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Abstract:Studies of queer temporality, both in Scottish literature and more generally, have emphasised the importance of non-linear time and questions of futurity. Scottish texts of the 1920s, however, present a different view, where the rejection of compulsory heterosexuality, at the very least, is historically situated. J. M. Barrie's Mary Rose (1920) juxtaposes multiple timelines to suggest the possibility of rejecting traditional family and gender relations, while Compton Mackenzie's two portraits of queer life on Capri, Vestal Fire (1927) and Extraordinary Women (1928), present the international community there as located firmly in the past. Both authors specifically posit islands, real or fictional, as places of transformation and exploration. Islands not only have their own time, but a unique relation to questions of sexuality. While Barrie and Mackenzie's texts, when discussed at all, are seen as fundamentally conservative and predominantly read in relation to the authors' biographies, this article suggests that their overlooked status in current conversations about queer literature and history is itself productive. In both geographic and historical setting the works emphasise peripherality and non-integration. They are, following Lauren Berlant's recent work, inconvenient texts, and texts about inconvenience. Taking such texts seriously, and emphasising the value of literature, and lives, that remain outliers, demonstrates new interpretive possibilities for the study of queer Scottish literature.

Trees structure the Earth’s most biodiverse ecosystem, tropical forests. The vast number of tree species presents a formidable challenge to understanding these forests, including their response to environmental change, as very little is known about most tropical tree species. A focus on the common species may circumvent this challenge. Here we investigate abundance patterns of common tree species using inventory data on 1,003,805 trees with trunk diameters of at least 10 cm across 1,568 locations1–6in closed-canopy, structurally intact old-growth tropical forests in Africa, Amazonia and Southeast Asia. We estimate that 2.2%, 2.2% and 2.3% of species comprise 50% of the tropical trees in these regions, respectively. Extrapolating across all closed-canopy tropical forests, we estimate that just 1,053 species comprise half of Earth’s 800 billion tropical trees with trunk diameters of at least 10 cm. Despite differing biogeographic, climatic and anthropogenic histories7, we find notably consistent patterns of common species and species abundance distributions across the continents. This suggests that fundamental mechanisms of tree community assembly may apply to all tropical forests. Resampling analyses show that the most common species are likely to belong to a manageable list of known species, enabling targeted efforts to understand their ecology. Although they do not detract from the importance of rare species, our results open new opportunities to understand the world’s most diverse forests, including modelling their response to environmental change, by focusing on the common species that constitute the majority of their trees.

Understanding what controls global leaf type variation in trees is crucial for comprehending their role in terrestrial ecosystems, including carbon, water and nutrient dynamics. Yet our understanding of the factors influencing forest leaf types remains incomplete, leaving us uncertain about the global proportions of needle-leaved, broadleaved, evergreen and deciduous trees. To address these gaps, we conducted a global, ground-sourced assessment of forest leaf-type variation by integrating forest inventory data with comprehensive leaf form (broadleaf vs needle-leaf) and habit (evergreen vs deciduous) records. We found that global variation in leaf habit is primarily driven by isothermality and soil characteristics, while leaf form is predominantly driven by temperature. Given these relationships, we estimate that 38% of global tree individuals are needle-leaved evergreen, 29% are broadleaved evergreen, 27% are broadleaved deciduous and 5% are needle-leaved deciduous. The aboveground biomass distribution among these tree types is approximately 21% (126.4 Gt), 54% (335.7 Gt), 22% (136.2 Gt) and 3% (18.7 Gt), respectively. We further project that, depending on future emissions pathways, 17–34% of forested areas will experience climate conditions by the end of the century that currently support a different forest type, highlighting the intensification of climatic stress on existing forests. By quantifying the distribution of tree leaf types and their corresponding biomass, and identifying regions where climate change will exert greatest pressure on current leaf types, our results can help improve predictions of future terrestrial ecosystem functioning and carbon cycling.

ABSTRACTStories of beachcombing and mudlarking often emphasise the thrill of discovery. While plastic detritus is often taken as a metonym of human-caused pollution, beachcombing texts frequently juxtapose fears for the future with more personal insights and foreground the importance of individual experience in shaping environmental consciousness. Recent illustrated non-fiction by Lara Maiklem, Tracey Williams, and Lisa Woollett, ranging from picture books and field guides to memoir, also highlights the importance of the page as a textual environment. These works use a variety of typographic and illustrative approaches not only to describe beachcombing activities, but to encourage readers’ engagement with the text. Examining these texts in relation to both textual scholarship and philosophical theories of interaction and constellation highlights the complex role of the printed page in introducing readers of all ages to a variety of environmental concerns.

The tropical forest carbon sink is known to be drought sensitive, but it is unclear which forests are the most vulnerable to extreme events. Forests with hotter and drier baseline conditions may be protected by prior adaptation, or more vulnerable because they operate closer to physiological limits. Here we report that forests in drier South American climates experienced the greatest impacts of the 2015–2016 El Niño, indicating greater vulnerability to extreme temperatures and drought. The long-term, ground-measured tree-by-tree responses of 123 forest plots across tropical South America show that the biomass carbon sink ceased during the event with carbon balance becoming indistinguishable from zero (−0.02 ± 0.37 Mg C ha−1per year). However, intact tropical South American forests overall were no more sensitive to the extreme 2015–2016 El Niño than to previous less intense events, remaining a key defence against climate change as long as they are protected.

Tropical forests face increasing climate risk1,2, yet our ability to predict their response to climate change is limited by poor understanding of their resistance to water stress. Although xylem embolism resistance thresholds (for example, Ψ50) and hydraulic safety margins (for example, HSM50) are important predictors of drought-induced mortality risk3–5, little is known about how these vary across Earth’s largest tropical forest. Here, we present a pan-Amazon, fully standardized hydraulic traits dataset and use it to assess regional variation in drought sensitivity and hydraulic trait ability to predict species distributions and long-term forest biomass accumulation. Parameters Ψ50and HSM50vary markedly across the Amazon and are related to average long-term rainfall characteristics. Both Ψ50and HSM50influence the biogeographical distribution of Amazon tree species. However, HSM50was the only significant predictor of observed decadal-scale changes in forest biomass. Old-growth forests with wide HSM50are gaining more biomass than are low HSM50forests. We propose that this may be associated with a growth–mortality trade-off whereby trees in forests consisting of fast-growing species take greater hydraulic risks and face greater mortality risk. Moreover, in regions of more pronounced climatic change, we find evidence that forests are losing biomass, suggesting that species in these regions may be operating beyond their hydraulic limits. Continued climate change is likely to further reduce HSM50in the Amazon6,7, with strong implications for the Amazon carbon sink.

BackgroundThe utility of electronic cigarettes (‘e-cigarettes’) as a smoking cessation adjunct remains unclear. Similarly, it is unclear if formal tobacco treatment (pharmacotherapy and/or behavioural support) augments smoking cessation in individuals who use both cigarettes and e-cigarettes.MethodsWe performed a longitudinal cohort study of adult outpatients evaluated in our tertiary care medical centre (6/2018–6/2020). E-cigarette use, smoking status and formal tobacco treatment (deterrent pharmacotherapy and/or behavioural support) were assessed in 6-month blocks (eg, cohort 1 (C1)=6/2018–12/2018, C2=1/2019–6/2019 and so on) using our electronic health record. We assessed the relationship between e-cigarette use (either with or without formal tobacco treatment) and point prevalence of smoking cessation at 6 and 12 months.Results111 823 unique patients were included in the study. The prevalence of dual use of cigarettes and e-cigarettes increased significantly over the study period (C1=0.8%; C2=1.1%; C3=1.8%; C4=2.3%; p<0.001). The prevalence of smoking cessation at 12 months was higher among e-cigarette users (20.8%) compared with non-users (16.8%) (risk difference, 4.0% (95% CI 2.5% to 5.5%); adjusted relative risk (aRR) 1.354, 95% CI 1.252 to 1.464, p<0.0001). Further, among dual users of cigarettes and e-cigarettes, the prevalence of smoking cessation at 12 months was higher among individuals who received tobacco treatment (29.1%) compared with individuals who did not receive tobacco treatment (19.6%) (risk difference, 9.5% (95% CI, 4.6% to 14.4%); aRR 1.238, 95% CI 1.071 to 1.432, p=0.004).InterpretationThese results suggest that dual users of cigarettes and e-cigarettes benefit from formal tobacco treatment. Clinicians should consider offering formal tobacco treatment to such patients, though future trials are needed.

Forests are a substantial terrestrial carbon sink, but anthropogenic changes in land use and climate have considerably reduced the scale of this system1. Remote-sensing estimates to quantify carbon losses from global forests2–5are characterized by considerable uncertainty and we lack a comprehensive ground-sourced evaluation to benchmark these estimates. Here we combine several ground-sourced6and satellite-derived approaches2,7,8to evaluate the scale of the global forest carbon potential outside agricultural and urban lands. Despite regional variation, the predictions demonstrated remarkable consistency at a global scale, with only a 12% difference between the ground-sourced and satellite-derived estimates. At present, global forest carbon storage is markedly under the natural potential, with a total deficit of 226 Gt (model range = 151–363 Gt) in areas with low human footprint. Most (61%, 139 Gt C) of this potential is in areas with existing forests, in which ecosystem protection can allow forests to recover to maturity. The remaining 39% (87 Gt C) of potential lies in regions in which forests have been removed or fragmented. Although forests cannot be a substitute for emissions reductions, our results support the idea2,3,9that the conservation, restoration and sustainable management of diverse forests offer valuable contributions to meeting global climate and biodiversity targets.

Determining the drivers of non-native plant invasions is critical for managing native ecosystems and limiting the spread of invasive species1,2. Tree invasions in particular have been relatively overlooked, even though they have the potential to transform ecosystems and economies3,4. Here, leveraging global tree databases5–7, we explore how the phylogenetic and functional diversity of native tree communities, human pressure and the environment influence the establishment of non-native tree species and the subsequent invasion severity. We find that anthropogenic factors are key to predicting whether a location is invaded, but that invasion severity is underpinned by native diversity, with higher diversity predicting lower invasion severity. Temperature and precipitation emerge as strong predictors of invasion strategy, with non-native species invading successfully when they are similar to the native community in cold or dry extremes. Yet, despite the influence of these ecological forces in determining invasion strategy, we find evidence that these patterns can be obscured by human activity, with lower ecological signal in areas with higher proximity to shipping ports. Our global perspective of non-native tree invasion highlights that human drivers influence non-native tree presence, and that native phylogenetic and functional diversity have a critical role in the establishment and spread of subsequent invasions.

A new chapter in United States (US) and Mexico energy cooperation opened when President Obama signed the Bipartisan Budget Act, Pub. L. No. 113-67, 127 Stat. 1165 (2013) (Budget Act), [...]

Objective: The aim of this study was to evaluate the cost-utility of nivolumab plus ipilimumab (NIVO + IPI) versus other first-line therapies for advanced melanoma in the United States (US) from the third-party payer perspective. Methods: This analysis estimated total expected life-years (LYs), quality-adjusted LYs (QALYs), and costs for first-line treatments of advanced melanoma during a 30-year time horizon using indirect treatment comparisons based on time-varying hazard ratios (HRs) and a three-state partitioned survival model. Overall survival (OS) and progression-free survival reference curves were extrapolated based on 5-year follow-up from the phase III Checkmate 067 trial (NCT01844505). Comparators of NIVO + IPI were NIVO, IPI, pembrolizumab, dabrafenib plus trametinib, encorafenib plus binimetinib (ENCO + BINI), and vemurafenib plus cobimetinib. Drug acquisition costs, treatment administration costs, follow-up time, subsequent therapy data, and adverse event frequencies were obtained from published sources. Utility weights were estimated from Checkmate 067, which compared NIVO + IPI or NIVO monotherapy with IPI monotherapy as first-line therapy in advanced melanoma. A 3% annual discount rate was applied to costs and outcomes. Sensitivity scenarios for BRAF-mutant subgroups were conducted. Results: NIVO + IPI was estimated to generate the longest OS and the highest total costs versus all comparators, accruing 6.99 LYs, 5.70 QALYs, and $469,469 over the 30-year time horizon. The incremental cost utility of NIVO + IPI versus comparators ranged from $2130 per QALY (versus ENCO + BINI) to $76,169 per QALY (versus NIVO). In all base-case and most sensitivity analyses, the incremental cost-utility ratios for NIVO + IPI were below $100,000 per QALY. Conclusions: NIVO + IPI is estimated to be a life-extending and cost-effective treatment versus other therapies in the US, with base-case incremental cost-utility ratios below $100,000 per QALY.

Tropical peatlands are among the most carbon-dense ecosystems but land-use change has led to the loss of large peatland areas, associated with substantial greenhouse gas emissions. To design effective conservation and restoration policies, maps of the location and carbon storage of tropical peatlands are vital. This is especially so in countries such as Peru where the distribution of its large, hydrologically intact peatlands is poorly known. Here field and remote sensing data support the model development of peatland extent and thickness for lowland Peruvian Amazonia. We estimate a peatland area of 62,714 km2(5th and 95th confidence interval percentiles of 58,325 and 67,102 km2, respectively) and carbon stock of 5.4 (2.6–10.6) PgC, a value approaching the entire above-ground carbon stock of Peru but contained within just 5% of its land area. Combining the map of peatland extent with national land-cover data we reveal small but growing areas of deforestation and associated CO2emissions from peat decomposition due to conversion to mining, urban areas and agriculture. The emissions from peatland areas classified as forest in 2000 represent 1–4% of Peruvian CO2forest emissions between 2000 and 2016. We suggest that bespoke monitoring, protection and sustainable management of tropical peatlands are required to avoid further degradation and CO2emissions.

Smoking cessation results in improved cancer treatment outcomes. However, the factors associated with successful implementation of cessation programs in cancer care settings are not well understood. This paper presents the reach the reach and effectiveness of cessation programs implemented in NCI-Designated Cancer Centers in the Cancer Center Cessation Initiative (C3I). An observational, cross-sectional study was conducted among C3I Cancer Centers from July 1, 2019 and December 31, 2019 (N= 38). Reach was calculated as the proportion of patients reporting current smoking that received cessation treatment and was analyzed overall and by organizational characteristics. Smoking abstinence rates were determined by the proportion of participants self-reporting smoking abstinence in the previous 7 and 30 days at 6 months after treatment. On average, nearly 30% of patients who smoked received any cessation treatment. In-person counseling was most implemented but reached an average of only 13.2% of patients who smoked. Although less frequently implemented, average reach was highest for counseling provided via an interactive voice response system (55.8%) and telephone-based counseling (18.7%). Reach was higher at centers with more established programs, electronic health record referral systems, and higher smoking prevalence. At 6-month follow-up, about a fifth of participants on average had not smoked in the past 7 days (21.7%) or past 30 days (18.6%). Variations in reach by organizational characteristics suggest that leadership engagement and investment in technology-facilitated programs may yield higher levels of reach. Understanding which implementation and intervention strategies facilitate greater cessation treatment reach and effectiveness could lead to improved outcomes among cancer patients who smoke.Smoking cessation programs within 38 Cancer Centers reached 30% of patients, on average, with the greatest reach achieved at more established programs and those with EHR-based referral systems

With veterans coming home with a more serious array of injuries than ever, the Brooke Army Medical Center has responded with pool therapy, a domed simulator to create virtual environments [...]

The use of Ultra Performance Liquid Chromatography (UPLC[TM]) with UV and MS detection was evaluated in several pharmaceutical applications. Initial studies characterized the commercial instrumentation performance parameters for isocratic and [...]

Background: The Agency for Healthcare Research and Quality (AHRQ) Smoking Cessation Clinical Practice Guideline recommends that all clinicians strongly advise their patients who use tobacco to quit. Methods: We conducted a randomized, controlled trial of the effectiveness of Guideline implementation at eight community-based primary care clinics in southern Wisconsin (four test sites, four control sites) among 2163 consecutively enrolled adult patients who smoked at least one cigarette per day and presented for nonemergency care during the baseline period (June 16, 1999, to June 20, 2000) or the intervention period (from June 21, 2000, to May 3, 2001). After collecting baseline data, staff at test sites implemented the intervention over a 2-month period. The intervention included a tutorial for intake clinicians, group and individual performance feedback for intake clinicians, use of a modified vital signs stamp, an offer of free nicotine replacement therapy, and proactive telephone counseling. Staff at control sites received only general information about the AHRQ Guideline. Self-reported abstinence from smoking was determined by telephone interviews at 2-and 6-month follow-up assessments. Hierarchical logistic regression models were used to estimate the odds ratios (ORs) for treatment assignment after adjustment for patient characteristics. All statistical tests were two-sided. Results: There were no statistically significant differences in smoking cessation rates between participants at test and control sites during the baseline period. Among participants treated during the intervention period, those at test sites were more likely than those at control sites to report being abstinent at the 2-month (16.4% versus 5.8%; adjusted OR = 3.3, 95% confidence interval [CI] = 1.9 to 5.6; P

The world’s largest tropical peatland complex is found in the central Congo Basin. However, there is a lack of in situ measurements to understand the peatland’s distribution and the amount of carbon stored in it. So far, peat in this region has been sampled only in largely rain-fed interfluvial basins in the north of the Republic of the Congo. Here we present the first extensive field surveys of peat in the Democratic Republic of the Congo, which covers two-thirds of the estimated peatland area, including from previously undocumented river-influenced settings. We use field data from both countries to compute the first spatial models of peat thickness (mean 1.7 ± 0.9 m; maximum 5.6 m) and peat carbon density (mean 1,712 ± 634 MgC ha−1; maximum 3,970 MgC ha−1) for the central Congo Basin. We show that the peatland complex covers 167,600 km2, 36% of the world’s tropical peatland area, and that 29.0 PgC is stored below ground in peat across the region (95% confidence interval, 26.3–32.2 PgC). Our measurement-based constraints give high confidence of globally significant peat carbon stocks in the central Congo Basin, totalling approximately 28% of the world’s tropical peat carbon. Only 8% of this peat carbon lies within nationally protected areas, suggesting its vulnerability to future land-use change.

Medical students are at a disproportionate risk for experiencing burnout, making management of burnout a critical skill to teach in medical education. If left unmanaged, students may develop maladaptive coping strategies as well as substance misuse, suicidal ideation, and poorer quality patient care. This study examined the impact of Acceptance and Commitment Training (ACT) as a burnout management curriculum with medical students at a western U.S. medical school. Participants (n = 281) completed measures pertaining to psychological flexibility (i.e., the Acceptance and Action Questionnaire-II; AAQ-II) and burnout (i.e., the Implicit Relational Assessment Procedure; IRAP). Assessments were collected at three time points over the first two years of medical school. ACT was provided between Time 1 and 2, and not between Time 2 and 3. Results demonstrated statistically significant improvements, specifically for students starting medical school with clinically relevant levels of distress on the AAQ-II (n = 53). Positivity bias and negativity bias were measured with a burnout themed Modified-IRAP (MD-IRAP). Positivity bias maintained across all three time points, despite an increase in negativity bias. Implications for teaching psychological flexibility as a burnout management tool in higher education and healthcare systems will be discussed.

Supplemental Digital Content is available in the text.

Meaningfully improved mental and behavioral health treatment is an unrealized dream. Across three factorial experiments, inferential tests in prior studies showed a pattern of negative interactions, suggesting that better clinical outcomes may be obtained when participants receive fewer rather than more intervention components. Furthermore, relatively few significant main effects were found in these experiments. Modeling suggested that negative interactions among components may account for these patterns. In this article, we evaluate factors that may contribute to such declining benefit: increased attentional or effort burden; components that produce their effects via the same capacity-limited mechanisms, making their effects subadditive; and a tipping-point phenomenon in which people near a hypothesized tipping point for change will benefit markedly from weak intervention and people far from the tipping point will benefit little from even strong intervention. New research should explore factors that cause negative interactions among components and constrain the development of more effective treatments.

Kate Haffey has recently argued that if queer time can be seen as a turning away from narrative coherence, it suggests new possibilities for considering narrative structures more generally. Combining the narratively rigid structures of the school story and the detective novel, the four novels discussed in this article – Gladys Mitchell’s Laurels are Poison(1942), Josephine Tey’s Miss Pym Disposes(1946), Shirley Jackson’s Hangsaman(1951), and Joan Lindsay’s Picnic at Hanging Rock(1967) – disrupt conventional understandings of linear time. Depicting not only queer, or potentially queer, characters, but a queer phenomenological perspective, they challenge reader expectations with a focus on aporias and gaps, whether in terms of trauma (Jackson), the blurring of fact and fiction (Lindsay), or the prolonged delay of both crime and resolution (Tey). These novels draw attention to the insufficiency of texts to capture experience, and the inadequacy of textual authority. As such, they reveal the extent to which mid-twentieth-century women’s fiction was able to challenge the genres and narrative structures with which it was most closely associated.

Objective: To assess the effectiveness of transdermal nicotine therapy for smoking cessation and suppression of withdrawal severity in conjunction with two different adjuvant counseling treatments. Design: Two independent randomized placebo-controlled [...]

Background. This study applies the concept of economic efficiency to primary health care physicians. Comparisons of charges made by family physicians and general internists would provide evidence of "optimal" health care delivery of primary care services. Methods. A list of all active licensed primary care physicians was obtained from the office of the Oregon State Board of Medical Examiners. Two thousand eight hundred forty-three questionnaires were sent to Oregon primary care physicians. Of the 1365 responses, 484 were family physicians and 341 were general internists. Results. The study found that family physicians had significantly lower mean office visit fees than general internists, while both groups had essentially similar patient mixes. This difference in fees could not be explained by patient case mix. Conclusions. The findings of this study and the body of literature available support the concept that family practice physicians provide economically efficient primary health care. If two similarly trained physicians provide a comparable level of medical care, with the same or similar outcome (or output), the physician who provides the care for the lowest cost should be used. Key words. Fees and charges; charge differentials; economics, medical; family practice fees; internal medicine fees. (J Fam Pract 1993; 37:35-43), Changes in economic conditions over the past 10 years have caused new concerns about the high costs of health care.[1,2] The United States now spends approximately 12% of its gross [...]

A look at the evolution of shopping mall design, including HVA design criteria, tenant fitup, tie-ins with fire protection system, and startup and testing of life safety system In 1975, [...]

Micelles were prepared from polymer-peptide block copolymer amphiphiles containing substrates for protein kinase A, protein phosphatase-1, and matrix metalloproteinases 2 and 9. We examine reversible switching of the morphology of these micelles through a phosphorylation−dephosphorylation cycle and study peptide-sequence directed changes in morphology in response to proteolysis. Furthermore, the exceptional uniformity of these polymer-peptide particles makes them amenable to cryo-TEM reconstruction techniques lending insight into their internal structure.

The development in the past decade of both unmanned aerial systems, or drones, and near infrared camera technology has significantly augmented the use of remote sensing in agriculture. The increased consumer availability, rapid deployment, and simple operation of drones when partnered with the smaller size and high resolution of imagery obtained by newer near infrared cameras makes them an ideal tool for obtaining very current assessments of crop health and pest status in crops. We discuss some of the potential uses and successful applications of these technologies in scouting for insects in potato.

Tobacco smoking is an important risk factor for cancer incidence, an effect modifier for cancer treatment, and a negative prognostic factor for disease outcomes. Inadequate implementation of evidence-based smoking cessation treatment in cancer centers, a consequence of numerous patient-, provider-, and system-level barriers, contributes to tobacco-related morbidity and mortality. This study provides data for a paradigm shift from a frequently used specialist referral model to a point-of-care treatment model for tobacco use assessment and cessation treatment for outpatients at a large cancer center. The point-of-care model is enabled by a low-burden strategy, the Electronic Health Record-Enabled Evidence-Based Smoking Cessation Treatment program, which was implemented in the cancer center clinics on June 2, 2018. Five-month pre- and post-implementation data from the electronic health record (EHR) were analyzed. The percentage of cancer patients assessed for tobacco use significantly increased from 48% to 90% (z = 126.57, p < .001), the percentage of smokers referred for cessation counseling increased from 0.72% to 1.91% (z = 3.81, p < .001), and the percentage of smokers with cessation medication significantly increased from 3% to 17% (z = 17.20, p < .001). EHR functionalities may significantly address barriers to point-of-care treatment delivery, improving its consistent implementation and thereby increasing access to and quality of smoking cessation care for cancer center patients.

Too few smokers who present for outpatient healthcare receive evidence-based interventions to stop smoking. Referral to nationally available smoking cessation support may enhance tobacco intervention reach during healthcare visits. This study evaluated the feasibility of outpatient electronic health record (EHR)-enabled, closed-loop referral (eReferral) to SmokefreeTXT, a National Cancer Institute text message smoking cessation program. SmokefreeTXT eReferral for adult patients who smoke was implemented in a family medicine clinic and an allergy and asthma clinic in an integrated Midwestern healthcare system. Interoperable, HIPAA-compliant eReferral returned referral outcomes to the EHR. In Phase 1 of implementation, clinicians were responsible for eReferral; in Phase 2 this responsibility shifted to Medical Assistants and/or nurses. EHR data were extracted to compute eReferral rates among adult smokers and compare demographics among those eReferred versus not referred. SmokefreeTXT data were used to compute SmokefreeTXT enrollment rates among those eReferred. Descriptive analyses of clinic staff surveys assessed implementation context and staff attitudes toward and adaptations of eReferral processes. During clinician implementation, 43 of 299 adult smokers (14.4%) were eReferred. During medical assistant (MA) implementation, 36 of 401 adult smokers (9.0%) were eReferred. Overall, among those eReferred, 25.7% completed SmokefreeTXT enrollment (3.1% of patients eligible for eReferral). Staff survey responses indicated that eReferral was efficient and easy. eReferral rates and relevant attitudes varied meaningfully by clinic. Thus, interoperable eReferral via outpatient EHR to SmokefreeTXT is feasible and acceptable to clinic staff and enrolls roughly 3.0% of smokers. Clinic context and implementation approach may influence reach.

AbstractAimsThe objective of this study was to evaluate the cost-effectiveness of nivolumab in combination with ipilimumab (nivo + ipi) compared to current therapeutic alternatives in first-line treatment of patients with advanced melanoma from the Japanese national healthcare payer perspective using 48-month survival data from the CheckMate 067 Phase III trial.Materials and methodsA three-state partitioned survival model was developed from projections of overall survival (OS) and progression-free survival (PFS) to estimate accrued quality-adjusted survival and costs over a 30-year time horizon. The analysis included nivo + ipi, nivolumab, and ipilimumab monotherapies (the three treatments included in CheckMate 067). Drug acquisition, administration, disease management, subsequent therapy, and adverse event (AE) costs were obtained via published sources and expert input (solicited via Delphi panel). AE frequencies were collected from the Checkmate 067 trial. Utility weights were estimated from the Checkmate 067 trial, based on Japanese tariffs. Results were presented as incremental cost-utility ratios (ICURs, cost per quality-adjusted life-year (QALY)).ResultsNivo + ipi had the greatest estimated survival among the three competing treatments, followed by nivolumab monotherapy accruing the second greatest survival. The incremental cost-effectiveness of nivo + ipi was ¥778,000 per QALY vs. nivolumab and ¥1,584,000 per QALY vs. ipilimumab. The results indicate that nivo + ipi is cost-effective in Japan when compared to a threshold of ¥7,500,000 per QALY. This finding was found to be generally robust to sensitivity and scenario analyses.LimitationsLimitations include uncertainty in long-term survival extrapolations and lack of Japan-specific clinical data.ConclusionsThis analysis indicates that adding ipilimumab to nivolumab therapy represents a cost-effective new treatment option for patients with unresectable malignant melanoma in Japan.

This case study explores the scaling experience of an early‐stage healthtech startup company called myICUvoice. During the Covid‐19 pandemic, myICUvoice rapidly scaled from a single intensive care environment to being widely used nationally (UK) as well as globally. We explore whyand howso many volunteers were motivated to donate their time and expertise to help scale this early stage startup. Specifically, we examine the roles that empathy played throughout the scaling process. There are three distinct types of empathy that we have identified in our story: em‐pathos, empathetic understanding, and mass‐empathy. These each had a distinct role in driving the startup forward. Importantly, we note that human‐centered design (which often focuses almost exclusively on achieving empathetic understanding) will immensely benefit from considering the multiple types, and multi‐faceted powers, of empathy.

Structurally intact tropical forests sequestered about half of the global terrestrial carbon uptake over the 1990s and early 2000s, removing about 15 per cent of anthropogenic carbon dioxide emissions1–3. Climate-driven vegetation models typically predict that this tropical forest ‘carbon sink’ will continue for decades4,5. Here we assess trends in the carbon sink using 244 structurally intact African tropical forests spanning 11 countries, compare them with 321 published plots from Amazonia and investigate the underlying drivers of the trends. The carbon sink in live aboveground biomass in intact African tropical forests has been stable for the three decades to 2015, at 0.66 tonnes of carbon per hectare per year (95 per cent confidence interval 0.53–0.79), in contrast to the long-term decline in Amazonian forests6. Therefore the carbon sink responses of Earth’s two largest expanses of tropical forest have diverged. The difference is largely driven by carbon losses from tree mortality, with no detectable multi-decadal trend in Africa and a long-term increase in Amazonia. Both continents show increasing tree growth, consistent with the expected net effect of rising atmospheric carbon dioxide and air temperature7–9. Despite the past stability of the African carbon sink, our most intensively monitored plots suggest a post-2010 increase in carbon losses, delayed compared to Amazonia, indicating asynchronous carbon sink saturation on the two continents. A statistical model including carbon dioxide, temperature, drought and forest dynamics accounts for the observed trends and indicates a long-term future decline in the African sink, whereas the Amazonian sink continues to weaken rapidly. Overall, the uptake of carbon into Earth’s intact tropical forests peaked in the 1990s. Given that the global terrestrial carbon sink is increasing in size, independent observations indicating greater recent carbon uptake into the Northern Hemisphere landmass10reinforce our conclusion that the intact tropical forest carbon sink has already peaked. This saturation and ongoing decline of the tropical forest carbon sink has consequences for policies intended to stabilize Earth’s climate.

Many proteins exist naturally as symmetrical homooligomers or homopolymers1. The emergent structural and functional properties of such protein assemblies have inspired extensive efforts in biomolecular design2–5. As synthesized by ribosomes, proteins are inherently asymmetric. Thus, they must acquire multiple surface patches that selectively associate to generate the different symmetry elements needed to form higher-order architectures1,6—a daunting task for protein design. Here we address this problem using an inorganic chemical approach, whereby multiple modes of protein–protein interactions and symmetry are simultaneously achieved by selective, ‘one-pot’ coordination of soft and hard metal ions. We show that a monomeric protein (protomer) appropriately modified with biologically inspired hydroxamate groups and zinc-binding motifs assembles through concurrent Fe3+and Zn2+coordination into discrete dodecameric and hexameric cages. Our cages closely resemble natural polyhedral protein architectures7,8and are, to our knowledge, unique among designed systems9–13in that they possess tightly packed shells devoid of large apertures. At the same time, they can assemble and disassemble in response to diverse stimuli, owing to their heterobimetallic construction on minimal interprotein-bonding footprints. With stoichiometries ranging from [2 Fe:9 Zn:6 protomers] to [8 Fe:21 Zn:12 protomers], these protein cages represent some of the compositionally most complex protein assemblies—or inorganic coordination complexes—obtained by design.

Deregulation and new technologies are removing the geographical boundaries of markets the world over, triggering a trend towards direct cross-border buying and selling. But a number of obstacles will have [...]

The discontinuation of the United States Medical Licensing Examination Step 2 Clinical Skills (CS) in 2020 in response to the COVID-19 pandemic marked the end of a decades-long debate about the utility and value of the exam. For all its controversy, the implementation of Step 2 CS in 2004 brought about profound changes to the landscape of medical education, altering the curriculum and assessment practices of medical schools to ensure students were prepared to take and pass this licensing exam. Its elimination, while celebrated by some, is not without potential negative consequences. As the responsibility for assessing students’ clinical skills shifts back to medical schools, educators must take care not to lose the ground they have gained in advancing clinical skills education. Instead, they need to innovate, collaborate, and share resources; hold themselves accountable; and ultimately rise to the challenge of ensuring that physicians have the necessary clinical skills to safely and effectively practice medicine.

To learn more concerning the causes of death for the approximately 200 US citizens who die in Mexico each year while traveling, a study of death reports was carried out. Death reports constitute proof of death in such cases, and are sent to the US Department of State, Division of Passports. Records from 1975 and 1984 (the last year with complete records) were analyzed. Results showed that 197 US travelers died in Mexico in 1975, and 199 died in 1984. Seventy-four percent of these deaths (for both years) were men. Children younger than 15 and people older than 65 accounted for 12 and 18 percent of the deaths, respectively. A greater proportion of travelers died of injury-related causes than of chronic disease. Mortality was lower for circulatory disease and malignancies in travelers than in US residents not traveling. Travelers had higher death rates from unintentional injury, homicide and suicide than US residents. Male travelers aged 25 and older had similar death rates from motor vehicle crashes to rates of US residents of the same age, but higher death rates due to airplane crashes. Only one death due to infectious disease was reported out of all 396 cases. Overall, the most common cause of death among travelers to Mexico in the years studied was injury, possibly because travelers are exposed to more dangerous situations than people who stay at home. The travel patterns that may contribute to these statistics are discussed. Physicians should be aware that their patients who travel to Mexico are at higher risk of death from injury than from disease. Illness rates, as distinct from mortality, were not explored in the study. (Consumer Summary produced by Reliance Medical Information, Inc.)

Quantifying carbon dynamics in forests is critical for understanding their role in long-term climate regulation1–4. Yet little is known about tree longevity in tropical forests3,5–8, a factor that is vital for estimating carbon persistence3,4. Here we calculate mean carbon age (the period that carbon is fixed in trees7) in different strata of African tropical forests using (1) growth-ring records with a unique timestamp accurately demarcating 66 years of growth in one site and (2) measurements of diameter increments from the African Tropical Rainforest Observation Network (23 sites). We find that in spite of their much smaller size, in understory trees mean carbon age (74 years) is greater than in sub-canopy (54 years) and canopy (57 years) trees and similar to carbon age in emergent trees (66 years). The remarkable carbon longevity in the understory results from slow and aperiodic growth as an adaptation to limited resource availability9–11. Our analysis also reveals that while the understory represents a small share (11%) of the carbon stock12,13, it contributes disproportionally to the forest carbon sink (20%). We conclude that accounting for the diversity of carbon age and carbon sequestration among different forest strata is critical for effective conservation management14–16and for accurate modelling of carbon cycling4.

Aim:This study tests whether polygenic risk scores (PRSs) for nicotine metabolism predict smoking behaviors in independent data. Materials & methods:Linear regression, logistic regression and survival analyses were used to analyze nicotine metabolism PRSs and nicotine metabolism, smoking quantity and smoking cessation. Results:Nicotine metabolism PRSs based on two genome wide association studies (GWAS) meta-analyses significantly predicted nicotine metabolism biomarkers (R2range: 9.2–16; minimum p  7.6 × 10-8). The GWAS top hit variant rs56113850 significantly predicted nicotine metabolism biomarkers (R2range: 14–17; minimum p  4.4 × 10-8). There was insufficient evidence for these PRSs predicting smoking quantity and smoking cessation. Conclusion:Results suggest that nicotine metabolism PRSs based on GWAS meta-analyses predict an individual's nicotine metabolism, so does use of the top hit variant. We anticipate that PRSs will enter clinical medicine, but additional research is needed to develop a more comprehensive genetic score to predict smoking behaviors.

The co-self-assembly of proteins and nucleic acids (NAs) produces complex biomolecular machines (e.g., ribosomes and telomerases) that represent some of the most daunting targets for biomolecular design. Despite significant advances in protein and DNA or RNA nanotechnology, the construction of artificial nucleoprotein complexes has largely been limited to cases that rely on the NA-mediated spatial organization of protein units, rather than a cooperative interplay between protein- and NA-mediated interactions that typify natural nucleoprotein assemblies. We report here a structurally well-defined synthetic nucleoprotein assembly that forms through the synergy of three types of intermolecular interactions: Watson–Crick base pairing, NA–protein interactions, and protein–metal coordination. The fine thermodynamic balance between these interactions enables the formation of a crystalline architecture under highly specific conditions.

•Genomic discoveries can help improve patient care and public health.•Advancing science in precision treatment and precision prevention are important.•Evaluating a genomic marker as a predictor can guide clinical actions.•Genomic medicine can enhance prevention and treatment.

Introduction:The majority of attempts to stop smoking end in failure. One way to improve success may be to explore different combinations of existing cessation medications.Aims:This observational study examined ‘triple therapy’ (varenicline + nicotine patch + nicotine lozenge) in 36 smokers trying to quit.Methods:A 12-week, observational study exploring tolerability, via adverse events (AEs) elicited at each of nine phone assessments. Secondary outcomes included satisfaction rates, medication changes and self-reported quit rates at week 12.Results:Thirty five of thirty six participants reported at least one AE. Insomnia (75%), abnormal dreams (72%) and nausea (64%) were most common. Most were mild to moderate. No deaths, hospitalisations, cardiovascular events or suicidality were reported. Six participants (17%) decreased the dose of at least one medication, 5 (14%) decreased the dose then discontinued at least one medication and 13 (36%) discontinued at least one medication without trying a lesser dose. Participants were highly satisfied with their medications, and 58% reported quitting at 12 weeks, with 38% reporting prolonged abstinence.Conclusions:Despite high rates of AEs and medication changes, high rates of satisfaction and self-reported quitting, with no serious AEs, were observed with triple therapy. Additional data on tolerability and efficacy are needed.Trial Registration:Clinicaltrials.govnumber NCT02681510.