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Background: Establishing irremediability of suffering is a central challenge in determining the appropriateness of medical assistance in dying (MAiD) for patients with a psychiatric disorder. We sought to evaluate how experienced psychiatrists define irremediable psychiatric suffering in the context of MAiD and what challenges they face while establishing irremediable psychiatric suffering. Methods: We conducted a qualitative study of psychiatrists in the Netherlands with experience assessing irremediable psychiatric suffering in the context of MAiD. We collected data from in-depth, semistructured interviews focused on the definition of irremediable psychiatric suffering and on the challenges in establishing irremediability. We analyzed themes using a modified grounded theory approach. Results: The study included 11 psychiatrists. Although irremediable psychiatric suffering is a prospective concept, most participants relied on retrospective dimensions to define it, such as a history of failed treatments, and expressed that uncertainty was inevitable in this process. When establishing irremediable psychiatric suffering, participants identified challenges related to diagnosis and treatment. The main diagnostic challenge identified was the frequent co-occurrence of more than 1 psychiatric diagnosis. Important challenges related to treatment included assessing the quality of past treatments, establishing when limits of treatment had been reached and managing 'treatment fatigue.' Interpretation: Challenges regarding the definition, diagnosis and treatment of irremediable psychiatric suffering complicate the process of establishing it in the context of MAiD. Development of consensus clinical criteria for irremediable psychiatric suffering in this context and further research to understand 'treatment fatigue' among patients with psychiatric disorders may help address these challenges. Registration: This study was preregistered under osf.io/2jrnd., Medical assistance in dying (MAiD), also known as physician-assisted death, has been legalized in an increasing number of jurisdictions around the world. (1) In 2023, Canada will join a small [...]

Prognostic information is needed to balance benefits and risks of cancer treatment in older patients. Metabolomics-based scores were previously developed to predict 5- and 10-year mortality (MetaboHealth) and biological age (MetaboAge). This study aims to investigate the association of MetaboHealth and MetaboAge with 1-year mortality in older patients with solid tumors, and to study their predictive value for mortality in addition to established clinical predictors. This prospective cohort study included patients aged ≥ 70 years with a solid malignant tumor, who underwent blood sampling and a geriatric assessment before treatment initiation. The outcome was all-cause 1-year mortality. Of the 192 patients, the median age was 77 years. With each SD increase of MetaboHealth, patients had a 2.32 times increased risk of mortality (HR 2.32, 95% CI 1.59–3.39). With each year increase in MetaboAge, there was a 4% increased risk of mortality (HR 1.04, 1.01–1.07). MetaboHealth and MetaboAge showed an AUC of 0.66 (0.56–0.75) and 0.60 (0.51–0.68) for mortality prediction accuracy, respectively. The AUC of a predictive model containing age, primary tumor site, distant metastasis, comorbidity, and malnutrition was 0.76 (0.68–0.83). Addition of MetaboHealth increased AUC to 0.80 (0.74–0.87) (p= 0.09) and AUC did not change with MetaboAge (0.76 (0.69–0.83) (p= 0.89)). Higher MetaboHealth and MetaboAge scores were associated with 1-year mortality. The addition of MetaboHealth to established clinical predictors only marginally improved mortality prediction in this cohort with various types of tumors. MetaboHealth may potentially improve identification of older patients vulnerable for adverse events, but numbers were too small for definitive conclusions. The TENT study is retrospectively registered at the Netherlands Trial Register (NTR), trial number NL8107. Date of registration: 22–10-2019.

Temperature control trials in cardiac arrest patients have not reliably conferred neuroprotective benefit but have been limited by inconsistent treatment parameters. To evaluate the presence of a time dependent treatment effect, we assessed the association between preinduction time and clinical outcomes.

The article explores the relationality among colors in art and life. Topics discussed include quality of colors in a painting, value or intensity of color, effect of the scale or amount of a color within the painting on the outcome, interaction between colors driven by the artist's objectives and inner vision, and personal interactions with humans according to personal qualities, intensity of relationship, scale or amount of participation in the relationship, and awareness of the interaction.

Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene result in cystic fibrosis, a multiorgan disease characterized by aberrant epithelial cell fluid secretion. Recent studies describe a connection between CFTR malfunctioning and a heightened susceptibility to colorectal cancer (CRC). Here, we outline these links and suggest directions for further studies.

SHE CAME. SHE SAW. SHE RAN INTO SOME SHRUBS. WHEN ONE WRITER FOLLOWED HER FORMER MENTEE INTO THE FREERIDE WORLD QUALIFIER IN TAOS, N.M., A LOT OF THINGS HAPPEN. NAMELY, [...]

Think you know all about 3D flash memory and what the future has in store for this technology? Keep reading ... Thirty-five years ago, KIOXIA invented flash memory. Did you [...]

Joy, to the World Kai Shappley and Lisa Bunker. Clarion, $19.99 (240p) ISBN 978-0-06-324275-3 Young transgender activist Shappley's hopeful debut, written in collaboration with Bunker (Zenobia July), offers a downto-earth [...]

Arapahoe Basin is Colorado's renegade, a sack-lunch dog-party kind of place. Over the past decade it has nearly tripled in size--first into Montezuma Bowl, and now into The Beavers, forcing [...]

Background: Obesity may affect an individual’s immune response and subsequent risk of infection, such as a SARS-CoV-2 infection. It is less clear whether overweight and long-term obesity also constitute risk factors. We investigated the association between the degree and duration of overweight and obesity and SARS-CoV-2 infection. Methods: We analyzed data from nine prospective population-based cohorts of the Netherlands Cohorts Consortium, with a total of 99,570 participants, following a standardized procedure. Body mass index (BMI) and waist circumference (WC) were assessed two times before the pandemic, with approximately 5 years between measurements. SARS-CoV-2 infection was defined by self-report as a positive PCR or rapid-antigen test or as COVID-19 ascertained by a physician between March 2020 and January 2023. For three cohorts, information on SARS-CoV-2 infection by serology was available. Results were pooled using random-effects meta-analyses and adjusted for age, sex, educational level, and number of SARS-CoV-2 infection measurements. Results: Individuals with overweight (25 ≤ BMI < 30 kg/m2) (odds ratio (OR) = 1.08, 95%-confidence interval (CI) 1.04-1.13) or obesity (BMI ≥ 30 kg/m2) (OR = 1.43, 95%-CI 1.18–1.75) were more likely to report SARS-CoV-2 infection than individuals with a healthy body weight. We observed comparable ORs for abdominal overweight (men: 94 cm≤WC < 102 cm, women: 80 cm≤WC < 88 cm) (OR = 1.09, 95%-CI 1.04–1.14, I2= 0%) and abdominal obesity (men: WC ≥ 102 cm, women: WC ≥ 88 cm) (OR = 1.24, 95%-CI 0.999–1.55, I2= 57%). Individuals with obesity long before the pandemic, but with a healthy body weight or overweight just before the pandemic, were not at increased risk. Conclusion: Overweight and obesity were associated with increased risk of SARS-CoV-2 infection with stronger associations for obesity. Individuals with a healthier weight prior to the pandemic but previous obesity did not have an increased risk of SARS-CoV-2, suggesting that weight loss in those with obesity reduces infection risk. These results underline the importance of obesity prevention and weight management for public health.

Future fault-tolerant quantum computers will require storing and processing quantum data in logical qubits. Here we realize a suite of logical operations on a distance-2 surface code qubit built from seven physical qubits and stabilized using repeated error-detection cycles. Logical operations include initialization into arbitrary states, measurement in the cardinal bases of the Bloch sphere and a universal set of single-qubit gates. For each type of operation, we observe higher performance for fault-tolerant variants over non-fault-tolerant variants, and quantify the difference. In particular, we demonstrate process tomography of logical gates, using the notion of a logical Pauli transfer matrix. This integration of high-fidelity logical operations with a scalable scheme for repeated stabilization is a milestone on the road to quantum error correction with higher-distance superconducting surface codes.

Attention-deficit/hyperactivity disorder (ADHD) has been shown to continue into old age. Studies in children and younger adults show a reduction in hyperactive-impulsive symptoms, whereas the number of inattentive symptoms stays stable. The current study examined the lifetime stability of ADHD symptoms up to old age. Data on ADHD diagnosis and symptoms were collected in a two-phase side-study (N= 231) of the Longitudinal Aging Study Amsterdam. Paired ttests and ANCOVAs were used to analyze the data. Paired ttest suggests continuity of the number of reported ADHD symptoms currently present and present in childhood. The change in the balance of inattentive/hyperactive-impulsive symptoms at present and in childhood is also the same in persons with ADHD. Finally, the difference in the change in the balance of inattentive/hyperactive-impulsive symptoms in those with and without ADHD suggests continuity throughout the life span. Our results suggest that diagnostic criteria developed for younger adults may be used among older adults. However, we collected our data retrospectively, which may have biased our results. Future research should follow larger cohorts of patients with ADHD prospectively over the life span.

Genome-wide association analyses using high-throughput metabolomics platforms have led to novel insights into the biology of human metabolism1–7. This detailed knowledge of the genetic determinants of systemic metabolism has been pivotal for uncovering how genetic pathways influence biological mechanisms and complex diseases8–11. Here we present a genome-wide association study for 233 circulating metabolic traits quantified by nuclear magnetic resonance spectroscopy in up to 136,016 participants from 33 cohorts. We identify more than 400 independent loci and assign probable causal genes at two-thirds of these using manual curation of plausible biological candidates. We highlight the importance of sample and participant characteristics that can have significant effects on genetic associations. We use detailed metabolic profiling of lipoprotein- and lipid-associated variants to better characterize how known lipid loci and novel loci affect lipoprotein metabolism at a granular level. We demonstrate the translational utility of comprehensively phenotyped molecular data, characterizing the metabolic associations of intrahepatic cholestasis of pregnancy. Finally, we observe substantial genetic pleiotropy for multiple metabolic pathways and illustrate the importance of careful instrument selection in Mendelian randomization analysis, revealing a putative causal relationship between acetone and hypertension. Our publicly available results provide a foundational resource for the community to examine the role of metabolism across diverse diseases.

The Royal Dutch Society for Physical Therapy (KNGF) issued a clinical practice guideline for physical therapists that addresses the assessment and treatment of patients with nonspecific neck pain, including cervical [...]

This digest provides a demographic profile of family caregivers and discusses the emotional and physical burdens on family caregivers. It examines how caregivers cope with these burdens and highlights research findings on the most effective coping strategies. The digest concludes by summarizing the challenges to the helping profession in addressing the needs of family caregivers. (TE)

•What is the primary question addressed by this study?This study examined whether the Cortisol Awakening Response (CAR) could be a biomarker for cognitive change during electroconvulsive therapy (ECT).•What is the main finding of this study?We found no significant associations between the CAR and cognitive change during the ECT course in (un)adjusted models.•What is the meaning of the finding?Our results indicate that the CAR is not usable as a biomarker for ECT-induced cognitive change during the ECT course.

Coronary artery calcification (CAC), a measure of subclinical atherosclerosis, predicts future symptomatic coronary artery disease (CAD). Identifying genetic risk factors for CAC may point to new therapeutic avenues for prevention. Currently, there are only four known risk loci for CAC identified from genome-wide association studies (GWAS) in the general population. Here we conducted the largest multi-ancestry GWAS meta-analysis of CAC to date, which comprised 26,909 individuals of European ancestry and 8,867 individuals of African ancestry. We identified 11 independent risk loci, of which eight were new for CAC and five had not been reported for CAD. These new CAC loci are related to bone mineralization, phosphate catabolism and hormone metabolic pathways. Several new loci harbor candidate causal genes supported by multiple lines of functional evidence and are regulators of smooth muscle cell-mediated calcification ex vivo and in vitro. Together, these findings help refine the genetic architecture of CAC and extend our understanding of the biological and potential druggable pathways underlying CAC.

IN THE LATE 90S, VAIL'S EXPANSION INTO OUTER MONGOLIA CREATED SOME OF THE MOST DANGEROUS LIFT ACCESSED TERRAIN IN SKIDOM. A ZONE KNOWN AS EAST VAIL. IT REMAINED A SECRET [...]

There's more to being a great skier than being on great gear. But truth be told, you gotta start with your gear. Especially if you haven't been on the new [...]

How do you mourn the toss of the person who made you who you are? By using what he gave you: Skiing. When I was growing up in the '80s, [...]

AbstractThis article is a clinical guide which discusses the “state-of-the-art” usage of the classic monoamine oxidase inhibitor (MAOI) antidepressants (phenelzine, tranylcypromine, and isocarboxazid) in modern psychiatric practice. The guide is for all clinicians, including those who may not be experienced MAOI prescribers. It discusses indications, drug-drug interactions, side-effect management, and the safety of various augmentation strategies. There is a clear and broad consensus (more than 70 international expert endorsers), based on 6 decades of experience, for the recommendations herein exposited. They are based on empirical evidence and expert opinion—this guide is presented as a new specialist-consensus standard. The guide provides practical clinical advice, and is the basis for the rational use of these drugs, particularly because it improves and updates knowledge, and corrects the various misconceptions that have hitherto been prominent in the literature, partly due to insufficient knowledge of pharmacology. The guide suggests that MAOIs should always be considered in cases of treatment-resistant depression (including those melancholic in nature), and prior to electroconvulsive therapy—while taking into account of patient preference. In selected cases, they may be considered earlier in the treatment algorithm than has previously been customary, and should not be regarded as drugs of last resort; they may prove decisively effective when many other treatments have failed. The guide clarifies key points on the concomitant use of incorrectly proscribed drugs such as methylphenidate and some tricyclic antidepressants. It also illustrates the straightforward “bridging” methods that may be used to transition simply and safely from other antidepressants to MAOIs.

Research on parenting with particular attention to parental influence on such matters as self-esteem, academic achievement, social support, and parent-child communication is synthesized in this document. Parental concerns are noted and discussed from an historical vantage point and compared with what concerns parents most today. Sources of help for those concerns are presented as well. The monograph provides an annotated bibliography for parents of school-aged children and adolescents. Resources included in the bibliography range from those focusing on the general issues and concerns of parents to specific information on parent-child communication about topics such as acquired immune deficiency syndrome, nuclear war, and sexuality. Resources are also provided on a large number of topics including suicide, self-esteem, latchkey children, child sexual abuse, child management, the parent's role in the child's education, and alcohol and drug abuse. Bibliographic collections and directories appropriate for parents are listed. The foreword states that a particular parental perspective is not espoused, but rather parents are offered a repertoire of current and relevant resources which if used wisely can lead to more informed choices. It is also noted that this monograph offers a window to the many resources available from the Educational Resources Information Center (ERIC). (ABL)

Seventeen hours of air travel. One crummy rental car. Three generations of headstrong females. And not nearly enough skiing. During a pilgrimage to the mother country, a lot of things [...]

TEENAGERS RUN THE SNOWBLOWERS. Grade-school kids shovel off the tables and walkways. Come summer, they rake the rocks. And the best part? They don't have wifi. Sound like a far [...]

In the 20th century, the advent of neuroimaging dramatically altered the field of neurologic care. However, despite iterative advances since the invention of CT and MRI, little progress has been made to bring MR neuroimaging to the point of care. Recently, the emergence of a low-field (<1 T) portable MRI (pMRI) is setting the stage to revolutionize the landscape of accessible neuroimaging. Users can transport the pMRI into a variety of locations, using a standard 110–220 V wall outlet. In this article, we discuss current applications for pMRI, including in the acute and critical care settings, the barriers to broad implementation, and future opportunities.

To evaluate the prevalence and impact of cognitive impairment on health‐related‐quality of life (HRQoL) in patients with systemic lupus erythematosus (SLE) and neuropsychiatric (NP) symptoms. Patients with SLE and NP symptoms referred to the Leiden NPSLE clinic (2007–2019) were included. In a multidisciplinary evaluation, NP symptoms were attributed to SLE (NPSLE: inflammatory, ischemic, or both combined) or other causes. Four cognitive domains were determined: global cognitive function (score 0–30), learning and memory, executive function and complex attention, and psychomotor speed (all T scores). HRQoL was determined using the mental component score and physical component score of the Short Form 36 health survey. The associations between cognition and NPSLE phenotype and cognition and HRQoL were assessed with multiple regression analyses and linear mixed models corrected for confounding and expressed in SDs. A total of 357 patients (86% female, mean age 44 years) were included. Of those 357 patients, 169 had a follow‐up visit (median follow‐up 11 months). Impairment in global cognitive function was present in 8% of patients, and in all other cognitive domains in ±50%. The most severe impairment (all domains) was seen in patients with a combined NPSLE phenotype. Diffuse cognitive impairment (learning and memory, executive function and complex attention, and psychomotor speed) was most common and was present more often in patients with an inflammatory phenotype. A weak association between cognition and HRQoL was found both cross‐sectionally and longitudinally. In general, 1 SD lower scores on the cognitive domains were associated with at most one‐fifth SD lower HRQoL. Objective cognitive impairment is common in SLE patients with NP symptoms, but may have a limited influence on HRQoL.

Nonsense mutations are responsible for around 10% of cases of genetic diseases, including cystic fibrosis. 2,6-diaminopurine (DAP) has recently been shown to promote efficient readthrough of UGA premature stop codons. In this study, we show that DAP can correct a nonsense mutation in the Cftrgene in vivoin a new CF mouse model, in utero, and through breastfeeding, thanks, notably, to adequate pharmacokinetic properties. DAP turns out to be very stable in plasma and is distributed throughout the body. The ability of DAP to correct various endogenous UGA nonsense mutations in the CFTRgene and to restore its function in mice, in organoids derived from murine or patient cells, and in cells from patients with cystic fibrosis reveals the potential of such readthrough-stimulating molecules in developing a therapeutic approach. The fact that correction by DAP of certain nonsense mutations reaches a clinically relevant level, as judged from previous studies, makes the use of this compound all the more attractive.

IS THERE SUCH A THING AS INEXPENSIVE STICKS THAT RIP? YES, AND THESE 12 PAIRS FIT THE BILL WITH PERFORMANCE AND CASH TO SPARE. There are two truths in skiing: [...]

'I'm very thankful for that spot,' Trevor Kennison, age 27, says into the phone via FaceTime. He's sitting in his car in front of his home resort of Winter Park, [...]

In recent years, several studies have shown what some might intuitively know: having women on the board of directors is beneficial to corporations. But despite mounting evidence in favor of [...]

LIGHTEST Dynafit Blacklight 95 $750 | 6 lbs. 6 oz. (172 cm) | four lengths If you like to set your alarm for an ungodly hour and count every gram, [...]

•What is the primary question addressed by this study?Can cerebral small vessel disease (CSVD) cause apathy, even when no other symptoms of CSVD are present yet?•What is the main finding of this study?A causal relationship between CSVD and apathy was established, but the specificity of this relationship is low.•What is the meaning of the finding?When a CSVD patient presents with apathy we recommend looking for other contributing factors, such as depression or cognitive deterioration.

Overuse injuries of the ankle and foot are common injuries both in sport and in a work-related context. After clinical assessment, imaging is key for early diagnosis. In this overview article, we focus on imaging techniques, protocols, and imaging findings of overuse injuries of the ankle and foot; we emphasize the important role of structured reporting; and we discuss clinical symptoms, epidemiology, and risk factors in sports and in a work-related context.

Objective Patients with a psychiatric disorder are eligible to request medical assistance in dying (MAID) in a small but growing number of jurisdictions, including the Netherlands and Belgium. In Canada, MAID for mental illness will become possible in 2023. For this request to be granted, most of these jurisdictions demand that the patient is competent in her request, and that the suffering experienced is unbearable and irremediable. Especially the criterion of irremediability is challenging to establish in patients with psychiatric disorders. The aim of this research is to establish what criteria Dutch and Belgian experts agree to be necessary in characterising irremediable psychiatric suffering (IPS) in the context of MAID.Methods A two-round Delphi procedure among psychiatrists with relevant experience.Results Thirteen consensus criteria were established: five diagnostic and eight treatment-related criteria. Diagnostically, the participants deem a narrative description and attention to contextual and systemic factors necessary. Also, a mandatory second opinion is required. The criteria concerning treatment show that extensive biopsychosocial treatment is needed, and the suffering must be present for several years. Finally, in the case of refusal, the participants agree that there are limits to the number of diagnostic procedures or treatments a patient must undergo.Conclusions Consensus was found among a Dutch and Belgian expert group on potential criteria for establishing IPS in the context of MAID. These criteria can be used in clinical decision-making and can inform future procedural demands and research.

Race day for a ski racer can be intense, but the savvy race family - and racer - can separate from the intensity by skiing for the pure fun of it. Dylan has never owned a new pair of race skis; in the ski racing community, it's possible to get hand-me-down or borrowed skis from older racers. Coffee gets poured in the thermos, a hasty lunch is made, followed by a scramble to pack up all the gear strewn around the night before: race skis, trainers, free skis, poles, shin guards, arm guards, race suit, spine protector, gloves, ski boots, toe warmers, hand warmers, zip-off pants, down jacket, team jacket, helmet, goggles, water, lunch. There's a timeline to keep when heli skiing to manage the flow of each group of skiers on a tight rotation of ski, fly, ski, fly. Darren and Dana both grew up taking big ski trips with their families - Darren driving from Texas to Colorado, Utah, or Wyoming to ski, and Dana taking week-long "Wedel" lessons in Europe from the military base in Germany where her dad was stationed. [Extracted from the article]

WELCOME TO THE SPOILS OF OUR EDITORS' SHOPPING SPREES. THIS YEAR, IT PAYS TO BE ON THE 'NICE' LIST {GROMS} 1. LEGO Winter Village Cottage Sure, they need new ski [...]

WANT VS. NEED. IT'S AN IMPORTANT DISTINCTION. But when it comes to new ski gear, sell your car, your cat, your soul if you have to. Because new gear equals [...]

The Horn Dog. Like I'm not gonna order that. I'm standing in line at Headwall Pizza and Dog House at the top of the Bridget gondola, watching the guy behind [...]

HELI-YEAH! >> Hell skiing is the ultimate ski experience. Sure, there are 'heli-quality' mornings at big-vert resorts when the canyon's closed. But if you've got a real powder problem, the [...]

This factsheet considers dropping out of school from the dropout's point of view: reasons for dropping out, life after leaving school, and the dropouts' own evaluation of their decision to leave school. It identifies a dislike of school, low academic achievement, and a desire to work as key reasons for dropping out. Thirteen resource documents are listed. (NB)