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Summary: We present a case of a 55‐year‐old woman presenting for an elective minor procedure. Following a previous anaesthetic, a 'can't intubate, can't oxygenate' incident had been documented. She had since undergone awake tracheal intubation for procedures requiring general anaesthesia. We were able to safely facilitate awake tracheal intubation using remimazolam for sedation. Remimazolam is a novel ultra‐short acting benzodiazepine with similar pharmacodynamic effects to its parent compound midazolam, having minimal cardiovascular or respiratory effects and offering excellent anxiolysis and amnesia. It has a significantly shorter duration of action than midazolam, making it a valuable sedative agent for awake tracheal intubation. The patient remained stable throughout the procedure, with minimal effects on the respiratory and cardiovascular systems. The quality of sedation was reported as highly satisfactory by both the patient and the team. [ABSTRACT FROM AUTHOR]

Autophagy plays a vital role in cell homeostasis by eliminating nonfunctional components and promoting cell survival. Here, we examined the levels of autophagy signaling proteins after 7 days of overload hypertrophy in the extensor digitorum longus (EDL) and soleus muscles of control and diabetic rats. We compared control and 3‐day streptozotocin‐induced diabetic rats, an experimental model for type 1 diabetes mellitus (T1DM). EDL muscles showed increased levels of basal autophagy signaling proteins. The diabetic state did not affect the extent of overload‐induced hypertrophy or the levels of autophagy signaling proteins (p‐ULK1, Beclin‐1, Atg5, Atg12‐5, Atg7, Atg3, LC3‐I and II, and p62) in either muscle. The p‐ULK‐1, Beclin‐1, and p62 protein expression levels were higher in the EDL muscle than in the soleus before the hypertrophic stimulus. On the contrary, the soleus muscle exhibited increased autophagic signaling after overload‐induced hypertrophy, with increases in Beclin‐1, Atg5, Atg12‐5, Atg7, Atg3, and LC3‐I expression in the control and diabetic groups, in addition to p‐ULK‐1 in the control groups. After hypertrophy, Beclin‐1 and Atg5 levels increased in the EDL muscle of both groups, while p‐ULK1 and LC3‐I increased in the control group. In conclusion, the baseline EDL muscle exhibited higher autophagy than the soleus muscle. Although TDM1 promotes skeletal muscle mass loss and strength reduction, it did not significantly alter the extent of overload‐induced hypertrophy and autophagy signaling proteins in EDL and soleus muscles, with the two groups exhibiting different patterns of autophagy activation. [ABSTRACT FROM AUTHOR]

The authors discuss the need to assess the inability to reduce or discontinue opioids when benefits do not outweigh harms in patients on long-term opioid therapy for pain (LTOT). Topics include two forms of substance use disorders (SUD) contained in previous editions of the Diagnostic and Statistical Manual of Mental Disorders (DSM), how clinicians and patients can determine the harms and benefits LTOT for chronic pain, and the use of the term "substance use disorder" according to the DSM-5.

Warm (several eV to 100 eV) ions are an important, and still poorly understood, component of the magnetospheric plasma environment. We present the first comprehensive statistical analysis of several distinct populations of warm ions in the dayside middle and outer magnetosphere. We analyze 7 months (1 September 2015–31 March 2016) of Magnetospheric Multiscale Hot Plasma Composition Analyzer data comprising 734,200 moments (density, temperature) and energy‐dependent pitch angle distributions (PADs) of three major ion species (H+, He+, and O+) with energy ≤100 eV. PADs are represented by an energy‐averaged index that characterizes the shape of the PAD as field‐aligned (FA), pancake, or isotropic. We use filtering by temperature, pitch angle, and concentration to distinguish different populations, and obtain new and more complete information about average density, temperature, PADs, and composition. Our analysis explores two known populations of warm ions: the warm plasmasphere (WPS) and the warm cloak/trough (C/T). The WPS is a higher‐temperature, higher‐L extension of the duskside plasmaspheric bulge, containing mostly trapped (pancake/isotropic) ions with an H+:He+:O+ order of ion dominance. The C/T contains mostly FA warm ions with a dawnward (duskward) temperature gradient for H+ (He+ and O+), lower densities, and an H+:O+:He+ order of ion dominance. The WPS‐C/T overlap contains a mixture of the two populations (e.g., FA He+ in WPS, trapped O+ in C/T). Pancake (FA) PADs are correlated with higher (lower) density/temperature. Our analysis also identifies warm ions in the low‐energy plasma sheet. Our work consolidates and systematically extends the characterizations of warm ions reported in previous studies. Plain Language Summary: The plasmasphere is often defined as the cold and dense innermost region of the magnetosphere. The ring current may be defined as the torus of hot ions encircling the planet at several Earth radii of geocentric distance. Warm plasma (several eV to 100 eV) is an intermediate‐energy population. In this paper, we present the first comprehensive statistical analysis of several distinct populations of warm ions in the dayside middle and outer magnetosphere. We analyze 7 months (1 September 2015–31 March 2016) of data from the Magnetospheric Multiscale mission. Several‐eV to 100‐eV ions constitute a large reservoir of mass and momentum that can influence numerous basic, system‐level aspects of the magnetosphere. Warm ions are also a "bridge population" whose intermediate‐energy dynamics reveal heating and energization processes that trap ions to enable plasmaspheric refilling and transform very cold, ionospheric‐origin plasma into an integral component of the stormtime plasma sheet and ring current. Key Points: Statistical analysis of dayside warm (≤100 eV) ions uses 734,200‐point database of density, temperature, and pitch angle (PA) distributionsFiltering by temperature, PA, and concentration helps distinguish and separate different warm ion populationsThis analysis consolidates and systematically extends the characterizations of the warm plasmasphere and the warm cloak/trough (C/T) [ABSTRACT FROM AUTHOR]

In the past years studies were conducted on natural fibre reinforced polymer composites to observe their mechanical properties in order to decide their industrial applications. These composites have already been used in many applications from aerospace to sporting equipment. These green composites can be used as a replacement for synthetic composites. This is because the natural fibres are eco-friendly, biodegradable, renewable, etc. In this work, an attempt is made to reinforce fly ash, coir fibre and sugarcane fibre with epoxy polymer matrix. Central composite design under response surface methodology (RSM), one of the approaches of design of experiments (DOE) is used to determine optimum sample preparation conditions of fly ash, coir fibre and sugarcane fibre. Both tensile and flexural (three-point bending) tests are conducted on these fabricated composites to determine their materialistic characteristics. Analysis of variance (ANOVA) is carried out using Minitab software to find the influence of fly ash, coir fibre, sugarcane fibre on composites. Regression equations obtained from analysis of variance is used to calculate values. Experimental and calculated values are compared and their error % are calculated and tabulated. Response surface optimization study is carried to find the optimized parameters of composites. It is observed that, increase in wt.% of coir fibre and decrease in wt.% of fly ash and sugarcane fibre, increases yield stress and these parameters have mixed impact on ultimate tensile stress. The addition of fly ash, coir fibre and sugarcane fibre in low percentages increases Young’s modulus. Increase in wt.% of fly ash and coir fibre and decrease in wt.% of sugarcane, increases flexural modulus and flexural stress. [ABSTRACT FROM AUTHOR]

Purpose: In response to the opioid crisis, opioid analgesic guidelines and prescribing limits have proliferated. The purpose of this narrative review is to examine evidence from studies evaluating the patient or public health impact of federal and state opioid analgesic prescribing guidelines and laws, describe gaps and challenges in current research, and highlight opportunities for improving future research. Methods: We focused on evidence from a literature review covering 2013 through 2019. We identified 30 studies evaluating opioid analgesic thresholds based on federal policies and guidelines, state laws, and Medicaid state plans that attempt to influence the course of patient care at or when the limit is exceeded (e.g., prior authorization). Results: Most studies evaluated changes in prescribing or dispensing patterns of opioid analgesics, largely finding decreases in prescribing after policy enactment. Fewer studies evaluated patient or public health outcomes beyond changes in prescribing and dispensing patterns; results were infrequently stratified by potentially important sociodemographic and clinical factors. No studies assessed the potential for adverse patient outcomes for which we have emerging evidence of harms. Conclusions: We describe knowledge gaps and propose opportunities for future research to sufficiently assess the potential impact and unintended consequences of opioid analgesic prescribing laws, regulations, guidelines, and policies. [ABSTRACT FROM AUTHOR]

Aim: To examine prevalence of mental health conditions and receipt of mental health care (MHC) by illicit lysergic acid diethylamide (LSD) use status (past‐year; lifetime without‐past‐year; never) among young adults. Design Cross‐sectional, annual survey data from 2015 to 2019 National Surveys on Drug Use and Health (NSDUH). Setting: United States. Participants: A total of 69 916 NSDUH participants ages 18 to 25. Measurements Outcomes included past‐year serious psychological distress (SPD), suicidal ideation, Diagnostic and Statistical Manual of Mental Disorders (DSM)‐IV major depressive episode (MDE), any mental illness, serious mental illness, receipt of mental health care (MHC, inpatient/outpatient or receipt of prescription medications), and number of days of being unable to work or attend normal activities because of mental health conditions. Findings Multivariable analyses found that compared with those who never used illicit LSD, adults with past‐year illicit LSD use had greater risk of suicidal ideation (adjusted risk ratio [ARR] = 1.2, 95% CI = 1.06–1.41), SPD (ARR = 1.2, 95% CI = 1.04–1.28), MDE (ARR = 1.3, 95% CI = 1.17–1.52), and any/serious mental illness (ARRs = 1.2–1.3, 95% CI = 1.02–1.41) and reported missing more days because of mental health conditions (adjusted incidence rate ratio = 1.6, 95% CI = 1.31–1.86). Lifetime (without past‐year) use showed similar, although less consistent, associations. Compared with those never using illicit LSD, adults with past‐year use were less likely to receive prescription medications for MHC (ARR = 0.7, 95% CI = 0.60–0.84) and to receive overall MHC (ARR = 0.7, 95% CI= 0.64–0.84). Compared with those using in the past‐year, adults with lifetime (without past‐year) use were more likely to receive prescription medications for MHC (ARR = 1.2, 95% CI = 1.01–1.46) and receive overall MHC (ARR = 1.2, 95% CI = 1.03–1.45). Conclusions: Young adults with past‐year illicit lysergic acid diethylamide use have elevated prevalence of mental health conditions and are less likely to receive prescription medications for mental health care and overall mental health care. Regardless of past‐year use status, young adults with lifetime illicit lysergic acid diethylamide use may benefit from mental illness prevention and interventions. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the effects of supplemental phytase with xylanase and β‐glucanase blend on the apparent digestibility coefficient (ADC) of gross energy and nutrients, including amino acids, minerals, and nitrogen (N) and phosphorus (P) balance in Nile tilapia, Oreochromis niloticus. Diets were elaborated either without enzyme supplementation (control) or supplemented with phytase (PHY), xylanase and β‐glucanase (XB) blend or a combination of phytase plus xylanase and β‐glucanase (PHY+XB) blend. Fish (n = 192; 60 ± 3.4 g) were fed with the experimental diets replicated four times. Compared with the control group, fish‐fed with the PHY+XB diet showed a higher ADC of gross energy and nutrients, including amino acids and minerals. Also, compared to control diet, digestible energy, digestible protein and available P contents were higher in fish‐fed diet PHY+XB by 1.63 MJ kg−1, 7.21 and 4.70 g kg−1 diet respectively. Compared to the control group, fish‐fed diet PHY+XB displayed lower total N and P loss of 17.51 and 10.09 g kg−1 of body weight gain (BWG) respectively. The study findings provided new insight into the nutritive value and ecofriendliness/sustainability of diets associated with exogenous enzymes for tilapia culture. [ABSTRACT FROM AUTHOR]

Recent attention has focused on the growing role of psychostimulants, such as methamphetamine in overdose deaths. Methamphetamine is an addictive and potent stimulant, and its use is associated with a range of physical and mental health harms, overdose, and mortality. Adding to the complexity of this resurgent methamphetamine threat is the reality that the increases in methamphetamine availability and harms are occurring in the midst of and intertwined with the ongoing opioid overdose crisis. Opioid involvement in psychostimulant‐involved overdose deaths increased from 34.5% of overdose deaths in 2010 to 53.5% in 2019—an increase of more than 50%. This latest evolution of the nation's overdose epidemic poses novel challenges for prevention, treatment, and harm reduction. This narrative review synthesizes what is known about changing patterns of methamphetamine use with and without opioids in the United States, other characteristics associated with methamphetamine use, the contributions of the changing illicit drug supply to use patterns and overdose risk, motivations for couse of methamphetamine and opioids, and awareness of exposure to opioids via the illicit methamphetamine supply. Finally, the review summarizes illustrative community and health system strategies and research opportunities to advance prevention, treatment, and harm reduction policies, programs, and practices. [ABSTRACT FROM AUTHOR]

Background: In 2020, early U.S. COVID‐19 testing sites offered diagnostic capacity to patients and were important sources of epidemiological data about the spread of the novel pandemic disease. However, little research has comprehensively described American testing sites' distribution by race/ethnicity and sought to identify any relation to known disparities in COVID‐19 outcomes. Methods: Locations of U.S. COVID‐19 testing sites were gathered from 16 April to 28 May 2020. Geographic testing disparities were evaluated with comparisons of the demographic makeup of zip codes around each testing site versus Monte Carlo simulations, aggregated to statewide and nationwide levels. State testing disparities were compared with statewide disparities in mortality observed one to 3 weeks later using multivariable regression, controlling for confounding disparities and characteristics. Results: Nationwide, COVID‐19 testing sites geographically overrepresented White residents on 7 May, underrepresented Hispanic residents on 16 April, 7 May and 28 May and overrepresented Black residents on 28 May compared with random distribution within counties, with new sites added over time exhibiting inconsistent disparities for Black and Hispanic populations. For every 1 percentage point increase in underrepresentation of Hispanic populations in zip codes with testing, mortality among the state's Hispanic population was 1.04 percentage points more over‐representative (SE = 0.415, p =.01). Conclusions: American testing sites were not distributed equitably by race during this analysis, often underrepresenting minority populations who bear a disproportionate burden of COVID‐19 cases and deaths. With an easy‐to‐implement measure of geographic disparity, these results provide empirical support for the consideration of access when distributing preventive resources. [ABSTRACT FROM AUTHOR]

Clays are understood to form the majority of fluid‐flow barriers in faulted reservoirs and numerous fault gouge and fault seal studies have quantified the volumes of smeared and abraded clays create fluid‐flow barriers along fault surfaces. However, clay‐related permeability adjacent to the fault surface, including in the fault damage zone, has largely been neglected. Previous studies have shown the morphology and distribution of unfaulted authigenic clays, and not just clay volume, exert a significant control on the magnitude of permeability. However, fault‐related studies have neither characterized deformed authigenic clays nor addressed their influence on fluid‐flow. In this study laboratory permeabilities of faulted, authigenic clay bearing sandstones sampled from the Otway basin (Australia) and the Orcadian basin (UK) present trends which; (a) do not correspond to expected patterns of fluid‐flow in faulted clay‐bearing sandstones and, (b) cannot be explained using published models of permeability related to changing clay volume. Microscopic analysis shows that faulting has disaggregated authigenic clays and, similarly to framework grain deformation, comminuted and sheared clay grains. However, instead of impeding fluid‐flow, analysis of pore networks (using mercury injection porosimetry) showed that faulting of authigenic clays has increased pore connectivity, contributing to increased magnitude of permeability and development of permeability anisotropy. Contrary to published results of faulting and fluid‐flow in impure sandstones, our results show that fault related processes involving the formation of clays in the fault zone can increase permeability and reduce the capillary threshold pressures of fault rocks relative to the unfaulted host rock. Plain Language Summary: Predictions of fluid leakage in geological reservoirs are essential for energy extraction (e.g., geothermal, hydrocarbons), development and maintenance of sustainable energy resources (e.g., carbon dioxide sequestration and nuclear waste storage). Reservoir‐bounding faults commonly form fluid‐flow barriers as the process of faulting breaks grains and smears clays along fault surfaces creating a seal. Therefore, the volume of clay in faulted rocks is an important parameter in relation to fault sealing capacity. Authigenic clays are minerals that commonly grow in spaces between grains, choking fluid pathways and reducing flow. In this study, microscopic analysis of two faulted sandstones containing authigenic minerals (chlorite and kaolinite) showed that faulting also breaks authigenic clay grains. However, instead of impeding fluid‐flow, laboratory measurements of faulted sandstones showed that deformation of authigenic minerals can influence flow direction and even increase the magnitude of fluid‐flow. Consequently, rather than representing fluid barriers, some faults may actually form important fluid draining structures. These novel results prompt questions about the robustness of parameters currently used to model fluid‐flow around faults and, with global need for sustainable energy demanding that we can safely store fluids in subsurface reservoirs, should motivate geologists to take a fresh look at fault seal analysis. Key Points: Tectonically deformed authigenic clays have been identified in faulted sandstonesThe morphology, aggregate structure and distribution of authigenic clay can contribute to increased permeability in faulted sandstonesIn contrast to accepted fault seal models, this study shows that clay‐rich fault zone rocks can be the locus of better fluid‐flow [ABSTRACT FROM AUTHOR]

Despite the conduct of general anaesthesia for caesarean section evolving over more than a century, contemporary clinical practice has been slow to adopt new methods, despite a sound evidence base to support them. Difficult and failed intubation in obstetric anaesthesia: an observational study of airway management and complications associated with general anaesthesia for caesarean section. Keywords: caesarean section; general anaesthesia; implementation science EN caesarean section general anaesthesia implementation science 448 451 4 03/04/21 20210401 NES 210401 "Come gather 'round people, wherever you roam, And admit that the waters around you have grown!" Induction opioids for caesarean section under general anaesthesia: a systematic review and meta-analysis of randomised controlled trials. [Extracted from the article]

Near‐surface wedges of massive ice commonly outline polygons in tundra lowlands, but such polygons have been difficult to identify on hillslopes because soil movement flattens the ridges and infills the troughs that form beside and above the ice wedges. Over the past three decades, the active layer has thickened near the western Arctic coast of Canada and consequent thawing of ice wedges has been detected by remote sensing for flat terrain but not, generally, on hillslopes. Annual field surveys (1996–2018) at the Illisarvik field site of thaw depth and ground surface elevation show the mean subsidence rate above hillslope ice wedges has been up to 32 mm a−1 since thaw depth reached the ice‐wedge tops in 2007. Annual mean ground temperatures at the site are about −3.0°C beneath late‐winter snow depths characteristic of the ice‐wedge troughs but about −5.3°C under conditions of the intervening polygons. The rate of thaw subsidence is high for natural, subaerial disturbances because meltwater from the ice wedges runs off downslope. The rate is constant, because the thickness of seasonally thawed ground above the ice wedges and the ice content of the ground remain the same while the troughs develop. Observations of changes in surface elevation in northern Banks Island between the late 1970s and 2019 show troughs on hillslopes where none was previously visible. Development of these troughs creates regional thermokarst landscapes, distinct from the widely recognized results of thawing relict glacier ice, that are now widespread over Canada's western Arctic coastlands. Recognition of ice‐wedge occurrence and accelerated thaw subsidence on hillslopes is important in the design of infrastructure proposed for construction in rolling permafrost terrain. [ABSTRACT FROM AUTHOR]

Aim: Atrial fibrillation (AF) is a common cardiac arrhythmia, and is associated with worsening quality of life and complications such as stroke. Previous work showed that 8% of patients develop new‐onset AF following colonic resection and highlighted factors that might predict the development of postoperative AF. The development of a new arrhythmia may have a negative effect on longer‐term quality of life as well as cancer survivorship. The aim of this study is to accurately quantify the incidence of AF following colorectal cancer surgery and to validate a model to predict its development. Method: The Atrial Fibrillation After Resection (AFAR) study will recruit 720 patients aged 65 or over undergoing resection of colorectal cancer with curative intent. The primary outcome is development of AF within 90 days of surgery. Assessment of cardiac rhythm will be performed using 24‐h Holter monitors at baseline, 30 and 90 days after surgery. An electrocardiogram (ECG) will be performed on the day of discharge. Baseline descriptors including model variables and quality of life will be recorded using EQ‐5D‐5L. The occurrence of complications and other key surgical outcomes will be recorded. An additional blood test for N‐terminal pro B‐type natriuretic peptide (NT‐proBNP) will be performed prior to surgery. Statistical analysis will validate a previously derived model and will test the incremental value of added variables such as NT‐proBNP. Finally, an exploratory analysis will assess whether changes in ECG measures between baseline and postoperative ECG can predict subsequent new‐onset AF. Conclusion: This study will provide data that may allow us to stratify the risk of developing AF following colorectal cancer surgery. This may inform screening or prophylactic approaches. [ABSTRACT FROM AUTHOR]

Background: Acute appendicitis is a common surgical emergency that is typically managed with laparoscopic appendicectomy in UK centres. A number of variables influence the cost of managing this condition. Our aim was to identify the major influencing factors in our centre by performing a cumulative cost analysis. Methods: We retrospectively analysed the costs associated with 99 cases of acute appendicitis managed with laparoscopic appendicectomy at Ninewells Hospital, Dundee, from January 2014 to February 2016. Costs were categorised according to blood tests, imaging, medications, operative costs and length of stay. Results: Our cohort included 66 males, 33 females and 28 paediatric cases. The total cost was £220030.52 with a mean of £2222.53 per patient. The factor with the greatest influence on overall cost was operative time (53.2%) followed by length of stay (39.2%). There was no cost difference between adults and children (p = 0.24) or males and females (p = 0.38). Mean cost in adults ≥50 years was greater than those <50 years (£2899.32 vs £2152.97, p = 0.008) and greater in those who underwent imaging as opposed to no imaging (£2789.53 vs £2010.65, p = 0.0001). For appendiceal stump technique, polymer clips were cheaper (£1844.70) than ligatures (£2380.11, p = 0.006). Conclusions: Operative time (53.2%) and length of stay (39.2%) had the greatest impact on the cost in our cohort. Older patients have a greater overall cost, and this is associated with increased utilisation of imaging. Further studies assessing the safety and feasibility of methods to reduce operative time and to investigate the safety of reducing length of stay are required. [ABSTRACT FROM AUTHOR]

B Methods: b The ACOPP regimen comprises doxorubicin 35 mg/m SP 2 sp and cyclophosphamide 650 mg/m SP 2 sp intravenous infusion day (D) 1, vincristine 1.4 mg/m SP 2 sp intravenous injection D8, oral procarbazine 100 mg/m SP 2 sp D1-7, prednisolone 40 mg/m SP 2 sp D1-14 and subcutaneous G-CSF D9-13. B Introduction: b Patients (pts) aged >=60 years comprise 20%-30% of classical Hodgkin lymphoma (cHL) diagnoses, but are significantly underrepresented in clinical trials and outcomes for this group have not improved in line with advances seen in younger counterparts. Whilst treatment in clinical trials should be considered optimal therapy, enrolment in this group remains challenging and the ACOPP regimen offers promising outcomes in a difficult to treat population. [Extracted from the article]

Background and Aims: Due to their small sample sizes, geographic specificity and limited examination of socio‐demographic characteristics, recent studies of methamphetamine use among people using heroin in the United States are limited in their ability to identify national and regional trends and to characterize populations at risk for using heroin and methamphetamine. This study aimed to examine trends and correlates of methamphetamine use among heroin treatment admissions in the United States. Design Longitudinal analysis of data from the 2008 to 2017 Treatment Episode Data Set. Descriptive statistics, trend analyses and multivariable logistic regression were used to examine characteristics associated with methamphetamine use among heroin treatment admissions. Setting: United States. Participants: Treatment admissions of people aged ≥ 12 years whose primary substance of use is heroin. Measurements Primary measurement was heroin treatment admissions involving methamphetamine. Secondary measurements were demographics of sex, age, race/ethnicity, US census region, living arrangement and employment status. Findings The percentage of primary heroin treatment admissions reporting methamphetamine use increased each year from 2.1% in 2008 to 12.4% in 2017, a relative percentage increase of 490% and an annual percentage change (APC) of 23.4% (P < 0.001). During the study period, increases were seen among males and females and among all demographic and geographic groups examined. Among primary heroin treatment admissions reporting methamphetamine use in 2017, 47.1% reported injecting, 46.0% reported smoking, 5.1% reporting snorting and 1.8% reported oral/other as their usual route of methamphetamine use. Conclusions: Methamphetamine use among heroin treatment admissions in the United States increased from one in 50 primary heroin treatment admissions in 2008 to one in 8 admissions in 2017. [ABSTRACT FROM AUTHOR]

The roots of the remarkably lethal U.S. opioid crisis are complex and inextricably entangled with healthcare, especially in its treatment of another serious health problem: pain. Failures of the healthcare system—including lack of both training in pain management and caution in using an addictive class of medications—precipitated the rise in opioid misuse and addiction over the past two decades, but a wider range of social and economic forces has helped perpetuate the crisis and altered its character. The classic epidemiologic host–agent–environment triad can be augmented for the purpose of elucidating the current opioid crisis by addition of the "vector" to emphasize the importance of purveyors of opioids (licit and illicit), leading to our proposing an expanded host–agent–vector–environment model. Interventions addressing multiple components are needed, including solutions that account for behaviors of all vectors associated with the crisis. For prescription opioids, the vectors include clinicians and pharmaceutical‐related companies involved in marketing, prescribing, distributing, and dispensing opioid medications; for illicit opioids, they include drug manufacturing and distribution networks. Attending to the vectors of opioids, while simultaneously implementing a full range of public health, clinical, law enforcement, and other approaches to ending the opioid crisis, may help to improve public health outcomes. [ABSTRACT FROM AUTHOR]

Sequential analysis hypothesis testing is now an important tool for postmarket drug and vaccine safety surveillance. When the number of adverse events accruing in time is assumed to follow a Poisson distribution, and if the baseline Poisson rate is assessed only with uncertainty, the conditional maximized sequential probability ratio test, CMaxSPRT, is a formal solution. CMaxSPRT is based on comparing monitored data with historical matched data, and it was primarily developed under a flat signaling threshold. This paper demonstrates that CMaxSPRT can be performed under nonflat thresholds too. We pose the discussion in the light of the alpha spending approach. In addition, we offer a rule of thumb for establishing the best shape of the signaling threshold in the sense of minimizing expected time to signal and expected sample size. An example involving surveillance for adverse events after influenza vaccination is used to illustrate the method. [ABSTRACT FROM AUTHOR]

Aim: This study estimated whether and how the 12‐month prevalence of cannabis use disorder among US youth aged 12–17 and emerging adults aged 18–25 varied by time since first cannabis use. Design Repeated cross‐sectional survey data from the 2015–17 National Surveys on Drug Use and Health (NSDUH). Setting: United States. Participants: A total of 101 000 NSDUH participants aged 12–25. Measurements: Past 12‐month cannabis use disorder was assessed using DSM‐IV criteria. Findings Among youth, the life‐time prevalence of cannabis use was 15.3% [95% confidence interval (CI) = 14.86–15.65%]. Among emerging adults, the life‐time prevalence of cannabis use was 52.4% (95% CI = 51.77–53.01%). The adjusted 12‐month prevalence of cannabis use disorder among youth with life‐time cannabis use was 10.9% (95% CI = 9.24–12.75%) in the first year after starting cannabis use, 15.3% (95% CI = 13.68–17.12%) in the second year, 17.7% (95% CI = 15.55–19.97%) in the third year and 20.6% (95% CI = 18.23–23.17%) in the fourth year and beyond, which was consistently higher after the first year (linear trend only: P < 0.0001). The adjusted 12‐month prevalence of cannabis use disorder among emerging adults with life‐time use ranged from 5.6% (95% CI = 4.26–7.23%) in the first year after starting cannabis use, 7.7% (95% CI = 6.45–9.17%) in the second year and 9.1% (95% CI = 7.81–10.57%) in the third year to 10.5% (95% CI = 9.87%–11.12%) in the fourth year and beyond, which was consistently higher after the first year (linear trend only: P < 0.0001). Within each time‐frame since first cannabis use, the adjusted 12‐month prevalence of cannabis use disorder was higher among youth life‐time users than their emerging adult counterparts. Conclusions: Among youth and emerging adults in the United States, the prevalence of cannabis use disorder appears to increase with time since initiation of use and is higher among youth than among emerging adults during each examined time‐frame. [ABSTRACT FROM AUTHOR]

Idiopathic non‐cirrhotic portal hypertension (INCPH) is a rare vascular liver disease that has attracted new interest in recent years. It is characterised by clinical signs of portal hypertension in the absence of cirrhosis or severe fibrosis and any known cause of portal hypertension. As much uncertainty exists about INCPH pathophysiology, and no definite diagnostic tests are available, liver biopsy is an essential tool for achieving a definite diagnosis. Unfortunately, the histological diagnosis of INCPH is not always straightforward, as the characteristic lesions are unevenly distributed, vary greatly in their severity, are often very subtle, and are not all necessarily present in a single case. Furthermore, specifically for the characteristic portal vessel changes observed in INCPH, the terminology and definition are ambiguous, which adds complexity to the already complex clinicopathological scenario. An international study group of liver pathologists and hepatologists pursued a consensus on nomenclature for the portal vascular lesions of INCPH. Such standardisation may assist pathologists in the recognition of such lesions, and will possibly facilitate further advancement in this field. [ABSTRACT FROM AUTHOR]

Summary: Background: Equine herpesvirus type 1 (EHV‐1) is the cause of respiratory disease, abortion storms, and outbreaks of herpesvirus myeloencephalopathy (EHM). Infection of the spinal cord is characterised by multifocal regions of virally infected vascular endothelium, associated with vasculitis, thrombosis and haemorrhage that result in ischaemia and organ dysfunction. However, the mechanism of thrombosis in affected horses is unknown. Objectives: To evaluate tissue factor (TF) procoagulant activity and thrombin–antithrombin complex (TAT) levels in horses following infection with EHV‐1. Study design: In vitro and in vivo studies following experimental EHV‐1 infection. Methods: Horses were infected with EHV‐1 and levels of peripheral blood mononuclear cell (PBMC)‐associated TF activity; plasma and cerebrospinal fluid (CSF)‐derived microvesicle (MV)‐associated TF activity and TAT complexes in plasma were examined. Results: EHV‐1 infection increased PBMC TF procoagulant activity in vitro and in vivo. In infected horses, this increase was observed during the acute infection and was most marked at the onset and end of viraemia. However, no significant differences were observed between the horses that showed signs of EHM and the horses that did not develop EHM. Significant changes in MV‐associated TF procoagulant activity and TAT complexes were not observed in infected horses. Main limitations: A small number of horses typically exhibit clinical EHM following experimental infection. Conclusions: The results indicate that EHV‐1 infection increases PBMC‐associated TF procoagulant activity in vivo and in vitro. Additional in vivo studies are needed to better understand the role of TF‐dependent coagulation during EHM pathogenesis in horses. [ABSTRACT FROM AUTHOR]

Purpose: To assess the overdiagnosis of open‐angle glaucoma (OAG) and to investigate associated factors. Methods: This was a cross‐sectional, population‐based study of an urban Caucasian population in northern Greece. Randomly selected subjects ≥60 years (n = 2554) participated in the Thessaloniki Eye Study. The definition of OAG required the presence of structural and functional damage, irrespective of intraocular pressure (IOP). Non‐OAG subjects were classified as overdiagnosed with OAG if they had reported at least one of the following (self‐reported glaucoma): (i) prior diagnosis of glaucoma, (ii) prior laser for glaucoma, (iii) prior glaucoma surgery. Factors associated with the overdiagnosis of OAG were investigated using a logistic regression model. Results: Of 57 (2.2%) subjects with self‐reported glaucoma, 34 (60%) were overdiagnosed with OAG, corresponding to a prevalence of 1.3% (34/2554). In a logistic regression model among non‐OAG subjects, worse visual acuity (VA) (20/200 or worse versus 20/25 or better; odds ratio (OR) = 4.30, 95% Confidence Intervals (CI), 1.13–16.35), family history of glaucoma (OR = 8.69, 95% CI, 2.83–26.67) and history of cataract surgery (OR = 11.50, 95% CI, 3.85–34.36) were statistically significantly associated with the overdiagnosis of OAG. Age, sex, higher IOP, higher vertical cup‐to‐disc ratio and pseudoexfoliation were not statistically significant. Conclusion: The overdiagnosis of OAG was substantial in this elderly, Caucasian population. The overdiagnosis of glaucoma has not been previously addressed in population‐based studies and needs to be further explored. [ABSTRACT FROM AUTHOR]

Abstract: Aim: Pseudomyxoma peritonei (PMP) is a rare neoplasm of the appendix, which if untreated disseminates throughout the abdominal cavity and generates considerable morbidity. Since 2002 in the UK, patients with PMP have been managed via two nationally commissioned centres. We evaluated referrals and treatment pathways over time at the Manchester centre. Method: Data from all patients referred with suspected PMP were prospectively collected (2002–2015). Definitive treatment was cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy. Disease burden was quantified using the Peritoneal Cancer Index (PCI) (score 0–39) and complete cytoreduction (CC) defined by scores of 0/1. Novel treatment algorithms were developed for patients with low grade appendiceal mucinous neoplasm (LAMN) localized to the peri‐appendiceal tissue. Results: In all, 817 patients with confirmed PMP were referred increasing from 11 in 2002 to 103 in 2015. Disease burden was high with a mean PCI of 31 in the first quartile (Q1), levelling off to 15, 15, 17 thereafter (P = 0.002). The proportion of CC0/1 increased from 67% in Q1 to 77% Q2 and 74% Q3/4. Where complete cytoreduction was achieved, 5‐ and 10‐year overall survival was 77% and 66%. The proportion of patients referred with localized LAMN increased over time reaching 25% each year since 2010 (Ptrend < 0.0001). Two‐thirds of localized LAMN now undergo laparoscopically assisted risk‐reducing CRS. Conclusion: The establishment of a national treatment centre was associated with an initial presentation of patients with advanced disease. The programme has demonstrated a clear trend over time towards earlier referral and adoption of minimally invasive techniques for localized disease. [ABSTRACT FROM AUTHOR]

Abstract: Background: Primary chronic intestinal pseudo‐obstruction (CIPO) is a rare, potentially life‐threatening disorder characterized by severely impaired gastrointestinal motility. The objective of this study was to examine the contribution of ACTG2, LMOD1, MYH11, and MYLK mutations in an Australasian cohort of patients with a diagnosis of primary CIPO associated with visceral myopathy. Methods: Pediatric and adult patients with primary CIPO and suspected visceral myopathy were recruited from across Australia and New Zealand. Sanger sequencing of the genes encoding enteric gamma‐actin (ACTG2) and smooth muscle leiomodin (LMOD1) was performed on DNA from patients, and their relatives, where available. MYH11 and MYLK were screened by next‐generation sequencing. Key results: We identified heterozygous missense variants in ACTG2 in 7 of 17 families (~41%) diagnosed with CIPO and its associated conditions. We also identified a previously unpublished missense mutation (c.443C>T, p.Arg148Leu) in one family. One case presented with megacystis‐microcolon‐intestinal hypoperistalsis syndrome in utero with subsequent termination of pregnancy at 28 weeks' gestation. All of the substitutions identified occurred at arginine residues. No likely pathogenic variants in LMOD1, MYH11, or MYLK were identified within our cohort. Conclusions and inferences: ACTG2 mutations represent a significant underlying cause of primary CIPO with visceral myopathy and associated phenotypes in Australasian patients. Thus, ACTG2 sequencing should be considered in cases presenting with hypoperistalsis phenotypes with suspected visceral myopathy. It is likely that variants in other genes encoding enteric smooth muscle contractile proteins will contribute further to the genetic heterogeneity of hypoperistalsis phenotypes. [ABSTRACT FROM AUTHOR]

Atrial fibrillation is a common cardiac arrhythmia and can occur de novo following a surgical procedure. It is associated with increased inpatient and long-term mortality. There is limited evidence concerning new-onset atrial fibrillation following abdominal surgery. This study aimed to identify the prevalence of and risk factors for postoperative atrial fibrillation in the general surgical population. A systematic search of the Embase, MEDLINE and Cochrane (CENTRAL) databases was conducted. Studies were included in the review if they reported cases of new-onset atrial fibrillation within 30 days of the index operation. Results were evaluated qualitatively due to substantial clinical heterogeneity. Incidence rates were pooled using a weighted random-effects meta-analysis model. A total of 835 records were initially identified, from which 32 full texts were retrieved. Following review, 13 studies were included that involved 52,959 patients, of whom 10.94% (95%CI 7.22-15.33) developed atrial fibrillation. Five studies of patients undergoing oesophagectomy (n = 376/1923) had a weighted average rate of 17.66% (95%CI 12.16-21.47), compared with 7.63% (95%CI 4.39-11.98) from eight studies of non-oesophageal surgery (n = 2927/51,036). Identified risk factors included: increasing age; history of cardiac disease; postoperative complications, particularly, sepsis, pneumonia and pleural effusions. New-onset postoperative atrial fibrillation is common, and is more frequent after surgery involving the thorax. Future work should focus on stratifying risk to allow targeted prophylaxis of atrial fibrillation and other peri-operative complications. [ABSTRACT FROM AUTHOR]

Abstract: For the sake of rigorous control of task variables, hippocampal place cells have been usually studied in relatively simple environments. To approach the situation of real‐life navigation in an urban‐like environment, we recorded CA1 place cells while rats performance a memory task in a “Townmaze” with two start locations, three alternate paths in the maze midsection, followed by a two‐way choice that determined the trial outcome, access to a goal compartment. Further, to test the ability of place cells to update their spatial representation upon local changes in the environment while maintaining the integrity of the overall spatial map to allow effective navigation, we occasionally introduced barriers in the maze mid‐section to force the rat to select a nonpreferred route. The “Townmaze” revealed many new interesting features of CA1 neurons. First, we found neurons with 3–5 fields that appear to represent segments on a single common route through the maze. Second, we found neurons with 3–5 fields similarly aligned along the longitudinal or transverse maze axis. Responses to the barriers were assessed separately near and far from the barriers. Appearance of new fields in response to the barriers took place almost exclusively only locally near the barrier, whereas in‐field firing rate changes occurred throughout the maze. Further, field location changes did not correlate with the task performance, whereas firing rate changes did. These findings suggest that in a complex environment with blocked distal views, CA1 neurons code for the environment as sequences of significant nodes but are also capable of extracting and associating common elements across these sequences. [ABSTRACT FROM AUTHOR]

The origin of chalcocite is explored through a comparison of the copper isotope values of this mineral from supergene enrichment, sedimentary copper/red bed, and high-temperature hypogene mineralization around the world. Data from the literature and the data presented here (n=361) reveal that chalcocite from high-temperature mineralization has the tightest cluster of values of δCu65=0±0.6 in comparison to sedimentary copper/red bed δCu65=-0.9±1.0 and supergene enrichment δCu65=+1.9±1.8. Although the errors of the means overlap, large portions of the data lie in different values, allowing for distinguishing ranges for δCu65 of <−1‰ for sedimentary copper/red bed, between -1 and +1 for high-temperature hypogene, and >+1 for supergene enrichment chalcocite. The copper isotope values of sedimentary copper/red bed and supergene enrichment chalcocite are caused by redox reactions associated with the dissolution and transport of copper, whereas the tighter range of copper isotope values for hypogene minerals is associated with processes active with equilibrium conditions. [ABSTRACT FROM AUTHOR]

Groundwater flow resulting from a proposed hydraulic fracturing (fracking) operation was numerically modeled using 91 scenarios. Scenarios were chosen to be a combination of hydrogeological factors that a priori would control the long-term migration of fracking fluids to the shallow subsurface. These factors were induced fracture extent, cross-basin groundwater flow, deep low hydraulic conductivity strata, deep high hydraulic conductivity strata, fault hydraulic conductivity, and overpressure. The study considered the Bowland Basin, northwest England, with fracking of the Bowland Shale at ~2,000 m depth and the shallow aquifer being the Sherwood Sandstone at ~300-500 m depth. Of the 91 scenarios, 73 scenarios resulted in tracked particles not reaching the shallow aquifer within 10,000 years and 18 resulted in travel times less than 10,000 years. Four factors proved to have a statistically significant impact on reducing travel time to the aquifer: increased induced fracture extent, absence of deep high hydraulic conductivity strata, relatively low fault hydraulic conductivity, and magnitude of overpressure. Modeling suggests that high hydraulic conductivity formations can be more effective barriers to vertical flow than low hydraulic conductivity formations. Furthermore, low hydraulic conductivity faults can result in subsurface pressure compartmentalization, reducing horizontal groundwater flow, and encouraging vertical fluid migration. The modeled worst-case scenario, using unlikely geology and induced fracture lengths, maximum values for strata hydraulic conductivity and with conservative tracer behavior had a particle travel time of 130 years to the base of the shallow aquifer. This study has identified hydrogeological factors which lead to aquifer vulnerability from shale exploitation. [ABSTRACT FROM AUTHOR]

Lipid bodies ( LBs) are intracellular accumulations of neutral lipids surrounded by a single membrane. These organelles are involved in the production of eicosanoids, which modulate immunity by either promoting or dampening inflammatory responses. Leishmania infantum, the etiological agent of visceral leishmaniasis in Brazil, is an intracellular parasite that causes disease by suppressing macrophage microbicidal responses. C57 BL/6 mouse bone marrow-derived macrophages infected with L. infantum strain LcJ had higher numbers of LB+ cells ( P<.0001) and total LBs than noninfected cultures. Large (>3 μm) LBs were present inside parasitophorous vacuoles ( PVs). These results contrast with those of L. infantum-infected BALB/c macrophages, in which the only LBs are derived from parasite, not macrophage origin. Increased LBs in C57 BL/6 macrophages in close association with parasites would position host LBs where they could modulate L. infantum infection. These results imply a potential influence of the host genetics on the role of LBs in host-pathogen interactions. Overall, our data support a model in which the expression, and the role of LBs upon infection, ultimately depends on the specific combination of host-pathogen interactions. [ABSTRACT FROM AUTHOR]

Intestinal helminth infections are highly prevalent in the developing world, often resulting in chronic infection and inflicting high host morbidity. With the emergence of drug-resistant parasites, a limited number of chemotherapeutic drugs available and stalling vaccine efforts, an increased understanding of antihelminth immunity is essential to provide new avenues to therapeutic intervention. Micro RNAs are a class of small, nonprotein coding RNAs which negatively regulate mRNA translation, thus providing finite control over gene expression in a plethora of biological settings. The mi RNA-mediated coordinated control of gene expression has been shown to be essential in infection and immunity, in promoting and fine-tuning the appropriate immune response. This review gathers together and discusses observations of mi RNA-mediated effects on the immune system and the subsequent impact on our understanding of antihelminth immunity. [ABSTRACT FROM AUTHOR]

Quiet eye training (QET) may be a more effective method for teaching children to catch than traditional training (TT) methods, but it is unclear if the benefits accrued persist in the long term. Thirty children were randomly allocated into a QET or TT group and, while wearing a mobile eye tracker, underwent baseline testing, training and two retention tests over a period of eight weeks, using a validated throw and catch task. During training, movement-related information was provided to both groups, while the QET group received additional instruction to increase the duration of their targeting fixation (QE1) on the wall prior to the throw, and pursuit tracking (QE2) period on the ball prior to catching. In both immediate (R1) and delayed (R2, six weeks later) retention tests, the QET group had a significantly longer QE1 duration and an earlier and longer QE2 duration, compared to the TT group, who revealed no improvements. A performance advantage was also found for the QET compared to the TT group at both R1 and R2, revealing the relatively robust nature of the visuomotor alterations. Regression analyses suggested that only the duration of QE1 predicted variance in catch success post-training, pointing to the importance of a pre-programming visuomotor strategy for successful throw and catch performance. [ABSTRACT FROM PUBLISHER]

Background Hydrogen sulfide (H2S) serves as a mammalian cell-derived gaseous neurotransmitter. The intestines are exposed to a second source of this gas by sulfate-reducing bacteria ( SRB). Bismuth subsalicylate binds H2S rendering it insoluble. The aim of this study was to test the hypothesis that SRB may slow intestinal transit in a bismuth-reversible fashion. Methods Eighty mice were randomized to five groups consisting of Live SRB, Killed SRB, SRB+Bismuth, Bismuth, and Saline. Desulfovibrio vulgaris, a common strain of SRB, was administered by gavage at the dose of 1.0 × 109 cells along with rhodamine, a fluorescent dye. Intestinal transit was measured 50 minutes after gavage by euthanizing the animals, removing the small intestine between the pyloric sphincter and the ileocecal valve and visualizing the distribution of rhodamine across the intestine using an imaging system ( IVIS, Perkin-Elmer). Intestinal transit (n=50) was compared using geometric center (1=minimal movement, 100=maximal movement). H2S concentration (n=30) was also measured when small intestinal luminal content was allowed to generate this gas. Key Results The Live SRB group had slower intestinal transit as represented by a geometric center score of 40.2 ± 5.7 when compared to Saline: 73.6 ± 5.7, Killed SRB: 77.9 ± 6.9, SRB+Bismuth: 81.0 ± 2.0, and Bismuth: 73.3 ± 4.2 ( P<.0001). Correspondingly, the Live SRB group had the highest luminal H2S concentration of 4181.0 ± 968.0 ppb compared to 0 ± 0 ppb for the SRB+Bismuth group ( P<.0001). Conclusions & Inferences Live SRB slow intestinal transit in a bismuth-reversible fashion in mice. Our results demonstrate that intestinal transit is slowed by SRB and this effect could be abolished by H2S-binding bismuth. [ABSTRACT FROM AUTHOR]

Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID), also known for its significant antipyretic and analgesic properties. This chiral drug is commercialized in racemic form; however, only S-(+)-ibuprofen has clinical activities. In this paper the effect of temperature change (from 288.15 to 308.15 K) on the ibuprofen resolution was studied. A column (250×4.6 mm) packed with tris(3,5-dimethylphenylcarbamate) was used to obtain the thermodynamic parameters, such as enthalpy change (ΔH), entropy change (ΔS), variation enthalpy change (ΔΔH), variation entropy change (ΔΔS), and isoenantioselective temperature (Tiso). The mobile phase was a combination of hexane (99%), isopropyl alcohol (1%), and TFA (0.1%), as an additive. The conditions led to a selectivity of 1.20 and resolution of 4.55. The first peak, R-(−)-ibuprofen, presented an enthalpy change of 7.21 kJ/mol and entropy change of 42.88 kJ/K·mol; the last peak, S-(+)-ibuprofen, has an enthalpy change of 8.76 kJ/mol and 49.40 kJ/K·mol of entropy change. [ABSTRACT FROM AUTHOR]

The phytoplasmas of groups 16SrI (' Candidatus Phytoplasma asteris') and 16Sr VII (' Ca. Phytoplasma fraxini') have been associated with phytoplasma diseases in several urban tree species in Bogotá, Colombia and surrounding areas. The insect vectors responsible for this phytoplasma transmission are unknown. The objectives of this study were to test for the presence of phytoplasmas in leafhopper species (Cicadellidae) collected in areas with diseased trees and to determine the phytoplasma transmission ability of two of these species. Leafhoppers of nine species were collected at two sampling sites and tested by nested or double nested PCR using primers for the 16S rRNA gene. The amplicons were subjected to RFLP and/or sequencing analysis. Phytoplasmas of group 16SrI were detected in morphospecies MF05 ( Haldorus sp.), group 16Sr VII in MF07 ( Xestocephalus desertorum), MF08 ( Empoasca sp.) and MF09 (Typhlocybinae), and both groups 16SrI and 16Sr VII in MF01 ( Empoasca sp.), MF02 (Typhlocybinae), MF03 ( Scaphytopius sp.), MF04 ( Amplicephalus funzaensis) and MF06 ( Exitianus atratus). Transmission tests to uninfected bean plants ( Phaseolus vulgaris) were performed using field collected A. funzaensis and E. atratus individuals in separate assays. After 5 weeks, the test plants exposed to individuals of both species of leafhoppers showed symptoms, suggesting phytoplasma infection. Phytoplasma groups 16SrI and 16Sr VII were detected in the two groups of exposed plants, indicating that A. funzaensis and E. atratus were able to transmit both groups of phytoplasmas. This is the first report of insect vectors for phytoplasmas of group 16Sr VII in the world and of 16SrI in South America. [ABSTRACT FROM AUTHOR]

Clinicopathological concepts on acute and chronic liver disease have evolved rapidly during the last few years, with advances in general and specific treatment options and improved patient outcomes. The old paradigm of 'irreversibility' of cirrhosis had been challenged in major ways, and the validity of the usage of the term 'cirrhosis' has come into question. This paper addresses aetiology-based clinicopathological concepts and features that may deserve attention because they may determine disease outcome and, specifically, patterns of regression and remodelling. A variety of therapeutic interventions may influence remaining disease features after elimination of damaging agents (virus, alcohol, etc.), and determine the final clinical outcome including the risk of hepatocellular carcinoma ( HCC). New concepts create new responsibilities and opportunities for the pathologist to contribute to the understanding of liver pathology and communicate this with clinical colleagues and researchers. [ABSTRACT FROM AUTHOR]

Aim To fabricate a keratin hydrogel, characterize its functionality as a biomaterial and investigate the effects of keratin on growth and differentiation of odontoblast-like cells. Methodology Keratins were extracted from sheep wool using a well-established technique. The extracted proteins were purified by dialysis, quantified by gel electrophoresis, mass spectrometry, amino acid analysis and inductively coupled mass spectrometry. The microstructure of the fabricated keratin hydrogels was studied by scanning electron microscopy, flow characteristics by rheometer, hydrolytic stability and cytocompatibility by Live/Dead® cell assay. Furthermore, the influence of keratin on odontoblast-like cells (MDPC-23) was assessed to confirm their bioactivity at different dilutions. Cell proliferation was studied using alamarBlue® assay and differentiation by alkaline phosphatase enzyme activity, alizarin red staining and calcium quantification, reverse transcription polymerase chain reaction (rt-PCR) and immunocytochemical staining for dentine matrix protein- 1 (DMP-1) expression. anova with Tukey's tests was performed for statistical comparison. Results The characterized hydrogel was injectable with a highly porous architecture that underwent slow degradation, and its cytocompatibility was statistically equivalent to collagen hydrogel ( P > 0.05). Cell proliferation and differentiation were enhanced at the optimal keratin concentration of 0.1 mg mL−1. At this concentration, the influence of keratin on cell differentiation was demonstrated by marked elevation in alkaline phosphatase activity ( P < 0.05), calcium deposition ( P < 0.01), gene expression ( P < 0.01) and positive immunostaining for DMP-1. Conclusion The presence of keratin enhanced odontoblast cell behaviour. Keratin hydrogels may be a potential scaffold for pulp-dentine regen-eration. [ABSTRACT FROM AUTHOR]

Larval therapy, the therapeutic use of blowfly larvae to treat chronic wounds, is primarily used in debridement. There are, however, gaps in current knowledge of the optimal clinical application of the therapy and mechanisms of action in the debridement process. Using an artificial assay, two studies were undertaken to investigate these aspects of larval debridement by Lucilia sericata Meigen (Diptera: Calliphoridae); the first studied the effects of the density of larvae on tissue digestion and larval mass, and the second considered the effects on the same parameters of incorporating protease inhibitors into the feeding substrate. The total mass of tissue digested increased with larval density until saturation was observed at 5.0-7.5 larvae/cm2. This range was considered optimal as lower doses resulted in the removal of less tissue and higher doses offered no additional tissue removal and appeared to exacerbate competition for feeding. In the second study, increased protease inhibitor concentration led to significant decreases in tissue digestion and larval mass, suggesting that serine proteases, particularly trypsin, may play major roles in larval digestion. Such information is important in elucidating the main constituents that make up larval digestive products and may be significant in the development of new therapies. [ABSTRACT FROM AUTHOR]

Summary: An 18‐year‐old man underwent surgery for correction of idiopathic scoliosis. Due to the requirement for intra‐operative spinal cord monitoring, propofol and remifentanil total intravenous anaesthesia was chosen as the anaesthetic technique. Clonidine was given intra‐operatively as part of his analgesic regimen. No long‐acting opioids were administered. There was delayed emergence after switching off total intravenous anaesthesia and he remained sedated with a bispectral index of approximately 60 for 90 min. The common causes of delayed emergence were excluded. Shortly after administering naloxone, there was an increase in bispectral index and emergence from anaesthesia. We describe the successful use of naloxone to reverse the sedation effects of clonidine. [ABSTRACT FROM AUTHOR]

Objective: To determine whether pregnancy status, gynaecological history, date of last menstrual period and contraceptive use are documented in emergency female admissions of reproductive age admitted to general surgery. Design: This is a retrospective study. Setting: This study was conducted in the United Kingdom. Population: Females of reproductive age (12-50 years) admitted as an emergency to general surgery with abdominal pain were considered in this study. Methods: Retrospective analysis of medical notes of emergency female admissions with abdominal pain between January and September 2012. We recorded whether a pregnancy test result was documented (cycle 1). Results were analysed and a prompt added to the medical clerk-in document. We re-audited (cycle 2) between January and June 2013 looking for improvement. Main outcome measures: Documented pregnancy status within 24 h of admission and prior to any surgical intervention. Results: 100 case notes were reviewed in stage 1. 30 patients (30 %) had a documented pregnancy status. 32 (32 %), 25 (25 %) and 29 (29 %) had a documented gynaecology history, contraceptive use and date of last menstrual period (LMP), respectively. 24 patients underwent emergency surgery, 6 (25 %) had a documented pregnancy status prior to surgery. Of 50 patients reviewed in stage 2, 37 (75.0 %) had a documented pregnancy status ( p < 0.001), with 41 (82 %) having both gynaecological history ( p < 0.0001) and contraceptive use ( p < 0.0001) documented. 40 patients (80 % had a documented LMP ( p < 0.0001). 7 patients required surgery, of whom 6 (85.7 %) had a documented pregnancy test prior to surgery ( p = 0.001). All pregnancy tests were negative. Conclusions: A simple prompt in the surgical admission document has significantly improved the documentation of pregnancy status and gynaecological history in our female patients, particularly in those who require surgical intervention. A number of patient safety concerns were addressed locally, but require a coordinated, interdisciplinary discussion and a national guideline. A minimum standard of care, in females of reproductive age, should include mandatory objective documentation of pregnancy status, whether or not they require surgical intervention. [ABSTRACT FROM AUTHOR]

The article presents a study which aims to train doctors in collaborative and ethical communication regarding informed consent and assess the impact of training on the behaviour, stress and satisfaction of a physician. It shows that doctors strongly supported the training and did not demonstrate reduced stress and burnout. Results suggest the potential of training to improve a number of aspects of obtaining informed consent.

Government has funded a programme of nutrient analysis of foods for many decades and resulting data have been published in successive editions of M c C ance and W iddowson's The Composition of Foods. Latest data were published in the seventh summary edition of The Composition of Foods in 2014 and in a revised Composition of Foods Integrated Dataset in 2015. The main purpose of the nutrient analysis programme is to provide data to support estimation of nutrient intakes in the National Diet and Nutrition Survey and other dietary surveys. Changes in the nutrient content of the UK food supply over time are driven by a number of factors including reformulation of processed foods resulting from policies to improve public health. Up-to-date nutrient composition data are key to ensuring that estimates of nutrient intakes in UK dietary surveys remain robust. [ABSTRACT FROM AUTHOR]

In rehydroxylation (RHX) dating, the activation energy of the rehydroxylation reaction is required first in the estimate of a material's effective lifetime temperature (ELT), and second to correct the RHX rate constant obtained at a given measurement temperature to that at the ELT. Measurement of the activation energy is thus integral to the RHX methodology. In this paper, we report a temperature-step method for the measurement of activation energy and develop fully the underlying theoretical basis. In contrast to obtaining the activation energy from a series of separate experiments (each of which requires the sample to be dehydroxylated prior to measuring the RHX rate constant), the temperature-step method not only requires a single dehydroxylation at 500°C but also eliminates repeated acquisition of Stage I data, which are not required for dating purposes. Since the first temperature step is set to correspond to the temperature at which a dating determination is carried out, the measurement of rate constants at higher temperatures simply becomes an extension of dating. Consequently, the logistics of obtaining the activation energy of rehydroxylation are greatly simplified. [ABSTRACT FROM AUTHOR]