse visit frequency relate to dying in hospice within the Medicare-intended 6-month period. DESIGN: Retrospective cohort study. SETTING: Non-profit hospice agency. PARTICIPANTS: Three thousand eight hundred and thirty seven patients with dementia who received hospice services from 2013 to 2017. METHODS: Multivariable survival analyses examined the effects of receiving home hospice (vs. nursing home) and timing of nurse visits on death within 6 months of hospice enrollment, compared to live discharge or long length of stay. Models adjust for relevant demographic and clinical factors. RESULTS: Thirty-nine percent (39%) of patients experienced live discharge or long length of stay. Home hospice patients were more likely to experience live discharge or long length of stays (HR for death: 0.77, 95%CI: 0.69–0.86, p < 0.001). Frequency of nurse visits was inversely associated with live discharge and long lengths of stay (HR for death: 2.87, 95%CI: 2.47–3.33, p < 0.001). CONCLUSION: Nearly 40% of patients with dementia in our study experienced live discharge or a long length of stay. Additional research is needed to understand why home hospice may result in live discharge or a long length of stay for patients with dementia. Nurse visits were associated with death, suggesting their responsiveness to deteriorating patient health. Hospice guidelines may need to permit longer stays so community-dwelling patients with dementia, a growing segment of hospice patients, can remain continuously enrolled in hospice and avoid burden and costs associated with live discharge.

Background The homeless patient population is known to have a high occurrence of inappropriate emergency department (ED) utilization. The study hospital initiated a dedicated homeless clinic targeting patients experiencing homelessness with a combination of special features. We aim to determine whether this mode of care can reduce inappropriate ED utilization among homeless patients. Methods We conducted a retrospective observational study from July 1, 2017 to Dec 31, 2017. The study enrolled all homeless patients who visited any hospital regular clinic, dedicated homeless clinic, and ED at least once during the study period. ED homeless patients were divided into four groups (A: no clinic visits; B: those who only visited hospital regular clinic; C: those who only visited dedicated homeless clinic; and D: those who visited both hospital regular clinic and dedicated homeless clinic). The New York University algorithm was used to determine appropriate ED utilization. We compared inappropriate ED utilization among patients from these groups. Multivariate logistic regression was used to determine the risks of different clinical visits in association with inappropriate ED utilization. Results A total of 16,323 clinic and 8511 ED visits occurred among 5022 unique homeless patients, in which 2450 unique patients were seen in hospital regular clinic, 784 patients in dedicated homeless clinic, 688 patients in both hospital regular clinic and dedicated homeless clinic, and 1110 patients with no clinic visits. Twenty‐nine percent (230/784) of patients from dedicated homeless clinic utilized the ED, among which 21% (175/844) of their ED visits were considered inappropriate. In contrast, 40% of patients from hospital regular clinic utilized the ED, among which 29% were inappropriate (P < 0.001). The adjusted odds ratio (OR) was 0.61 (95% confidence interval [CI] = 0.50–0.74, P < 0.001) on dedicated homeless clinic predicting inappropriate ED visits in multivariate logistic regression. Conclusion Implementing a dedicated homeless clinic with these features can reduce ED inappropriate utilization among patients experiencing homelessness.

Those who are infected with Severe Acute Respiratory Syndrome‐related CoronaVirus‐2 are theoretically at increased risk of venous thromboembolism during self‐isolation if they have reduced mobility or are dehydrated. Should patients develop coronavirus disease (COVID‐19) pneumonia requiring hospital admission for treatment of hypoxia, the risk for thromboembolic complications increases greatly. These thromboembolic events are the result of at least two distinct mechanisms – microvascular thrombosis in the pulmonary system (immunothrombosis) and hospital‐associated venous thromboembolism. Since pregnancy is a prothrombotic state, there is concern regarding the potentially increased risk of thrombotic complications among pregnant women with COVID‐19. To date, however, pregnant women do not appear to have a substantially increased risk of thrombotic complications related to COVID‐19. Nevertheless, several organizations have vigilantly issued pregnancy‐specific guidelines for thromboprophylaxis in COVID‐19. Discrepancies between these guidelines reflect the altruistic wish to protect patients and lack of high‐quality evidence available to inform clinical practice. Low molecular weight heparin (LMWH) is the drug of choice for thromboprophylaxis in pregnant women with COVID‐19. However, its utility in non‐pregnant patients is only established against venous thromboembolism, as LMWH may have little or no effect on immunothrombosis. Decisions about initiation and duration of prophylactic anticoagulation in the context of pregnancy and COVID‐19 must take into consideration disease severity, outpatient vs inpatient status, temporal relation between disease occurrence and timing of childbirth, and the underlying prothrombotic risk conferred by additional comorbidities. There is currently no evidence to recommend the use of intermediate or therapeutic doses of LMWH in thromboprophylaxis, which may increase bleeding risk without reducing thrombotic risk in pregnant patients with COVID‐19. Likewise, there is no evidence to comment on the role of low‐dose aspirin in thromboprophylaxis or of anti‐cytokine and antiviral agents in preventing immunothrombosis. These unanswered questions are being studied within the context of clinical trials.

Accurately accounting for flows of energy through food webs is challenging because of the spatial and temporal variability associated with energy production and consumption. Wet–dry tropical rivers have a highly seasonal discharge regime where wet season flows allow access to energy sources (inundated wetlands) that are not available during the dry season when aquatic consumers are confined to disconnected waterholes. We combined measures of fish community biomass with previously published feeding guild specific stable isotope analyses to explore how opposing wet- and dry-season habitat templates influence spatial and temporal trends in the sources of energy supporting fish biomass throughout a river network in the wet–dry tropics of northern Australia. Accounting for the relative contribution of each feeding guild to fish community biomass was a critical component of our analyses, as a single feeding guild (invertivore/piscivore) influenced spatial and temporal patterns in the sources of energy supporting overall fish biomass. During the early dry season, the reliance of fish communities on autochthonous sources of energy (periphyton) decreased from the upper to lower reaches of the river network, which correlates with increasing floodplain area and wet season inundation times. These patterns disappeared by the late dry season as fish in both upper and lower reaches became increasingly reliant on autochthonous sources produced within waterholes over the course of the dry season, indicating that the large wet-season gains in fish biomass are maintained through the dry season by energy produced within waterhole refuges. Collectively these results indicate that a combination of autochthonous and allochthonous sources of energy work in unison to support fish community biomass throughout the Mitchell River catchment and that access to these sources of energy is dictated by seasonal patterns in discharge interacting with spatial variability in river geomorphology (channel geometry and floodplain area). Many rivers are experiencing decreased flows due to water resource development and more frequent and severe droughts. Thus, we suggest our study provides insight into how changes in discharge regime could influence food web energetics throughout river networks.

Summary This document aims to provide practical guidance for the assessment and management of patients with thrombocytopenia, with a particular focus on immune thrombocytopenia (ITP), during the COVID‐19 pandemic. The intention is to support clinicians and, although recommendations have been provided, it is not a formal guideline. Nor is there sufficient evidence base to conclude that alternative approaches to treatment are incorrect. Instead, it is a consensus written by clinicians with an interest in ITP or coagulation disorders and reviewed by members of the UK ITP forum.

The level of venous thrombosis risk in women who experience spontaneous or induced pregnancy loss has previously been uncertain. However, recent data indicate that the risk of venous thrombosis in women undergoing pregnancy termination in the first trimester is increased two-fold compared to non-pregnant women but reduced five-fold compared to women in the 6 weeks following a term birth. The termination procedure itself appears not to influence thrombosis risk. In light of this data, this consensus statement provides recommendations for reducing the risk of venous thrombosis in women undergoing spontaneous or induced pregnancy loss based on Royal College of Obstetricians and Gynaecologists risk stratification guidelines.

Wound healing is a complex process involving multiple independent and overlapping sequential physiological mechanisms. In addition to cutaneous injury, a severe burn stimulates physiological derangements that induce a systemic hypermetabolic response resulting in impaired wound healing. Topical application of the anti-androgen drug, flutamide accelerates cutaneous wound healing, whereas paradoxically systemic dihydrotestosterone (DHT) improves burn wound healing. We developed and characterized a PCL scaffold that is capable of controlled release of androgen (DHT) and anti-androgen (F) individually or together. This study aims to investigate whether local modification of androgen actions has an impact on burn injury wound healing. In a full-thickness burn wound healing, mouse model, DHT/F-scaffold showed a significantly faster wound healing compared with F-scaffold or DHT-scaffold. Histology analysis confirmed that DHT/F-scaffold exhibited higher re-epithelization, cell proliferation, angiogenesis, and collagen deposition. Dual release of DHT and F from PCL scaffolds promoted cell proliferation of human keratinocytes and alters the keratinocyte cell cycle. Lastly, no adverse effects on androgen-dependent organs, spleen and liver were observed. In conclusion, we demonstrated DHT plus F load PCL scaffolds accelerated burn wound healing when loading alone did not. These findings point to a complex role of androgens in burn wound healing and open novel therapeutic avenues for treating severe burn patients.

Background Hypertensive disorders of pregnancy (HDP) and pre‐pregnancy hypertension are associated with increased morbidity and mortality for the mother. Our aim was to investigate the relationships between HDP and pre‐pregnancy hypertension with maternal heart failure (HF) within 1 and 5 years of delivery and to examine racial/ethnic differences. Methods and Results We conducted a retrospective cohort study in South Carolina (2004–2016) involving 425 649 women aged 12 to 49 years (58.9% non‐Hispanic White [NHW], 31.5% non‐Hispanic Black [NHB], 9.6% Hispanic) with a live, singleton birth. Incident HF was defined by hospital/emergency department visit and death certificate data. Pre‐pregnancy hypertension and HDP (preeclampsia, eclampsia, or gestational hypertension) were based on hospitalization/emergency department visit and birth certificate data (i.e., gestational hypertension for HDP). The 425 649 women had pre‐pregnancy hypertension without superimposed HDP (pre‐pregnancy hypertension alone; 0.4%), HDP alone (15.7%), pre‐pregnancy hypertension with superimposed HDP (both conditions; 2.2%), or neither condition in any pregnancy (81.7%). Incident HF event rates per 1000 person‐years were higher in NHB than NHW women with HDP (HDP: 2.28 versus 0.96; both conditions: 4.30 versus 1.22, respectively). After adjustment, compared with women with neither condition, incident HF risk within 5 years of delivery was increased for women with pre‐pregnancy hypertension (HR,2.55, 95% CI: 1.31–4.95), HDP (HR,4.20, 95% CI: 3.66–4.81), and both conditions (HR,5.25, 95% CI: 4.24–6.50). Conclusions Women with HDP and pre‐pregnancy hypertension were at higher HF risk (highest for superimposed preeclampsia) within 5 years of delivery. NHB women with HDP had higher HF risk than NHW women, regardless of pre‐pregnancy hypertension.

Protection of fens–wetlands dependent on groundwater discharge–requires characterization of groundwater sources and stresses. Because instrumentation and numerical modeling of fens is labor intensive, easy‐to‐apply methods that model fen distribution and their vulnerability to development are desirable. Here we demonstrate that fen areas can be simulated using existing steady‐state MODFLOW models when the unsaturated zone flow (UZF) package is included. In cells where the water table is near land surface, the UZF package calculates a head difference and scaled conductance at these “seepage drain” cells to generate average rates of vertical seepage to the land. This formulation, which represents an alternative to blanketing the MODFLOW domain with drains, requires very little input from the user because unsaturated flow‐routing is inactive and results are primarily driven by easily obtained topographic information. Like the drain approach, it has the advantage that the distribution of seepage areas is not predetermined by the modeler, but rather emerges from simulated heads. Beyond the drain approach, it takes account of intracell land surface variation to explicitly quantify multiple surficial flows corresponding to infiltration, rejected recharge, recharge and land‐surface seepage. Application of the method to a basin in southeastern Wisconsin demonstrates how it can be used as a decision‐support tool to first, reproduce fen distribution and, second, forecast drawdown and reduced seepage at fens in response to shallow pumping., Article impact statement: Protection of fens is improved by enhanced fen‐groundwater exchange simulation provided by this easy‐to‐apply approach.

This illustrated review discusses the haemostatic changes seen in patients with severe coronavirus disease 2019 (COVID‐19) infection and their possible causes. We discuss the crosstalk between inflammation and coagulation resulting in high levels of acute‐phase proteins, very high levels of D‐dimers, and absence of disseminated intravascular coagulation seen in patients with severe COVID‐19. There appear to be high rates of venous thromboembolism and also, what has been poorly described before in acute lung injury, a high rate of pulmonary immunothrombosis (thrombosis secondary to inflammation).

Since its conception, the periodic table and the elements contained within it have shaped our modern lives. The use of many elements is now ubiquitous and essential for the modern technologies we have now become accustomed to. However, our use of some elements may be considered as unsustainable and their current use may create both economic and environmental pressures. The United Nations have designated 2019 the "International Year of the Periodic Table". As such this Essay presents some important points on "critical elements" and the importance of adopting sustainable practices in the use of all elements of the periodic table. This article also highlights a number of examples of green technologies for elemental recovery and some of the challenges we must overcome to become truly sustainable across the whole periodic table.

Introduction The purpose of this study was to identify existing US midwifery fellowships and their key attributes. Methods The study team adapted an internet-search methodology that was recently used to identify nurse practitioner fellowships and residencies and identified 1) search terms likely to locate websites describing or promoting midwifery fellowship or residency programs and 2) program attributes likely to be outlined in the websites. Two investigators conducted full, independent Google searches and then reconciled minor differences in terminology and findings via teleconference and simultaneous reviews of websites. Results Eight programs were identified that had sufficient information on a website to clearly establish them as midwifery fellowship programs. No programs used the term residency. The fellowship programs tended to be located in the western United States and predominantly focused on newly graduated certified nurse-midwives. Four programs were operated by university units, with the clinical experience located in the hospital. Four programs were operated by birth centers, with the clinical experience obtained in a combination of birth center, home, and/or hospital setting. Typical program lengths varied but were reported to be about 12 months. Discussion This study offers baseline information on the current midwifery fellowship offerings available via public internet search. This study also identifies key attributes of fellowships that may be helpful to stakeholders as they consider the role of fellowships for midwifery graduates and any need for accountability, such as accreditation review, among the programs.

Fecal contamination by human and animal pathogens, including viruses, bacteria, and protozoa, is a potential human health hazard, especially with regards to drinking water. Pathogen occurrence in groundwater varies considerably in space and time, which can be difficult to characterize as sampling typically requires hundreds of liters of water to be passed through a filter. Here we describe the design and deployment of an automated sampler suited for hydrogeologically and chemically dynamic groundwater systems. Our design focused on a compact form to facilitate transport and quick deployment to municipal and domestic water supplies. We deployed a sampler to characterize water quality from a household well tapping a shallow fractured dolomite aquifer in northeast Wisconsin. The sampler was deployed from January to April 2017, and monitored temperature, nitrate, chloride, specific conductance, and fluorescent dissolved organic matter on a minute time step; water was directed to sequential microbial filters during three recharge periods that ranged from 5 to 20 days. Results from the automated sampler demonstrate the dynamic nature of the household water quality, especially with regard to microbial targets, which were shown to vary 1 to 2 orders of magnitude during a single sampling event. We believe assessments of pathogen occurrence and concentration, and related assessments of drinking well vulnerability, would be improved by the time-integrated characterization provided by this sampler.

The United States Navy uses a visual feedback system for pilots, named 'the Greenie Board', to improve flight manoeuvres on aircraft carriers. Given that increased compliance with enhanced recovery after surgery protocols reduces postoperative complications, we decided to apply a similar feedback system to our institutional enhanced recovery programme. We undertook a prospective 12-month audit of 194 patients assigned to our enhanced recovery programme and evaluated adherence to the anaesthesia-related components of our protocol, before and after implementing a Greenie Board. A compliance score was calculated by summing points for adherence to: intra-operative antibiotic prophylaxis; temperature management; goal-directed intravenous fluid therapy; postoperative nausea and vomiting prophylaxis; and postoperative fluid restriction. The score for each patient was then colour-coded and anonymously displayed for each anaesthetist on a Greenie Board within the operating theatre suite. Protocol adherence improved significantly following introduction, with 'Green' scores (acceptable compliance) increasing from 33% to 72% of patients (p < 0.0001). The greatest improvement was seen with anti-emetic prophylaxis (49% to 70%, p = 0.004) with a consequent reduction in postoperative nausea and vomiting (OR 0.42, 95% CI 0.19-0.88, p = 0.021). We did not observe a decrease in other postoperative complications nor hospital length of stay. We conclude that this US Navy-inspired feedback system is an easily implemented, low-cost quality improvement tool that significantly improved adherence to intra-operative components of our enhanced recovery protocol. The system lends itself to global scaling to drive quality improvement in healthcare delivery and would be suited to institutions without electronic medical records, including low-resource countries.

Background Management of adrenal incidentalomas (AI) is becoming more conservative, based on international data showing a low incidence of functional or malignant lesions. The clinical characteristics of AI in New Zealand are unknown. Therefore, whether the AI guidelines apply to the New Zealand population is also unknown. Aims To investigate the clinical characteristics of patients with AI presenting to a tertiary-care centre in New Zealand. Method This study prospectively evaluated consecutive patients aged 18 or older with AI, 1 cm or larger, diagnosed in Canterbury, New Zealand. A standardised nurse-led dedicated AI clinic was used, including clinical assessment, hormonal evaluation and imaging. Results From January 2010 to April 2016, 306 patients were referred to the AI clinic, 228 met the inclusion criteria. Most of those excluded were not true AI, due to imaging performed for known or suspected non-adrenal malignancy. The most common reason for imaging was abdominal pain (46%). Most cases were benign (96.5%) and 88.6% of all cases were non-functional. Of the functioning tumours (26 patients), 18 had subclinical Cushing syndrome, four had late-onset congenital adrenal hyperplasia, two had phaeochromocytoma and one had primary hyperaldosteronism. Three patients had primary adrenal cancer, one of whom was secreting excess cortisol. One adrenal metastasis was diagnosed. Conclusion This study found a similar prevalence of functional and malignant AI as international centres, although mild cortisol excess and primary aldosteronism may be under-represented. Therefore, the conservative approach to management of AI recommended in current guidelines is likely to be applicable to New Zealand population.

The duration of winter ice cover on lakes varies substantially with climate variability, and has decreased over the last several decades in many temperate lakes. However, little is known of how changes in seasonal ice cover may affect biogeochemical processes under ice. We examined winter nitrogen (N) dynamics under ice using a 30+ yr dataset from five oligotrophic/mesotrophic north temperate lakes to determine how changes in inorganic N species varied with ice duration. Nitrate accumulated during winter and was strongly related to the number of days since ice‐on. Exogenous inputs accounted for less than 3% of nitrate accumulation in four of the five lakes, suggesting a paramount role of nitrification in regulating N transformation and the timing of chemical conditions under ice. Winter nitrate accumulation rates ranged from 0.15 μg N L−1 d−1 to 2.7 μg N L−1 d−1 (0.011–0.19 μM d−1), and the mean for intermediate depths was 0.94 μg N L−1 d−1 (0.067 μM d−1). Given that winters with shorter ice duration (< 120 d) have become more frequent in these lakes since the late 1990s, peak winter nitrate concentrations and cumulative nitrate production under ice may be declining. As ice extent and duration change, the physical and chemical conditions supporting life will shift. This research suggests we may expect changes in the form and amount of inorganic N, and altered dissolved nitrogen : phosphorus ratios, in lakes during winters with shorter ice duration.

Summary Feedback control of heart rate (HR) for treadmills is important for exercise intensity specification and prescription. This work aimed to formulate HR control within a stochastic optimal control framework and to experimentally evaluate controller performance. A quadratic cost function is developed and linked to quantitative performance outcome measures, namely, root-mean-square tracking error and average control signal power. An optimal polynomial systems design is combined with frequency-domain analysis of feedback loop properties, with focus on the input sensitivity function, which governs the response to broad-spectrum HR variability disturbances. These, in turn, are modelled using stochastic process theory. A simple and approximate model of HR dynamics was used for the linear time-invariant controller design. Twelve healthy male subjects were recruited for comparative experimental evaluation of 3 controllers, giving 36 tests in total. The mean root-mean-square tracking error for the optimal controllers was around 2.2 beats per minute. Significant differences were observed in average control signal power for 2 different settings of the control weighting (mean power 22.6 vs 62.5×10−4 m2/s2, high vs low setting, p=2.3×10−5). The stochastic optimal control framework provides a suitable method for attainment of high-precision, stable, and robust control of HR during treadmill exercise. The control weighting can be used to set the balance between regulation accuracy and control signal intensity, and it has a clear and systematic influence on the shape of the input sensitivity function. Future work should extend the problem formulation to encompass low-pass compensator and input sensitivity characteristics.

Objectives To describe short-term and long-term survival of horses with duodenojejunal mesenteric rents, and to examine the association of selected preoperative, intraoperative, and postoperative factors with survival or colic after discharge, in horses with duodenojejunal mesenteric rents. Study Design Retrospective case series. Animals Horses undergoing surgery for correction of small intestinal lesions secondary to duodenojejunal mesenteric rents (n = 38). Methods Medical records (2006-2014) of horses admitted to a referral hospital in Kentucky were reviewed. Data for preoperative and intraoperative findings, postoperative complications, and short-term survival to discharge were recorded Long-term (>12 months) survival was determined by follow-up telephone query. Association of factors with survival and colic after discharge was determined using logistic regression. Results All 38 horses were Thoroughbred broodmares. Short-term survival was 76% overall and 88% among horses that recovered from general anesthesia. Long-term survival was 74% overall and 97% for mares that survived to discharge. All long-term survivors and 85% of mares that recovered from general anesthesia returned to use for breeding. The odds of survival were significantly higher for horses ≤10 years of age (OR = 6.2; 95% CI, 1.1-34.4). Failure to close the rent was associated with increased odds of colic after discharge, but had no effect on survival. Conclusion Short-term and long-term survival was high relative to prior reports and mares surviving to discharge following mesenteric rent surgery had an excellent prognosis for long-term survival. Based on our data, closure of rents is recommended to prevent recurrence of colic, but may be unnecessary for survival.

This is a meeting report of the 2019 Liver Sinusoid Meeting, 20th International Symposium on Cells of the Hepatic Sinusoid, held in Sydney, Australia, in September 2019. The meeting, which was organized by the International Society for Hepatic Sinusoidal Research, provided an update on the recent advances in the field of hepatic sinusoid cells in relation to cell biology, aging, and liver disease, with particular focus on the molecular and cellular targets involved in hepatic fibrosis, nonalcoholic hepatic steatohepatitis, alcoholic liver disease, hepatocellular carcinoma, and cirrhosis. In addition, the meeting highlighted the recent advances in regenerative medicine, targeted nanotechnologies, therapeutics, and novel methodologies., This is a meeting report of the presentations given at the 2019 Liver Sinusoid Meeting, 20th International Symposium on Cells of the Hepatic Sinusoid, organized by the International Society for Hepatic Sinusoidal Research (ISHSR), held in Sydney in September 2019.

The aim of this study was to investigate the effect of a pilot preclinical incentive program on dental students' performance on a clinical competency (mock board) exam at Midwestern University College of Dental Medicine-Arizona. To assess the effect of preclinical grade incentives in a program called SUCCEED, scores from a clinical competency exam administered during the fall quarter of the fourth year were compared between the graduating classes of 2014 and 2015 (pre-SUCCEED curriculum) and the graduating class of 2016 (post-SUCCEED curriculum). The study hypothesized that the class participating in the SUCCEED program, with its incentives for greater preclinical preparation and practice, would score higher than the other classes on the exams. The results showed that the endodontics and periodontics pass rates and test scores from the Class of 2016 were higher than those from the Classes of 2014 and 2015; the prosthodontics pass rates were similar; and the operative dentistry pass rates and test scores were lower than the Classes of 2014 and 2015. While the results of two of the four subsections of the competency exam showed an improvement in clinical performance for the Class of 2016, the operative dentistry test scores for that class were less than expected. Based on the increased number of operative dentistry procedures performed in preclinical simulation and the clinic, the authors conclude that the competency exam should not be the only measure to evaluate success of the SUCCEED program.

Open-source technology not only has facilitated the expansion of the greater research community, but by lowering costs it has encouraged innovation and customizable design. The field of automated microscopy has continued to be a challenge in accessibility due the expense and inflexible, noninterchangeable stages. This paper presents a low-cost, open-source microscope 3-D stage. A RepRap 3-D printer was converted to an optical microscope equipped with a customized, 3-D printed holder for a USB microscope. Precision measurements were determined to have an average error of 10 μm at the maximum speed and 27 μm at the minimum recorded speed. Accuracy tests yielded an error of 0.15%. The machine is a true 3-D stage and thus able to operate with USB microscopes or conventional desktop microscopes. It is larger than all commercial alternatives, and is thus capable of high-depth images over unprecedented areas and complex geometries. The repeatability is below 2-D microscope stages, but testing shows that it is adequate for the majority of scientific applications. The open-source microscope stage costs less than 3-9% of the closest proprietary commercial stages. This extreme affordability vastly improves accessibility for 3-D microscopy throughout the world.

One common factor across many economies around the world is their high dependency on petroleum. The chemical sector is no exception and considering the paramount role that solvents play within this industry they make an ideal focus for investigating green transition potential. This work attempts to shed some light on the scarce literature regarding the quantitative assessment of substitution capacity in target markets, by examining a case study of toluene use as an industrial cleaning agent and its replacement by limonene, a widely established citrus-peel-derived alternative in a number of applications. The systematic approach presented here compares market demand against potential supply by evaluating current and projected scenarios based on citrus fruit and juice production both at global and regional level. The results clearly show that the potential for complete substitution of toluene by limonene at global level is certainly out of reach, but encouraging results were obtained in specific regional substitution case studies, considering both citrus-producing and citrus-importing countries. In these cases, there is a clear potential for limonene to substitute toluene as a solvent within and beyond the cleaning sector, leaving space for future work in this area to investigate the transition potential for other important bio-based chemicals. © 2016 Society of Chemical Industry and John Wiley & Sons, Ltd

Anti-neutrophil cytoplasmic antibody vasculitis is a systemic autoimmune disease with glomerulonephritis and pulmonary haemorrhage as major clinical manifestations. The name reflects the presence of autoantibodies to myeloperoxidase and proteinase-3, which bind to both neutrophils and monocytes. Evidence of the pathogenicity of these autoantibodies is provided by the observation that injection of anti-myeloperoxidase antibodies into mice causes a pauci-immune focal segmental necrotizing glomerulonephritis which is histologically similar to the changes seen on renal biopsy in patients. Previous studies in this model have implicated the alternative pathway of complement activation and the anaphylatoxin C5a. Despite this progress, the factors that initiate complement activation have not been defined. In addition, the relative importance of bone marrow-derived and circulating C5 is not known. This is of interest given the recently identified roles for complement within leukocytes. We induced anti-myeloperoxidase vasculitis in mice and confirmed a role for complement activation by demonstrating protection in C3-deficient mice. We showed that neither MASP-2- nor properdin-deficient mice were protected, suggesting that alternative pathway activation does not require properdin or the lectin pathway. We induced disease in bone marrow chimaeric mice and found that circulating and not bone marrow-derived C5 was required for disease. We have therefore excluded properdin and the lectin pathway as initiators of complement activation and this means that future work should be directed at other potential factors within diseased tissue. In addition, in view of our finding that circulating and not bone marrow-derived C5 mediates disease, therapies that decrease hepatic C5 secretion may be considered as an alternative to those that target C5 and C5a. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

We recently showed that orexin expression in sudden infant death syndrome (SIDS) infants was reduced by 21% in the hypothalamus and by 40-50% in the pons as compared with controls. Orexin maintains wakefulness/sleeping states, arousal, and rapid eye movement sleep, abnormalities of which have been reported in SIDS. This study examined the effects of two prominent risk factors for SIDS, intermittent hypercapnic hypoxia (IHH) (prone-sleeping) and chronic nicotine exposure (cigarette-smoking), on orexin A (OxA) and orexin B (OxB) expression in piglets. Piglets were randomly assigned to five groups: saline control (n = 7), air control (n = 7), nicotine [2 mg/kg per day (14 days)] (n = 7), IHH (6 min of 7% O2 /8% CO2 alternating with 6-min periods of breathing air, for four cycles) (n = 7), and the combination of nicotine and IHH (N + IHH) (n = 7). OxA/OxB expression was quantified in the central tuberal hypothalamus [dorsal medial hypothalamus (DMH), perifornical area (PeF), and lateral hypothalamus], and the dorsal raphe, locus coeruleus of the pons. Nicotine and N + IHH exposures significantly increased: (i) orexin expression in the hypothalamus and pons; and (ii) the total number of neurons in the DMH and PeF. IHH decreased orexin expression in the hypothalamus and pons without changing neuronal numbers. Linear relationships existed between the percentage of orexin-positive neurons and the area of pontine orexin immunoreactivity of control and exposure piglets. These results demonstrate that postnatal nicotine exposure increases the proportion of orexin-positive neurons in the hypothalamus and fibre expression in the pons, and that IHH exposure does not prevent the nicotine-induced increase. Thus, although both nicotine and IHH are risk factors for SIDS, it appears they have opposing effects on OxA and OxB expression, with the IHH exposure closely mimicking what we recently found in SIDS.