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Background Being able to function cognitively is imperative for successful achievement in school, working life, and disease self-management. Diabetes is known to cause changes in brain structure and long-term cognitive dysfunction. This work investigated cystic fibrosis-related diabetes (CFRD) as a mechanism for cognitive impairment in people with CF. It was hypothesised that cognition would be poorer in adults with CFRD than in those with CF without diabetes (CFND) or in healthy controls. Methods Cognitive performance was assessed using the Cambridge Neuropsychological Test Automated Battery which provides a comprehensive cognitive assessment with tests mapping onto specific brain regions. Demographic, clinical and self-reported health data were documented for all participants. CF specific clinical variables were recorded for the two CF groups. Results Ninety-eight people with CF (49CFRD,49CFND) and 49 healthy controls were recruited. People with CF demonstrated deficits in aspects of verbal and spatial memory, processing speed and cognitive flexibility compared with healthy controls, with all areas of the brain implicated. Those with CFRD had additional difficulties with higher-level processes known collectively as ‘executive function’, which demand greater cognitive load and recruit the prefrontal cortex. Compared with healthy controls, those with CFND and CFRD had an estimated 20% and up to 40% reduction in processing speed respectively. Conclusion Managing CF requires higher order executive function. Impairments may be sufficient to interfere with self-care and the ability to perform everyday tasks efficiently. At which point in the CF disease trajectory these difficulties begin, and what may attenuate them, has yet to be determined.

Artificial intelligence applications within the geosciences are becoming increasingly common, yet there are still many challenges involved in adapting established techniques to geoscience data sets. Applications in the realm of volcanic hazards assessment show great promise for addressing such challenges. Here, we describe a Jupyter Notebook we developed that ingests real-time Global Navigation Satellite System (GNSS) data streams from the EarthCube CHORDS (Cloud-Hosted Real-time Data Services for the geosciences) portal TZVOLCANO, applies unsupervised learning algorithms to perform automated data quality control (“noise reduction”), and explores autonomous detection of unusual volcanic activity using a neural network. The TZVOLCANO CHORDS portal streams real-time GNSS positioning data in 1[Formula: see text]s intervals from the TZVOLCANO network, which monitors the active volcano Ol Doinyo Lengai in Tanzania, through UNAVCO’s real-time GNSS data services. UNAVCO’s real-time data services provide near-real-time positions processed by the Trimble Pivot system. The positioning data (latitude, longitude and height) are imported into the Jupyter Notebook presented in this paper in user-defined time spans. The positioning data are then collected in sets by the Jupyter Notebook and processed to extract a useful calculated variable in preparation for the machine learning algorithms, of which we choose the vector magnitude for further processing. Unsupervised K-means and Gaussian Mixture machine learning algorithms are then utilized to locate and remove data points (“filter”) that are likely caused by noise and unrelated to volcanic signals. We find that both the K-means and Gaussian Mixture machine learning algorithms perform well at identifying regions of high noise within tested GNSS data sets. The filtered data are then used to train an artificial intelligence neural network that predicts volcanic deformation. Our Jupyter Notebook has promise to be used for detecting potentially hazardous volcanic activity in the form of rapid vertical or horizontal displacement of the Earth’s surface.

Pancreatic cancer has known precursor lesions with potential to develop into malignancy over time. At least 20% of pancreatic cancer evolves from mucinous cystic neoplasms and intraductal papillary mucinous neoplasms, which are often discovered incidentally.1,2 Current guidelines for the management of mucinous cystic neoplasms and intraductal papillary mucinous neoplasms include long-term surveillance, which is expensive and nontherapeutic, or surgical resection, which is associated with major risk and may not be an option for patients with significant concomitant illness.3.

Parenteral and enteral nutrition support are key components of care for various medical and physiological conditions in infants, children, and adults. Nutrition support practices have advanced over time, driven by the goals of safe and sufficient delivery of needed nutrients and improved patient outcomes. These advances have been, and continue to be, dependent on research and development studies. Such studies address aspects of enteral and parenteral nutrition support: formulations, delivery devices, health outcomes, cost-effectiveness, and related metabolism. The studies are supported by public funding from the government and by private funding from foundations and from the nutrition support industry. To build public trust in nutrition support research findings, it is important to underscore ethical research conduct and reporting of results for all studies, including those with industry sponsors. In 2019, American Society for Parenteral and Enteral Nutrition's (ASPEN's) Board of Directors established a task force to ensure integrity in nutrition support research that is done as collaborative partnerships between the public (government and individuals) and private groups (foundations, academia, and industry). In this ASPEN Position Paper, the Task Force presents principles of ethical research to guide administrators, researchers, and funders. The Task Force identifies ways to curtail bias and to minimize actual or perceived conflict of interests, as related to funding sources and research conduct. Notably, this paper includes a Position Statement to describe the Task Force's guidance on Public-Private Partnerships for research and funding. This paper has been approved by the ASPEN Board of Directors.

Background Quality improvement (QI) methods have been widely adopted in health care. Although theoretical frameworks and models for organizing successful QI programs have been described, few reports have provided practical examples to link existing QI theory to building a unit-based QI program. The purpose of this report is to describe the authors’ experience in building QI infrastructure in a large neonatal ICU (NICU). Methods A unit-based QI program was developed with the goal of fostering the growth of high-functioning QI teams. This program was based on six pillars: shared vision for QI, QI team capacity, QI team capability, actionable data for improvement, culture of improvement, and QI team integration with external collaboratives. Multiple interventions were developed, including a QI dashboard to align NICU metrics with unit and hospital quality goals, formal training for QI leaders, QI coaches imbedded in project teams, a day-long QI educational workshop to introduce QI methodology to unit staff, and a secure, Web-based QI data infrastructure. Results Over a five-year period, this QI infrastructure brought organization and support for individual QI project teams and improved patient outcomes in the unit. Two case studies are presented, describing teams that used support from the QI infrastructure. The Infection Prevention team reduced central line–associated bloodstream infections from 0.89 to 0.36 infections per 1,000 central line–days. The Nutrition team decreased the percentage of very low birth weight infants discharged with weights less than the 10th percentile from 51% to 40%. Conclusion The clinicians provide a pragmatic example of incorporating QI organizational and contextual theory into practice to support the development of high-functioning QI teams and build a unit-based QI program.

Aims: To update the benchmark from the 2006 National Survey, comparing users of NHS psychiatric intensive care (PICU) and low secure (LSU) services, and to define 'locked rehabilitation' (LRU) patient characteristics. Method: A cross-sectional census day questionnaire (November 2016) with a six month follow-up ending in May 2017.Results: 104 NHS units responded: 73 PICU, 644 patients; 17 LSU, 190 patients; 14 LRU, 183 patients. The typical PICU patient is younger, employed, stays for shorter periods, is more likely to suffer delayed discharge and mood disorder, have complex needs, have had mental health admissions in the last 12 months, be on 1:1 or higher observations, and have fewer antipsychotic and physical health medications but more benzodiazepines. The typical LSU patient is an out of area transfer, least likely to have been admitted for self-harm or non-concordance, and is of Black Other ethnic origin. The typical LRU patient is less likely to be married or have a long-term partner, has the lowest complex needs, but is most likely to have had physical examination and investigations.Discussion: There has been a rise in PICU and LSU patients from the Black and Minority Ethnic (BAME) population. Length of stay (LoS) for PICU and LSU patients has doubled; there are lower rates of delayed transfers of care.Conclusions : Our findings demonstrate that PICU and LSU services are providing care to the right patients as they were conceptualised in national guidance, and provide a benchmark for LRU patients.

Direct-acting antivirals (DAA) have replaced interferon (IFN)-based therapies for hepatitis C virus. In this retrospective clinical study, we examined differences in histopathologic features in paired liver biopsies collected from the same patient before and after DAA and correlated these findings with clinical outcome. Biopsies (n = 19) were evaluated by quantitative imaging analysis to measure steatosis and fibrosis. Most patients had decreased steatosis in their post-treatment, follow-up biopsies. However, one patient had a striking increase in steatosis (from 0.86 to 6.32%) and later developed decompensated cirrhosis and hepatocellular carcinoma (HCC). This patient had a marked increase in fibrosis between biopsies, with a CPA of 6.74 to 32.02. Another patient, who already had bridging fibrosis at the time of her pre-treatment biopsy, developed cholangiocarcinoma after DAA. Even though the overall inflammatory activity in the post-treatment biopsies significantly decreased after treatment, 60% of patients had persistent portal lymphocytic inflammation. In summary, DAAs decreased steatosis and hepatic inflammation in most patients, although some may have persistence of lymphocytic portal inflammation. Patients known to have advanced fibrosis at treatment initiation and who have other risk factors for ongoing liver injury, such as steatosis, should be followed closely for the development of adverse outcomes, such as portal hypertension and primary liver cancers.

Purpose The role of women in the United States military is expanding. Women are now authorized to serve in all military occupations, including special operations and frontline combat units, which places them at increased risk of combat exposure and injury. Little is known regarding the impact of these injuries on the health of military women. Methods We conducted a retrospective matched cohort study of women service members who were injured during combat operations in Iraq and Afghanistan. Injured women were individually matched to non-injured controls at a 1:4 ratio. Medical diagnostic codes were abstracted from outpatient encounters in electronic health records, and hierarchical clustering was conducted to identify clusters of diagnostic codes, termed “health profiles.” Conditional logistic regression was used to determine whether combat-related injury predicted membership in the profiles. Results The study sample included 590 injured women and 2360 non-injured controls. Cluster analysis identified six post-deployment health profiles: low morbidity, anxiety/headache, joint disorders, mixed musculoskeletal, pregnancy-related, and multimorbidity. Combat-related injury predicted membership in the anxiety/headache (odds ratio, 1.73; 95% confidence interval, 1.38–2.16) and multimorbidity (odds ratio, 3.43; 95% confidence interval, 2.65–4.43) profiles. Conclusions Combat-related injury is associated with adverse post-deployment health profiles among military women, and women with these profiles may experience increased health care burden. As future conflicts will likely see a greater number of women with combat exposure and injury, health outcomes research among military women is paramount for the purposes of medical planning and resource allocation.

Objective To determine the association of overnight extubation (OE) with extubation success. Study design Retrospective cohort study in three NICUs from 2016 to 2020. Infants without congenital anomalies, less than 1500 grams at birth, who were ventilated and received an extubation attempt were included. Primary exposure was OE (7:00 pm–6:59 am) and outcome was extubation success defined as no mechanical ventilation for at least 7 days after extubation. Results A total of 76/379 (20%) infants received OE. Infants extubated during the daytime were older and had higher illness severity markers. Extubation success rates did not differ for overnight (57/76, 75%) versus daytime extubations (231/303, 76%) after adjusting for confounders (adjusted relative risk 0.95, 95% CI 0.82–1.11). Conclusion Though infants in our cohort undergoing daytime and OE were dissimilar, extubation success rates did not differ. Larger multicenter studies are needed to test our findings and identify markers of extubation readiness in preterm infants.

Maternal systemic inflammation increases risk for neurodevelopmental disorders like autism, ADHD, and schizophrenia in offspring. Notably, these disorders are male-biased. Studies have implicated immune system dysfunction in the etiology of these disorders, and rodent models of maternal immune activation provide useful tools to examine mechanisms of sex-dependent effects on brain development, immunity, and behavior. Here, we employed an allergen-induced model of maternal inflammation in rats to characterize levels of mast cells and microglia in the perinatal period in male and female offspring, as well as social, emotional, and cognitive behaviors throughout the lifespan. Adult female rats were sensitized to ovalbumin (OVA), bred, and challenged intranasally on gestational day 15 of pregnancy with OVA or saline. Allergic inflammation upregulated microglia in the fetal brain, increased mast cell number in the hippocampus on the day of birth, and conferred region-, time- and sex- specific changes in microglia measures. Additionally, offspring of OVA-exposed mothers subsequently exhibited abnormal social behavior, hyperlocomotion, and reduced cognitive flexibility. These data demonstrate the long-term effects of maternal allergic challenge on offspring development and provide a basis for understanding neurodevelopmental disorders linked to maternal systemic inflammation in humans.

Bioacoustic methods play an increasingly important role for the detection of insects in a range of surveillance and monitoring programmes.Weak‐flying insects evade detection because they do not yield sufficient audio information to capture wingbeat and harmonic frequencies. These inaudible insects often pose a significant threat to food security as pests of key agricultural crops worldwide.Automatic detection of such insects is crucial to the future of crop protection by providing critical information to assess the risk to a crop and the need for preventative measures.We describe an experimental set‐up designed to derive audio recordings from a range of weak‐flying aphids and beetles using an LED array.A rigorous data processing pipeline was developed to extract meaningful features, linked to morphological characteristics, from the audio and harmonic series for six aphid and two beetle species.An ensemble of over 50 bioacoustic parameters was used to achieve species discrimination with a success rate of 80%. The inclusion of the dominant and fundamental frequencies improved prediction between beetles and aphids because of large differences in wingbeat frequencies.At the species level, error rates were minimized when harmonic features were supplemented by features indicative of differences in species' flight energies., Data processing pipeline for the automatic identifcation of weak‐flying insects. Insects fly through an opto‐acoustic sensor triggering an audio recording to be made of the sound of their flight. Data are then processed to enable feature extraction. These features are fed into classification algorithms, namely random forests, which are then checked for validity before being sent to the end user for interpretation.

Magnesium status and vitamin B6 intake have been linked to mental health and/or quality of life (QoL). In an 8-week Phase IV randomised controlled study in individuals with low magnesemia and severe/extremely severe stress but who were otherwise healthy, greater stress reduction was achieved with magnesium combined with vitamin B6 than with magnesium alone. We present a previously unreported secondary analysis of the effect of magnesium, with and without vitamin B6, on depression, anxiety, and QoL. Adults with Depression Anxiety Stress Scales (DASS-42) stress subscale score >18 were randomised 1:1 to magnesium + vitamin B6 combination (Magne B6® ; daily dose 300 and 30 mg, respectively) or magnesium alone (Magnespasmyl® ; daily dose 300 mg). Outcomes included changes from baseline in DASS-42 depression and anxiety scores, and QoL (Short Form-36 Health Survey). DASS-42 anxiety and depression scores significantly improved from baseline to week 8 with both treatments, particularly during the first 4 weeks. Improvement in QoL continued over 8 weeks. Participants' perceived capacity for physical activity in daily life showed greater improvement with magnesium + vitamin B6 than magnesium alone (Week 4). In conclusion, magnesium supplementation, with or without vitamin B6, could provide a meaningful clinical benefit in daily life for individuals with stress and low magnesemia.

IntroductionLaryngotracheal and pharyngo-oesophageal trauma present military providers with especially difficult, life-threatening challenges. Although effective treatment strategies are crucial, there is no clear consensus. This study of combat injuries from Iraq and Afghanistan describes initial treatment outcomes.MethodsUS service members who sustained ‘laryngotracheal’ and ‘pharyngoesophageal’ injuries while deployed in military operations from 2003 to 2017 were identified from the Expeditionary Medical Encounter Database. Those with inhalation or ingestion injuries and an Injury Severity Score (ISS) ResultsA total of 111 service members met inclusion criteria. Nearly one-third (32.4%) were killed in action (KIA) or died of wounds (DoW). Fatality was not significantly associated with age, theatre of operation, type of injury or mechanism of injury, but was associated with a higher ISS and those in the Marines. Although survival rates were not significantly different, the frequency of these injuries decreased after the introduction of cervical collar protection in 2007. Of those who DoW or survived, 41.1% required a surgical airway. Tracheobronchoscopy was performed in 25.6%, oesophagoscopy in 20.0% and oesophagram in 6.7%. Of the 85 with penetrating neck injuries, 43 (50.6%) underwent neck exploration, in which 31 (72.1%) required intervention.ConclusionsSevere laryngotracheal and pharyngo-oesophageal injuries have a high fatality rate and demand prompt treatment from skilled providers. Further work will elucidate preventive measures and clear management algorithms to optimise outcomes.

The COVID-19 pandemic has led to a rapid change in the way healthcare is provided. Pre-existing clinical models of care delivery have had to merge with a new way of working; driven by infection control and minimising the transmission of the virus. In an acute psychiatric setting, this has required many of the existing systems to be deconstructed and rebuilt in a way which at times is unrecognisable. For psychiatric intensive care unit (PICU) services, the clinical model is simultaneously suited and opposed to the approach adopted to contain and manage the COVID-19 pandemic. This article explores how systems and processes used on a PICU can be translated to tackle challenges imposed by the coronavirus disease.

OBJECTIVES This project was developed because residents need to gain knowledge and experience in promptly recognizing patients with suicidal ideation. Our study allowed pediatric interns the opportunity to manage a simulated 16-year-old actively suicidal patient in the resident continuity clinic for a well-child visit. METHODS During their first year, each resident receives simulation training. The simulation scenario for this study involves the use of a standardized patient (SP). Sessions take place in the pediatric simulation center and are recorded for observation and review. The scenario was scripted and piloted to ensure standardization in educational intervention. Postscenario, participants have a nonjudgmental debriefing with the attending physician and the SP. An anonymous survey is completed after training. Enrollment was June 2016-September 2019, with two to three 1-hour cases monthly. RESULTS Seventy-one postgraduate year-1 residents participated. Sixty-one residents left the suicidal patient alone/unobserved. Fifteen participants never learned of the intent of suicide during their initial intake with the patient but believed that she was depressed. The mean time to ask about suicidal ideation, when applicable, was 8:32 minutes (standard deviation 4:10 minutes, range 2:15-24:48 minutes). Common learning themes included realistic exposure to an actively suicidal patient and simulation debriefing/direct feedback from the SP. CONCLUSIONS Practicing this crucial but somewhat rare primary care mental health emergency for all interns was possible when structured monthly. Feedback was extremely positive, with learners' feeling more prepared postsimulation. Our simulation experience also allows supervisors to assess intern's individual abilities to communicate in a difficult patient scenario which is an important physician competency as defined by the Accreditation Council for Graduate Medical Education.

Purpose We tested the acute effect of breakfast (ready-to-eat-cereal [RTEC] and milk) versus (vs.) no breakfast on cognitive function and subjective state in adolescents. Methods Healthy adolescents (n = 234) aged 11–13 years were recruited to take part in this school-based, acute, randomised, controlled, parallel groups trial with two interventions; Breakfast or No Breakfast. The breakfast intervention consisted of ad libitum intake of RTEC (up to 70 g) with milk (up to 300 ml) administered in a naturalistic school breakfast programme environment. Cognitive function was assessed at baseline and + 70 and + 215 min post-intervention in a group-testing situation, similar to a school classroom context. The CANTAB test battery included: Simple Reaction Time (SRT), 5-Choice Reaction Time (5-CRT), Rapid Visual Information Processing (RVIP), and Paired Associates Learning (PAL; primary outcome). Data collection commenced January 2011 and ended May 2011. This trial was retrospectively registered at www.clinicaltrials.gov as NCT03979027 on 07/06/2019. Results A significant effect of the intervention (CMH[1] = 7.29, p z = 2.58, p p Conclusion Consuming breakfast has a positive acute effect on cognition in adolescents.

Wildfire is an annual threat for many rural communities in the Pacific Northwest region of the United States. In some severe events, evacuation is one potential course of action to gain safety from an advancing wildfire. Since most evacuations occur in a personal vehicle along the surrounding road network, the quality of this network is a critical component of a community's vulnerability to wildfire. In this paper, we leverage a high-resolution spatial dataset of wildfire burn probability and mean fireline intensity to conduct a regional-scale screening of wildfire evacuation vulnerability for 696 Oregon and Washington rural towns. We characterize each town’s surrounding road network to construct four simple road metrics related to the potential to quickly and safely evacuate: (1) the number of paved lanes leaving town that intersect a fixed-distance circular buffer; (2) the variety of lane directions available for egress; (3) the travel area that can be reached within a minimum distance while constrained only to movement along the paved road network; and (4) the sum of connected lanes at each intersection for the road network within a fixed-distance circular buffer. We then combine the road metrics with two metrics characterizing fire hazard of the surrounding landscape through which evacuation will occur: (1) burn probability and (2) mean fireline intensity. By combining the road and fire metrics, we create a composite score for ranking all towns by their overall evacuation vulnerability. The most vulnerable towns are those where poor road networks overlap with high fire hazard. Often, these towns are located in remote, forested, mountainous terrain, where topographic relief constrains the available road network and high fuel loads increase wildfire hazard. An interactive map of all road quality and fire hazard metrics is available at https://www.fs.fed.us/wwetac/brief/evacuation.php .

Venezuela is in the midst of a humanitarian crisis. In addition to food and medicinal shortages, violent crime has risen dramatically since 2014, spurring a mass exodus from the country. In order to cope with persistent material, informational, and digital infrastructural breakdowns that their friends and family in Venezuela are facing, members of the Venezuelan diaspora have turned to social media platforms to support people they left behind. Through semi-structured interviews and participant observation, I uncover the ways participants form a critical infrastructure for people in Venezuela. I describe participants' actions as infrastructural care --- infrastructural action as a form of caring for others at a distance through the ongoing management of resources, relationships, and infrastructures. Infrastructural care consists of relational, negotiated, and dialectic actions that provide critical support while also generating ongoing tensions as participants are geographically separated from the crisis and, through their involvement, are forced to confront their own experiences of trauma. In addition to proposing the lens of infrastructural care, this paper contributes to our understandings of the ways people cope with an ongoing humanitarian crisis at a distance and how social media platforms fit in with wider ecologies of efforts.

Introduction Many veterans qualify for health benefits but generally not dental care. This study examines differences in oral health status between veterans and nonveterans in the U.S. to determine how various factors, including socioeconomic, general health, and tobacco use, impact former service members’ oral health. Materials and Methods Data from 11,539 dentate adults participating in the National Health and Nutrition Examination Survey (2011-2014) were used. Outcome variables included decayed teeth (DT), missing teeth (MT), filled teeth (FT), caries experience (DMFT), and periodontitis (PD). Covariates included demographic and socioeconomic factors, deployment, smoking, depression, hypertension, hyperlipidemia, and diabetes. Logistic regression modelling was used to assess associations between these factors and oral health outcomes. Results Veterans represent about 9% of the U.S. population. There was a higher prevalence of PD, MT, FT, and DMFT among veterans than nonveterans. Veterans were more likely to have PD (OR, 1.8; 95% CI, 1.3 to 2.5) and higher DMFT (OR, 2.9; 95% CI, 2.4 to 3.4); however, after controlling for other covariates, military service was only associated with FT (OR, 1.3; 95% CI, 1.1 to 1.6) and higher DMFT (OR, 1.6; 95% CI, 1.2 to 1.9). Conclusions Because veterans are more likely to originate from groups at a higher risk for poor oral health (older adults, smokers, males, diabetics), the prevalence of adverse oral health conditions are higher among veterans compared to nonveterans. Overall, military service is not associated with PD or untreated dental caries but is associated with indicators suggesting veterans have had more dental treatment (FT and DMFT). There is substantial unmet oral health care need primarily related to periodontitis among veterans.

Older age is associated with deteriorating health, including escalating risk of diseases such as cancer, and a diminished ability to repair following injury. This rise in age-related diseases/co-morbidities is associated with changes to immune function, including in myeloid cells, and is related to immunosenescence. Immunosenescence reflects age-related changes associated with immune dysfunction and is accompanied by low-grade chronic inflammation or inflammageing. This is characterised by increased levels of circulating pro-inflammatory cytokines such as tumor necrosis factor (TNF), interleukin (IL)-1β and IL-6. However, in healthy ageing, there is a concomitant age-related escalation in anti-inflammatory cytokines such as transforming growth factor-β1 (TGF-β1) and IL-10, which may overcompensate to regulate the pro-inflammatory state. Key inflammatory cells, macrophages, play a role in cancer development and injury repair in young hosts, and we propose that their role in ageing in these scenarios may be more profound. Imbalanced pro- and anti-inflammatory factors during ageing may also have a significant influence on macrophage function and further impact the severity of age-related diseases in which macrophages are known to play a key role. In this brief review we summarise studies describing changes to inflammatory function of macrophages (from various tissues and across sexes) during healthy ageing. We also describe age-related diseases/co-morbidities where macrophages are known to play a key role, focussed on injury repair processes and cancer, plus comment briefly on strategies to correct for these age-related changes.

Topotecan is potent anti-cancer drug approved for various malignancies but hematopoietic toxicities undermine its wider application and use of its most effective dose. This study aims to improve these limitations through inhalation-delivery. The pharmacokinetics, efficacy, and toxicity of 2–5 times lower inhalation doses of topotecan dry-powder were compared with the standard intravenous (IV) delivery once/twice-a-week. Human-derived EGFR-mutant (H1975), KRAS-mutant (A549), and EGFR/KRAS wild-type (H358) orthotopic and distant lung tumors were evaluated in murine models. Inhalation of 1 mg/kg topotecan significantly improved the half-life and drug exposure (area under the curve, AUC) compared to 5 mg/kg via IV-delivery. AUCs (h*ng/mL) for inhaled/IV topotecan in plasma, lung, liver, and brain were, 831/888, 60,000/1080, 8380/4000, and 297/15, respectively; while the half-life was also greatly increased in these tissues. The average lung tumor burden of H358-derived tumors was reduced from 15.0 g to 8.4 g (44%) in rats treated once-a-week with 2 mg/kg IV and 1.8 g (88%) with 1 mg/kg inhaled topotecan, corroborating previous findings using A549- and H1975-derived orthotopic lung tumors. Importantly, inhaled topotecan showed superior efficacy in suppressing lung tumors at distant sites. The growth of H1975- and H358-derived subcutaneous xenografts were completely arrested and A549-derived tumors were significantly reduced in mice treated twice-a-week with 1 mg/kg inhaled topotecan compared to a minor (H1975 and H358) or no reduction (A549) with twice-a-week 5 mg/kg IV topotecan.

The built environment of an older person’s home can reduce or promote the possibility of a fall or other injury. A user-friendly tool can help the residents to evaluate their home environment withi...

Background Data visualization techniques were used to ascertain (i) site-specific effects of cigarette smoking on the periodontium compared to never-smokers; (ii) patterns of site-specific effects by age among current and never-smokers using contour maps. Methods Data from 10,713 dentate participants aged ≥30y in NHANES 2009-2014 were used. Pocket depth (PD) and clinical attachment level (CAL) for 6 sites/tooth were ascertained by smoking status and plotted using contour maps to identify new patterns. Results In the overall sample, 19%(n = 2,015) were current smokers and 56%(n = 6,013) were never-smokers. Contour maps of the overall sample showed teeth/sites most affected with mean PD>2.1mm were molars (2,3,15,18,19,30,31) in mesio-lingual (ML) and disto-lingual (DL) sites. Most affected sites for current smokers were interproximal sites of most posterior teeth. Among never-smokers, fewer teeth/sites were affected with PD>2.1mm, while among smokers, number of affected teeth/sites increased with age. Overall, teeth/sites most affected with mean CAL≥2.1mm were noted in 2,3(ML), 3(DL), 14(DF,DL), 15(MF,ML), 18(ML), 19(DL,ML), and 30-31(ML,DL) with upper anterior teeth least affected. Among current smokers, several teeth/sites were affected (CAL≥2.1mm): 2,3(all 6 sites), 4(ML,DL), 9(ML), 11-21(DL), 13-18(DF, ML, MIL, DL), 19-20(DF,ML,MIL), 14-18(MIF), 21(MIF, ML, DL), 22(MF), 23-27(MIL), 24-26(MIL, MF, DF in 26), 27(MF), 28(MF,ML,DL), 29-31(all 6 sites except MIF 30,31). As age increased, more teeth/sites were affected among smokers and by the 5th decade nearly all teeth/sites had CAL≥2.0mm. Conclusions Contour mapping identifies patterns and dramatically visualizes the substantial periodontal site-specific differences. Current smokers had more affected teeth and/or periodontal sites with a different contour pattern than never-smokers. This article is protected by copyright. All rights reserved.

The opening of a new station on an existing passenger rail route increases accessibility to rail services, resulting in improved travel conditions for current passengers and stimulating new “induced” demand. However, these changes are not realized immediately, resulting in what is commonly referred to as a demand “ramp-up” period. This paper explores the concept of demand ramp-up and the corresponding impacts on ridership and passenger characteristics in the context of the Milwaukee Airport Rail Station, which opened in January 2005 along an existing Amtrak route between Milwaukee and Chicago. Analysis of ridership data from the new station indicated that the ramp-up period was three years; however, the percentage of steady-state ridership at each year of the ramp-up period was lower than the corresponding figures from other studies. The expected impact of the new station on adjacent stations was generally realized for ridership and access patterns, with approximately half of the new ridership being diverted from other stations while the other half were induced trips. Ridership at the new station was comprised of more business travelers than originally anticipated. However, in general, the other predicted outcomes related to the extent of usage of the station have not been realized after 11 years of operation. The results of this paper are instructive to provide planners and sponsors of passenger rail projects with a better understanding of the extent of demand ramp-up for new stations and how the characteristics of passengers evolve during the ramp-up period.

OBJECTIVE Children with medical complexity (CMC) have significant health care costs, but they also experience substantial unmet health care needs, hospitalizations, and medical errors. Their parents often report psychosocial stressors and poor care satisfaction. Complex care programs can improve the care for CMC. At our tertiary care institution, we developed a consultative complex care program to improve the quality and cost of care for CMC and to improve the experience of care for patients and families. METHODS To address the needs of CMC at our institution, we developed the Compass Care Program, a consultative complex care program across inpatient and outpatient settings. Utilization data [hospital admissions per patient month; length of stay per admission; hospital days per patient month; emergency department (ED) visits per patient month; and institutional charges per patient month] and caregiver satisfaction data (obtained via paper survey at outpatient visits) were tracked over the period of participation in the program and compared preenrollment and postenrollment for program participants. RESULTS Participants had significant decreases in hospital admissions per patient month, length of stay per admission, hospital days per patient month, and charges per patient month following enrollment (P

Background Two devastating sequential hurricanes impacted Puerto Rico during September of 2017. The hurricanes were traumatic and created social and ecological upheaval throughout Puerto Rico, and subsequently in communities of Central Florida where affected Puerto Ricans migrated. The 2017 hurricane season exposed and exacerbated previous long-standing socio-political, economic, environmental, and health crises, generating a humanitarian emergency in the country. The consequences of these human-ecological disasters destroyed much of Puerto Rico’s residential and environmental infrastructure, displacing thousands of people and resulting in an unprecedented migration to the United States. We report on the lived experience of the investigator team and partnership in conducting community-based formative research subsequent to this disaster, research that aimed to identify salient issues relating to the impact of Hurricanes Irma and María on Puerto Rican communities both in Puerto Rico and in Central Florida. Discussion The challenges faced during the conduct of this research include but are not limited to (1) emotional distress of participants and team members, (2) access to affected populations, and (3) precarious environmental factors, such as unstable infrastructure. To address these challenges, the researchers applied a Critical Medical Ecological paradigm along with qualitative methods to assist constructing explanatory models while obtaining internally-valid (from the community perspective), cathartic narrative accounts of the lived experience of hurricane survivors. The experience of the research team may help inform other investigators conducting applied research during a humanitarian crisis. Conclusion Lessons learned in this research included: (1) usefulness of applying the Critical Medical Ecological model in the development of the project, (2) incorporating participation and methods that prioritize authenticity, (3) understanding the trauma experience and using study methods sensitive to it, and (4) innovating with best approaches to conduct the study given the challenges in post-hurricane Puerto Rico. These lessons could provide new insights on how to conduct in-depth participatory health research with community members who have been traumatized and – often – displaced. This research also demonstrates the value of pre-existing partnerships, critical consciousness in the field team, and medical ecological modeling as experiential for organizing complex, inter-related, multi-level variables that explain community and individual impact of environmental disasters.

Three‐dimensional lung organoids (LOs) derived from pluripotent stem cells have the potential to enhance our understanding of disease mechanisms and to enable novel therapeutic approaches in neonates with pulmonary disorders. We established a reproducible ex vivo model of lung development using transgene‐free human induced pluripotent stem cells generated from fetuses and infants with Bochdalek congenital diaphragmatic hernia (CDH), a polygenic disorder associated with fetal lung compression and pulmonary hypoplasia at birth. Molecular and cellular comparisons of CDH LOs revealed impaired generation of NKX2.1+ progenitors, type II alveolar epithelial cells, and PDGFRα+ myofibroblasts. We then subjected these LOs to disease relevant mechanical cues through ex vivo compression and observed significant changes in genes associated with pulmonary progenitors, alveolar epithelial cells, and mesenchymal fibroblasts. Collectively, these data suggest both primary cell‐intrinsic and secondary mechanical causes of CDH lung hypoplasia and support the use of this stem cell‐based approach for disease modeling in CDH., We established a reproducible ex vivo model of lung development using transgene‐free human induced pluripotent stem cells generated from fetuses and infants with Bochdalek congenital diaphragmatic hernia (CDH). Both primary cell‐intrinsic and secondary causes of CDH lung hypoplasia were identified, and mechanical compression was associated with alterations in lung organoid epithelial and mesenchymal gene regulation.

Objective: To characterize serious inhalation injuries seen during recent military operations, and assess whether bronchoscopic severity findings were associated with clinical presentation and outcomes. Methods: Service members who suffered inhalation injuries while deployed to Iraq, Afghanistan, or Syria from 2001-2018 were identified using ICD-9 and 10 codes from the Expeditionary Medical Encounter Database (EMED), which is abstracted from patient records in forward-deployed medical facilities. Further information including demographics, mechanism of injury, mortality, total burn surface area (TBSA), degree of facial burn, total Injury Severity Score (ISS), and first post-injury bronchoscopy notes were collected. Patients were excluded with ISS less than 16 or without sufficient details regarding bronchoscopy. Injuries were grouped based on bronchoscopic Abbreviated Injury Scores (AIS) into low-grade (AIS of 1), moderate-grade (AIS of 2), or high-grade (AIS of 3 or 4). Results: 91 patients met inclusion criteria, with no significant differences in age, gender, paygrade, or service branch between degrees of injury. There were no statistical correlations between grade of injury and battle versus non-battle injury, blast versus non-blast mechanism, TBSA, or degree of facial burn. High-grade injuries had significantly higher ISS than low or moderate-grade injuries. After adjusting for ISS, the odds ratio of death was 10.4 (95% CI 1.47 to 74.53) for those with high-grade and 3.7 (95% CI 0.45 to 32.30) for those with moderate-grade compared to low-grade injuries. Conclusion: In this cohort of deployed military members with inhalation injuries, initial bronchoscopic severity findings are strongly associated with mortality even after adjusting for ISS. The AIS may be an important prognostic tool in all of those with serious inhalation injuries.

This paper studies equilibrium voluntary disclosures for a company financed with both debt and equity, where the firm's manager is compensated based on a linear combination of the market prices of the firm's equity and enterprise values (i.e., the sum of its values of equity and debt). Such compensation policies span “all equity” contracts, “all debt” contracts, and “all enterprise value” contracts. We show: (1) under both “all equity” and “all debt” contracts, increased debt always leads to reduced voluntary disclosure; (2) under “all enterprise value” contracts, increased debt has no effect on voluntary disclosure; (3) for all contracts that place positive weight on both equity and enterprise values, more debt leads to less (respectively, more) disclosure if the initial debt level is low (respectively, high); (4) increasing the weight on equity prices always induces less disclosure, so: (5) “all equity” contracts minimize disclosures, and “all debt” contracts maximize disclosures.

Long-term exposure to contaminated water can cause health effects, such as cancer. Accurate spatial prediction of inorganic compounds (e.g. arsenic) and pathogens in groundwater is critical for wat...

Healthcare providers may be ill-equipped to address the specific care needs of refugee/immigrant (RI) patient populations. We assessed continuing education (CE) training interests among HIV/AIDS, STD, and Hepatitis C (HASH) providers in New York State (NYS), United States, who serve RI patients from Latin America and the Caribbean (LAC). An online survey was completed by 156 HASH providers during a three-month period in Spring 2018. HASH providers serving LAC patients indicate interest in additional training to address the unique needs of the RI community. We noted a strong interest for more tailored learning opportunities in issues that impact refugee health. Copyright © 2020 Marriott et al. Published by Global Health and Education Projects, Inc. This is an open-access article distributed under the terms of the Creative Commons Attribution License CC BY 4.0.

Background Recent civilian and military data from the United States and the United Kingdom suggest that further reductions in mortality will require prehospital or preoperating room hemorrhage control and blood product resuscitation. The aims of this study were to examine the potential preventability of prehospital and early in-hospital fatalities, and to consider the geographical location of such incidents, to contextualize how the use of advanced resuscitative techniques could be operationalized. Methods Retrospective analysis of prehospital and early in-hospital trauma deaths from January to December 2017. Data were obtained from the Coroner/ME's Office. Each death was reviewed by a panel of two trauma surgeons and a forensic pathologist. Anatomical and physiological survivabilities were evaluated separately, and then combined, leading to a holistic assessment of preventability. Incident locations were mapped and analyzed using ArcGIS. Results Three hundred sixteen trauma deaths were identified. Two hundred thirty-one (73%) were deemed anatomically not survivable; 29 (9%) anatomically survivable, but only with hospital care; 43 (14%) anatomically survivable with advanced prehospital care; and 13 (4%) anatomically survivable with basic prehospital care. Physiologically, 114 (36%) of the patients had been dead for some time when found; 137 (43%) had no cardiorespiratory effort on arrival of Emergency Medical Services (EMS) at the scene; 24 (8%) had cardiorespiratory effort at the scene, but not on arrival at the emergency department; and 41 (13%) had cardiorespiratory effort on arrival at the emergency department, but died shortly after. Combining the assessments, 10 (3%) deaths were deemed probably not preventable, 38 (12%) possibly preventable, and the remaining 278 (85%) not preventable. Conclusion Twelve percent of trauma deaths were potentially preventable and might be amenable to advanced resuscitative interventions. Operationalizing this type of care will be challenging and will require either prehospital doctors, or very highly trained paramedics, nurses, or physician assistants. Level of evidence Epidemiological, level III.

Objectives To assess clinically asymptomatic infants with single-ventricle physiology (SVP) for sleep-disordered breathing (SDB) in the supine and car seat positions using polysomnography. Polysomnography results also were compared with results of a standard Car Seat Challenge to measure the dependability of the standard Car Seat Challenge. Study design This was an observational study of 15 infants with SVP. Polysomnography data included Obstructive Index, Central Index, Arousal Index, Apnea Hypopnea Index, and sleep efficiency. Polysomnography heart rate and oxygen saturation data were used to compare polysomnography with the standard Car Seat Challenge. Results Polysomnography demonstrated that all 15 infants had SDB and 14 had obstructive sleep apnea (Obstructive Index ≥1/hour) in both the supine and car seat positions. Infants with SVP had a statistically significant greater median Obstructive Index in the car seat compared with supine position (6.3 vs 4.2; P = .03), and median spontaneous Arousal Index was greater in the supine position compared with the car seat (20.4 vs 15.2; P = .01). Comparison of polysomnography to standard Car Seat Challenge results demonstrated 5 of 15 (33%) of infants with SVP with abnormal Obstructive Index by polysomnography would have passed a standard Car Seat Challenge. Conclusions Infants with SVP without clinical symptoms of SDB may be at high risk for SDB that appears worse in the car seat position. The standard Car Seat Challenge is not dependable in the identification of infants with SVP and SDB. Further studies are warranted to further delineate its potential impact of SDB on the clinical outcomes of infants with SVP.

In the dental industry, it seem no one has entertained the thought that if a dislocated mandible, in a Class II Skeletal relation could occlude or block the blood flow in in the STA.* Therefore stopping or impeding blood flow to the vertex of the head and therefor causing balding. Taking into consideration that in a healthy Class I Skeletal relation the clearance between the base of the skull and the eminence of the condyle is only 3.5mm.Pic 1 Orthodontic experience tells us that mandibles 3.5mm retrognathic and more are very common. The intent of this paper is to expose the facts and evidence that show the Class II Skeletal mandible is the cause of balding by blocking blood flow through the S.T.A. Balding of vertex can be avoided. A large array of research has been, and continues to be conducted to determine the causative agent for hair loss. Traditionally such investigation has focused on a number of varying topics, including but not limited to chromosome composition, genotype, and subsequent phenotype expression. However, little or no investigation has been conducted to deduce what effect the skeletal relationship has upon the initial development of hair loss. Through a series of observational case studies, it is evident that there is a relationship between malocclusion and hair loss. Specifically, through analysis of dental records, cephalometric radiographs, and visual observation of patients, there appears to be a correlation between Class II Skeletal malocclusion and subsequent hair loss. Further investigation yields that vascular anatomical differences between different skeletal schemes is associated with the development of hair loss. Keywords: Craniofacial Anomalies, Pediatric Dentistry, Orthodontics, Hair Loss, Baldness

IntroductionTraumatic brain injury (TBI) is the most common cause of death on the modern battlefield. In recent conflicts in Iraq and Afghanistan, the US typically deployed neurosurgeons to medical treatment facilities (MTFs), while the UK did not. Our aim was to compare the incidence, TBI and treatment in US and UK-led military MTF to ascertain if differences in deployed trauma systems affected outcomes.MethodsThe US and UK Combat Trauma Registries were scrutinised for patients with HI at deployed MTFs between March 2003 and October 2011. Registry datasets were adapted to stratify TBI using the Mayo Classification System for Traumatic Brain Injury Severity. An adjusted multiple logistic regression model was performed using fatality as the binomial dependent variable and treatment in a US-MTF or UK-MTF, surgical decompression, US military casualty and surgery performed by a neurosurgeon as independent variables.Results15 031 patients arrived alive at military MTF after TBI. Presence of a neurosurgeon was associated with increased odds of survival in casualties with moderate or severe TBI (p4, 95% CI 1.61×104 to 110.6×104, pConclusionsPresence of neurosurgeons increased the likelihood of survival after TBI. We therefore recommend that the UK should deploy neurosurgeons to forward military MTF whenever possible in line with their US counterparts.

Vagus nerve stimulator (VNS)-associated sleep disordered breathing (SDB) is a poorly understood side effect of VNS treatment. We present a patient with VNS-associated SDB who underwent sleep laboratory VNS titration, evaluation by drug-induced sleep endoscopy, and treatment including adenotonsillectomy and positive airway pressure therapy. This case is unique as it is the first to document, in real time, the inverse correlation of VNS current with airflow. This case offers unique insights into mechanisms and treatment of VNS-associated SDB, and a novel approach in its management. Most importantly, this case highlights the need for collaboration between physicians managing epilepsy with VNS and those managing sleep.

Abstract Screening and linkage to care are core, foundational strategies for HIV transmission prevention and for identifying People Living with HIV (PLHIV). In Romania – with an atypical experience in the HIV/AIDS epidemic – providing care for HIV+ patients identified early is a priority, though screening and testing can pose a challenge in some areas. Methods A survey of 125 clinical providers to explore important dimensions of HIV/ AIDS clinical care was conducted in Transylvania and Moldavia, where clinicians identified poor/ latent screening as a major problem in providing timely care and in preventing the spread of disease. We analyzed determinants of offering HIV screening/testing to patients using Pearson Chi-square analysis and logistic regression. Logistic regression generated Odds Ratios (OR) to reflect the magnitude of association between the relevant variables, with 95% confidence interval (95% CI) indicating statistical range. Results In total, 40.8% of providers did not provide HIV screening/testing to at least one segment of the population. Hospital-based providers were significantly more likely to offer HIV screening/testing to all segments than were non-hospital-based providers (58.1% v. 35.5%, respectively; p Discussion Reaching Romanian and global goals for reducing HIV require more timely screening and action based on positive status. Romanian clinicians are interested in expanding HIV screening/testing and are interested in participating in training that helps them feel more prepared to undertake this work.

The proverbial benefits of prevention over cure are self-evident—and yet we are reluctant to invest in staying healthy. Resolution of this age-old dilemma begins with a timeless truth: the benefits of good health come at a cost: prevention is not better than cure at any price. That logic leads to a testable—and refutable—proposition: that prevention should be favoured when an imminent, high-risk, high-impact hazard can be averted at relatively low cost. Application of this idea helps to explain why cigarette smoking is still commonplace, why the world was not ready for the COVID-19 pandemic, why the idea of a ‘sin tax’ is misconceived, why billions still do not have access to safe sanitation, why the response to climate change has been so slow, and why public health advice often falls on deaf ears. Much more money and effort are invested in health promotion and prevention today than is commonly thought, but the enormous avoidable burden of illness is reason to seek incentives for investing still more. The principles, together with a series of case studies in diverse settings, offer 12 lessons for prevention. These are methods and motives for shifting the balance away from reactive medical treatment, bypassing illness and injury, to promote better health and well-being.

The SARS-CoV-2 Gamma variant spread rapidly across Brazil, causing substantial infection and death waves. We use individual-level patient records following hospitalisation with suspected or confirmed COVID-19 to document the extensive shocks in hospital fatality rates that followed Gamma’s spread across 14 state capitals, and in which more than half of hospitalised patients died over sustained time periods. We show that extensive fluctuations in COVID-19 in-hospital fatality rates also existed prior to Gamma’s detection, and were largely transient after Gamma’s detection, subsiding with hospital demand. Using a Bayesian fatality rate model, we find that the geographic and temporal fluctuations in Brazil’s COVID-19 in-hospital fatality rates are primarily associated with geographic inequities and shortages in healthcare capacity. We project that approximately half of Brazil’s COVID-19 deaths in hospitals could have been avoided without pre-pandemic geographic inequities and without pandemic healthcare pressure. Our results suggest that investments in healthcare resources, healthcare optimization, and pandemic preparedness are critical to minimize population wide mortality and morbidity caused by highly transmissible and deadly pathogens such as SARS-CoV-2, especially in low- and middle-income countries., One sentence summary COVID-19 in-hospital fatality rates fluctuate dramatically in Brazil, and these fluctuations are primarily associated with geographic inequities and shortages in healthcare capacity.

This study was conducted to investigate the adherence of Daily Food Guides (DFGs) among older Taiwanese, and the relationship of dietary quality and frailty. 154 functional independent older adults who were retirement home residents or community dwellers involved in congregate meal services were recruited. DFGs adherence was measured using a novel Taiwanese Healthy Index (T-HEI). Dietary quality was further assessed using Dietary Approach to Stop Hypertension (DASH) and Mediterranean Diet Score (MDS). Frailty was defined using modified Fried’s criteria. Of the total participants, 12.3% were considered non-frail individuals, while 77.3% were prefrail, and 10.4% were frail. Compared to non-frail participants, prefrail and frail individuals indicated significantly lower adherence to DFGs (ptrend = 0.025). Intake of dark or orange vegetables (ptrend = 0.010), whole grains (ptrend = 0.007), as well as nuts and seeds (ptrend = 0.029) by non-frail individuals were significantly higher than the levels by prefrail and frail individuals. Linear regression model adjusted for age, gender, and functional ability showed that T-HEI was inversely associated with frailty status (β = −0.16 ± 0, p = 0.047), but additional adjustment for nutritional status attenuated the association (β = −0.14 ± 0, p = 0.103). A similar relationship was observed for DASH but not MDS (DASH: β = −0.18 ± 0.01, p = 0.024; MDS: β = −0.06 ± 0.02, p = 0.465). After adjustment for confounders, the association was not observed. However, the distribution of whole grains component in both DASH and MDS was significantly higher in non-frail than prefrail and frail individuals, indicating the importance of whole grains intake in frailty prevention. In conclusion, higher adherence to DFGs and better dietary quality were associated with a lower prevalence of frailty. Higher nutrient-dense foods intake such as whole grains, dark or orange vegetables, nuts, and seeds mark a watershed in frailty prevention.