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The Middle Period of the Atacama oases, North Chile, has been characterized as a time of peace, uniform abundance, and widespread access to exotic materials. In the present work, we test this notion through a comparison of Middle Period human isotopic data (δ13Cco, δ15Nco, and δ13Cap) representing two distinct ayllus, Solcor and Tchecar, in the San Pedro de Atacama oases. We employ Bayesian mixture modeling of individual-level isotopic data to quantify and compare dietary composition within and between the cemetery populations of these two contemporary locales. Ultimately, our research shows that dietary diversity, which we take as a proxy for differential levels of participation in long-distance exchange or the access to the products thereof, was unequally distributed, and that the supposedly uniform richness of the Middle Period was similarly discontinuous. While average isotopic values for the two ayllus were similar, variance within each differed significantly, as did variance in dietary composition arrived at through modeling. By all measures, the individuals interred in Solcor 3 had more varied diets, particularly in terms of carbohydrate-rich plants, than their contemporaries interred at Tchecar Túmulo Sur, suggesting that more individuals from Solcor 3 had greater participation in/access to long-distance exchange networks. Besides providing novel insights into the lived experience of the Middle Period residents of far northern Chile, this work also demonstrates the power of Bayesian mixture modeling for the reconstruction of individual paleodiet.

Although the association between in utero exposure to diethylstilbestrol (DES) and clear cell adenocarcinoma of the cervix and vagina (CCA) was first reported among young women, subsequent case reports and cohort studies suggest that an elevated risk for CCA may persist with age. Data from the National Program of Cancer Registries (NPCR) and the Surveillance, Epidemiology and End Results (SEER) Program were used to construct indirect standardized incidence ratios (SIR) comparing CCA risk among women born during the exposure period 1947 through 1971, when DES was prescribed to pregnant women, to the relevant time period for nonexposed women born before or after DES exposure period. CCA incidence among the women born before the DES exposure period (ages 30-54 at diagnosis of CAA) or after the DES exposure period (ages 15-29 at diagnosis) were used to calculate the expected rates for women born during the DES exposure period. Among women aged 15-29 years, CCA risk increased with age and peaked in the 25-29 year age group, but the risk estimates were unstable (SIR = 6.06; 95% CI: 0.97, -251.07, SEER data). Among women aged 40-54 years, CCA risk was greatest in the 40-44 year age group (SIR = 4.55; 95% CI: 1.11, 40.19, SEER data and SIR = 3.94; 95% CI: 1.06, 33.01, NPCR/SEER data) and remained significantly elevated throughout this age group in the combined data set. Risk was not elevated among women aged 30-39 years. The observed risk of CCA, if causally related to DES exposure, reflects a persistent health impact from in utero exposure that is widespread in the general population. When assessing a woman's cancer risks, whether her mother took DES while pregnant may still be a relevant aspect of the medical history for women born during the period of DES use in pregnancy. [ABSTRACT FROM AUTHOR]

Background: Degenerative cervical myelopathy (DCM) is a progressive neurological condition, characterized by spinal cord injury secondary to degenerative changes in the spine. Misdiagnosis in primary care forms part of a complex picture leading to an average diagnostic delay of 2 years. This leads to potentially preventable and permanent disability. A lack of awareness secondary to deficits in postgraduate education may contribute to these delays., Objective: This study aims to assess the awareness of DCM in the setting of general practice., Methods: General practitioners completed a quantitative web-based cross-sectional questionnaire. The 17-item questionnaire captured data regarding demographics, subjective awareness, and objective knowledge. The questionnaire was disseminated via professional networks, including via practice managers and senior practice partners. Incentivization was provided via a bespoke DCM fact sheet for those that completed the survey., Results: A total of 54 general practitioners representing all 4 UK nations responded to the survey. General practitioners most commonly self-assessed that they had "limited awareness" of DCM (n=24, 51%). General practitioners felt most commonly "moderately able" to recognize a case of DCM (n=21, 46%). In total, 13% (n=6) of respondents reported that they would not be at all able to recognize a patient with DCM. Respondents most commonly reported that they were "moderately confident" in their ability to triage a patient with DCM (n=19, 41%). A quarter of respondents reported no prior introduction to DCM throughout their medical training (n=13, 25%). The mean score for knowledge-based questions was 42.6% (SD 3.96%) with the lowest performance observed in patient demographic and clinical recognition items., Conclusions: General practitioners lack confidence in the recognition and management of DCM. These findings are consistent with the diagnostic delays previously described in the literature at the primary care level. Further work to develop and implement educational interventions to general practitioner practices is a crucial step to improving patient outcomes in DCM., (©Remi M Rufus-Toye, Amir Rafati Fard, Oliver D Mowforth, Luke V McCarron, Kayen Chan, Yuri Hirayama, Emma K Smith, Munashe Veremu, Benjamin M Davies, Jamie F M Brannigan. Originally published in JMIR Formative Research (https://formative.jmir.org), 19.08.2024.)

Further research is urgently needed to address the disproportionately high rates of eating disorders (EDs) among transgender, gender diverse, and intersex (TGDI) individuals in comparison to cisgender, endosex (non-intersex) populations. As TGDI advocates, academics, and clinicians with lived/living experience with EDs, we propose a set of recommendations to guide ethical research specifically about EDs and disordered eating behaviors in TGDI populations. The guidelines included here aim to educate non-TGDI researchers and support TGDI researchers seeking to carry out such research. Considerations for study design, planning, data collection, and dissemination are included.

Background: Left atrial appendage exclusion (LAAE) is an effective alternative to long-term anticoagulation in patients with atrial fibrillation. Not all patients considered for LAAE undergo the procedure because of ineligibility, anatomic or medical constraints, and preference of the patient., Objective: The objective of this study was to report on the management strategies and long-term clinical outcomes of patients referred to a dedicated multidisciplinary LAAE clinic, including all who subsequently did and did not undergo LAAE., Methods: This was a retrospective analysis of prospectively acquired data from all patients referred to the comprehensive multidisciplinary LAAE clinic at the University of Michigan between 2016 and 2022. A consecutive 301 patients (age, 75 ± 8 years; 106 women) with atrial fibrillation were evaluated. LAAE was performed in 168 patients (56%) with use of the Watchman device in 146 (49%) and surgically in 22 (7%). LAAE was not performed in 133 patients (44%, no-LAAE group) because of ineligibility in 62 (21%), anatomic constraints in 23 (7%), and preference of the patient in 48 (36%). The CHA 2 DS 2 -VASc score (4.7 ± 1.5 vs 4.1 ± 1.6; P = .002) and HAS-BLED score (3.4 ± 1.0 vs 2.8 ± 1.1; P < .001) were higher in the LAAE groups., Results: Anticoagulant therapy was discontinued in 137 of 146 (94%) and 61 of 133 (61%) in the Watchman and no-LAAE groups, respectively (P < .001). During a median follow-up of 2.2 years (interquartile range, 1.2-4.0 years), in the LAAE (n = 168) and no-LAAE (n = 133) groups, respectively, 39 (23%) vs 29 (22%) deaths, 13 (8%) vs 5 (4%) thromboembolic events, and 24 (14%) vs 23 (17%) bleeding complications occurred. Continued long-term anticoagulation was not a predictor of clinical outcomes., Conclusion: After a comprehensive evaluation in a multidisciplinary clinic, ∼50% of the patients referred for LAAE did not proceed with LAAE and resumed anticoagulation., Competing Interests: Disclosures The authors have no conflicts of interest to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Sexual minority (e.g., gay/lesbian, bisexual, and queer) students are more likely than their heterosexual peers to experience sexual violence (SV) during college. Interventions that prevent SV and improve SV care-seeking behaviors for sexual minority students are lacking. Giving Information for Trauma Support and Safety (GIFTSS) is an evidence-based universal SV intervention implemented by providers during college health and counseling visits. Compared to controls, GIFTSS participants reported greater self-efficacy to use SV harm reduction strategies and SV disclosure during clinical visits. However, GIFTSS' effectiveness for sexual minority participants is unknown. The current study examines whether sexual orientation moderates GIFTSS' effects on numerous SV-related outcomes (i.e., to test whether intervention effects at 4 and 12 months differed based on sexual orientation). Across 28 college campuses in Pennsylvania and West Virginia, 2,291 students participated in a two-arm cluster-randomized controlled trial. We used mixed models with two- and three-way interaction terms to test whether sexual orientation modified GIFTSS' effects at 4- and 12-month follow-up on participants': SV recognition; knowledge of and self-efficacy to enact SV harm reduction strategies; intentions to intervene; knowledge of and self-efficacy to use SV-related services; SV disclosure during visits; and recent SV exposure. Overall, 22.1% of participants were sexual minorities ( n  = 507). Sexual orientation moderated GIFTSS effectiveness as indicated by significant three-way interaction ( p  = .01) at 12-month follow-up, and knowledge of SV services decreased for heterosexual participants (β = -.23) but increased for sexual minority participants (β = .23). Our study indicates that universal provider-based education may promote greater knowledge of SV services among sexual minority than heterosexual participants, and population-specific interventions are needed that reduce sexual minority students' SV exposure, service utilization, and other critical aspects of SV prevention on university campuses. Clinical Trial Registration: Registry name: College Health Center-based Alcohol and Sexual Violence Intervention (GIFTSS), Registration number: NCT02355470, Web link: https://clinicaltrials.gov/ct2/show/NCT02355470, Deidentified individual participant data will not be made available., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Transgender and gender diverse adults, referred to collectively as trans, experience eating disorders (EDs) at high rates and struggle to find primary care providers (PCPs) knowledgeable in both gender-affirming care and EDs. Most research regarding healthcare experiences of trans people with EDs focuses on specialized treatment. This qualitative study explored the experiences of trans patients with ED symptoms in trans-affirming primary care, which offers clinical support for gender affirmation in the context of interpersonally gender-affirming primary care services. Twenty-two participants were recruited via social media to participate in focus groups (n = 5). Researchers utilized thematic analysis. Participants reported gender-affirming and non-affirming experiences, experienced unwelcome comments from providers regarding bodies and gender, encountered barriers to disclosing their ED symptoms, felt transition-related medical care supported recovery but did not always resolve their ED symptoms, felt they had to self-advocate, and wanted their providers to recognize them as whole people (beyond their ED and transness) who experience joy. Importantly, despite being trans-affirming, participants critiqued trans-affirming primary care as perpetuating weight stigma and binary gender norms. Participants recommended providers receive ED training, implement universal ED screening, and explore how sociocultural norms regarding weight and gender negatively impact trans health outcomes., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Expanded international trade and globalised production networks are increasing the environmental and social impacts in middle-income countries (GNI per capita $1,136-$13,845). High-income countries (>$13,845) are seeking to mitigate the negative impacts of domestic consumption by imposing new sustainability regulations on global supply chains. Recent evidence suggests that these regulations are broadly supported across high-income countries. However, it remains unclear whether citizens of middle-income countries support aligning domestic sustainability regulations with the measures developed by high-income countries. Concerns about economic competitiveness and foreign imposition could increase public resistance toward such alignment. Alternatively, desires for continued market access in high-income countries and aspirations for strengthening local environmental and labour regulations could foster support for alignment. Based on survey-embedded experiments in the three largest democratic non-OECD economies (Brazil, India, Indonesia), we find surprisingly strong support for domestic-based measures that are aligned with emerging global supply chain sustainability regulations. Our findings suggest that support is largely driven by positive impact expectations, where the future benefits of alignment are perceived as outweighing concerns about increased costs. These results bode well for initiatives to install stricter sustainability regulations for global supply chains that are acceptable not only in high-income economies but also in non-OECD countries., (© 2024. The Author(s).)

Introduction: AO Spine RECODE-DCM was a multi-stakeholder priority setting partnership (PSP) to define the top ten research priorities for degenerative cervical myelopathy (DCM). Priorities were generated and iteratively refined using a series of surveys administered to surgeons, other healthcare professionals (oHCP) and people with DCM (PwDCM). The aim of this work was to utilise word clouds to enable the perspectives of people with the condition to be heard earlier in the PSP process than is traditionally the case. The objective was to evaluate the added value of word clouds in the process of defining research uncertainties in National Institute for Health Research (NIHR) James Lind Alliance (JLA) Priority Setting Partnerships., Methods: Patient-generated word clouds were created for the four survey subsections of the AO Spine RECODE-DCM PSP: diagnosis, treatment, long-term management and other issues. These were then evaluated as a nested methodological study. Word-clouds were created and iteratively refined by an online support group of people with DCM, before being curated by the RECODE-DCM management committee and expert healthcare professional representatives. The final word clouds were embedded within the surveys administered at random to 50% of participants. DCM research uncertainties suggested by participants were compared pre- and post-word cloud presentation., Results: A total of 215 (50.9%) participants were randomised to the word cloud stream, including 118 (55%) spinal surgeons, 52 (24%) PwDCM and 45 (21%) oHCP. Participants submitted 434 additional uncertainties after word cloud review: word count was lower and more uniform across each survey subsections compared to pre-word cloud uncertainties. Twenty-three (32%) of the final 74 PSP summary questions did not have a post-word cloud contribution and no summary question was formed exclusively on post-word cloud uncertainties. There were differences in mapping of pre- and post-word cloud uncertainties to summary questions, with greater mapping of post-word cloud uncertainties to the number 1 research question priority: raising awareness. Five of the final summary questions were more likely to map to the research uncertainties suggested by participants after having reviewed the word clouds., Conclusions: Word clouds may increase the perspective of underrepresented stakeholders in the research question gathering stage of priority setting partnerships. This may help steer the process towards research questions that are of highest priority for people with the condition., (© 2023. The Author(s).)

Purpose: To investigate the breakfast quality of preschool-aged children through a comparison of their energy and nutrient intakes at breakfast to published benchmarks for a balanced breakfast. Methods: Dietary data were collected for 163 children aged 3-5 years enrolled in the Guelph Family Health Study using one parent-reported online 24-hour recall and analyzed for energy and nutrient intakes. Breakfast quality was assessed by tallying the frequency of participants whose nutrient and energy intakes at their breakfast meal met the recommendations for a balanced breakfast established by the International Breakfast Research Initiative (IRBI). Results: Almost all participants (98%) consumed breakfast, and most participants (82.5%) met the energy IRBI recommendation. However, the majority of participants did not meet the IRBI recommendations for breakfast intakes of most macronutrients and micronutrients. In particular, fewer than 25% of participants met the IRBI recommendations for breakfast intakes of dietary fibre, niacin, folate, vitamin C, calcium, potassium and zinc. Conclusions: Almost all preschool-aged children in this study consumed breakfast, but the nutritional quality of their breakfast did not meet recommendations for most nutrients. These results can inform nutrition education and intervention programs for children that aim to improve the nutritional quality of breakfast.

Background People living with HIV have higher sudden cardiac death (SCD) rates compared with the general population. Whether HIV infection is an independent SCD risk factor is unclear. Methods and Results This study evaluated participants from the Veterans Aging Cohort Study, an observational, longitudinal cohort of veterans with and without HIV infection matched 1:2 on age, sex, race/ethnicity, and clinical site. Baseline for this study was a participant's first clinical visit on or after April 1, 2003. Participants were followed through December 31, 2014. Using Cox proportional hazards regression, we assessed whether HIV infection, CD4 cell counts, and/or HIV viral load were associated with World Health Organization (WHO)-defined SCD risk. Among 144 336 participants (30% people living with HIV), the mean (SD) baseline age was 50.0 years (10.6 years), 97% were men, and 47% were of Black race. During follow-up (median, 9.0 years), 3035 SCDs occurred. HIV infection was associated with increased SCD risk (hazard ratio [HR], 1.14; 95% CI, 1.04-1.25), adjusting for possible confounders. In analyses with time-varying CD4 and HIV viral load, people living with HIV with CD4 counts <200 cells/mm 3 (HR, 1.57; 95% CI, 1.28-1.92) or viral load >500 copies/mL (HR, 1.70; 95% CI, 1.46-1.98) had increased SCD risk versus veterans without HIV. In contrast, people living with HIV who had CD4 cell counts >500 cells/mm 3 (HR, 1.03; 95% CI, 0.90-1.18) or HIV viral load <500 copies/mL (HR, 0.97; 95% CI, 0.87-1.09) were not at increased SCD risk. Conclusions HIV infection is associated with increased risk of WHO-defined SCD among those with elevated HIV viral load or low CD4 cell counts.

Objectives: AO Spine REsearch objectives and Common Data Elements for Degenerative Cervical Myelopathy [RECODE-DCM] is a multi-stakeholder consensus process aiming to promote research efficiency in DCM. It aims to establish the top 10 research uncertainties, through a James Lind Alliance Priority Setting Partnership [PSP]. Through a consensus process, research questions are generated and ranked. The inclusion of people with cervical myelopathy [PwCM] is central to the process. We hypothesized that presenting PwCM experience through word cloud generation would stimulate other key stakeholders to generate research questions better aligned with PwCM needs. This protocol outlines our plans to evaluate this as a nested methodological study within our PSP., Methods: An online poll asked PwCM to submit and vote on words associated with aspects of DCM. After review, a refined word list was re-polled for voting and word submission. Word clouds were generated and an implementation plan for AO Spine RECODE-DCM PSP surveys was subsequently developed., Results: Seventy-nine terms were submitted after the first poll. Eighty-seven refined words were then re-polled (which added a further 39 words). Four word clouds were generated under the categories of diagnosis, management, long-term effects, and other. A 1:1 block randomization protocol to assess word cloud impact on the number and relevance of PSP research questions was generated., Conclusions: We have shown it is feasible to work with PwCM to generate a tool for the AO Spine RECODE-DCM nested methodological study. Once the survey stage is completed, we will be able to evaluate the impact of the word clouds. Further research will be needed to assess the value of any impact in terms of stimulating a more creative research agenda.

The beadlet anemone Actinia equina (L.) (Cnidaria: Anthozoa: Actiniaria: Actiniidae) is one of the most familiar organisms of the North European intertidal zone. Once considered a single, morphologically variable species across northern Europe, it is now recognised as one member of a variable species complex. Previous studies of distribution, aggression, allozymes and mitochondrial DNA suggest that the diversity in form and colour within A. equina may hide still unrecognised species diversity. To empower further study of A. equina population genetics and systematics, we sequenced (PacBio Sequel) the genome of a single A. equina individual to produce a high-quality genome assembly (contig N 50  = 492,607 bp, 1485 contigs, number of protein coding genes = 47,671, 97% BUSCO completeness). There is debate as to whether A. equina reproduces solely asexually, since no reliable, consistent evidence of sexual reproduction has been found. To gain further insight, we examined the genome for evidence of a 'meiotic toolkit' - genes believed to be found consistently in sexually reproducing organisms - and demonstrate that the A. equina genome appears not to have this full complement. Additionally, Smudgeplot analysis, coupled with high haplotype diversity, indicates this genome assembly to be of ambiguous ploidy, suggesting that A. equina may not be diploid. The suggested polyploid nature of this species coupled with the deficiency in meiotic toolkit genes, indicates that further field and laboratory studies of this species is warranted to understand how this species reproduces and what role ploidy may play in speciation within this speciose genus., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Social tipping, where minorities trigger larger populations to engage in collective action, has been suggested as one key aspect in addressing contemporary global challenges. Here, we refine Granovetter's widely acknowledged theoretical threshold model of collective behavior as a numerical modelling tool for understanding social tipping processes and resolve issues that so far have hindered such applications. Based on real-world observations and social movement theory, we group the population into certain or potential actors, such that - in contrast to its original formulation - the model predicts non-trivial final shares of acting individuals. Then, we use a network cascade model to explain and analytically derive that previously hypothesized broad threshold distributions emerge if individuals become active via social interaction. Thus, through intuitive parameters and low dimensionality our refined model is adaptable to explain the likelihood of engaging in collective behavior where social-tipping-like processes emerge as saddle-node bifurcations and hysteresis.

An unusual trithioorthoformate-capped cyclophane cage was assembled via antimony-activated iodine oxidation of thiols as confirmed by 1 H-NMR spectroscopy and X-ray crystallography. The disulfide bridges can undergo desulfurization with hexamethylphosphorous triamide (HMPT) at ambient temperature to capture a trithioether cyclophane cage capped by the trithioorthoformate. In both cages a methine proton points directly into the small cavity. This unexpected structure is hypothesized to have formed as a result of haloform insertion during oxidation., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Bone collagen is an important material for radiocarbon, paleodietary, and paleoproteomic analyses, but it degrades over time, making such analyses more difficult with older material. Collagen preservation between and within archaeological sites is also variable, so that much time, effort, and money can go into the preparation and initial analysis of samples that will not yield meaningful results. To avoid this, various methods are employed to prescreen bone for collagen preservation (e.g., %N, microporosity, and FTIR spectroscopic analyses), but these are often destructive and/or require exportation for analysis. Here, we explore near-infrared spectroscopy as a tool for gauging the collagen content of ground and whole bone from about 500 to 45,000 years ago. We show that a portable spectrometer's ability to quantify collagen content and classify specimens by preservation status is comparable to that of other popular prescreening methods. Moreover, near-infrared spectroscopy is non-destructive and spectra can be acquired in a few seconds.

Biochemistry is a core component of medical education as it contributes to the fundamental basis and understanding of molecular mechanisms in pathophysiological processes. The convergence of nutritional factors also gives insight to many chronic diseases. Topics of nutrition are often incorporated into biochemistry coursework and must be integrated in a way that makes sense within the overall curriculum. An important issue raised by this structure is determining which topics are most important to a student's understanding and what topics are most relevant to future clinical practice. Previous surveys show medical undergraduates feel that much of current medical biochemistry coursework lacks clinical relevance and pays too much attention to small details. Here we report the results of a survey that aims to determine the biochemical and nutritional topics that physicians and educators feel are most important to teach in medical school. This information is important for medical schools to better prepare their students for what they will see and apply in their future clinical practice. Physicians and medical educators were surveyed, asked demographic questions, and then requested to provide a prioritized list of the top 10 biochemistry and nutrition topics that they believed should be focused on in undergraduate medical education. Topics suggested by participants were normalized for spelling, acronyms, and abbreviations and given a weight from 10 to 1. A prioritized list was then created based on the suggested topics. This list provides insight into the topics that medical educators and physicians consider important to cover in undergraduate medical education., Competing Interests: Conflict of InterestThe authors declare that they have no competing interests., (© International Association of Medical Science Educators 2018.)

The thermoregulatory responses of owls to heat stress have been the subject of few studies. Although nocturnality buffers desert-dwelling owls from significant heat stress during activity, roost sites in tree and cactus cavities or in deep shade provide only limited refuge from high environmental temperatures during the day. We measured thermoregulatory responses to acute heat stress in two species of small owls, the elf owl ( Micrathene whitneyi ) and the western screech-owl ( Megascops kennicottii ), which occupy the Sonoran Desert of southwestern North America, an area of extreme heat and aridity. We exposed wild-caught birds to progressively increasing air temperatures ( T a ) and measured resting metabolic rate (RMR), evaporative water loss (EWL), body temperature ( T b ) and heat tolerance limits (HTL; the maximum T a reached). Comparatively low RMR values were observed in both species, T b approximated T a at 40°C and mild hyperthermia occurred as T a was increased toward the HTL. Elf owls and screech-owls reached HTLs of 48 and 52°C, respectively, and RMR increased to 1.5 and 1.9 times thermoneutral values. Rates of EWL at the HTL allowed for the dissipation of 167-198% of metabolic heat production (MHP). Gular flutter was used as the primary means of evaporative heat dissipation and produced large increases in evaporative heat loss (44-100%), accompanied by only small increases (<5%) in RMR. These small, cavity-nesting owls have thermoregulatory capacities that are intermediate between those of the open-ground nesting nightjars and the passerines that occupy the same ecosystem., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2018. Published by The Company of Biologists Ltd.)

Avian orders differ in their thermoregulatory capabilities and tolerance of high environmental temperatures. Evaporative heat loss, and the primary avenue whereby it occurs, differs amongst taxa. Although Australian parrots (Psittaciformes) have been impacted by mass mortality events associated with extreme weather events (heat waves), their thermoregulatory physiology has not been well characterized. We quantified the upper limits to thermoregulation under extremely hot conditions in two Australian parrots: the mulga parrot ( Psephotellus varius ; ∼55 g) and the galah ( Eolophus roseicapilla ; ∼265 g). At air temperatures ( T a ) exceeding body temperature ( T b ), both species showed increases in T b to maximum values around 43-44°C, accompanied by rapid increases in resting metabolic rate above clearly defined upper critical limits of thermoneutrality and increases in evaporative water loss to levels equivalent to 700-1000% of baseline rates at thermoneutral T a Maximum cooling capacity, quantified as the fraction of metabolic heat production dissipated evaporatively, ranged from 1.71 to 1.79, consistent with the known range for parrots, similar to the corresponding range in passerines, and well below the corresponding ranges for columbids and caprimulgids. Heat tolerance limit (the maximum T a tolerated) ranged from 44 to 55°C, similar to the range reported for passerines, but lower than that reported for columbids and caprimulgids. Our data suggest that heat tolerance in parrots is similar to that in passerines. We argue that understanding how thermoregulatory capacity and heat tolerance vary across avian orders is vital for predicting how climate change and the associated increase in frequency of extreme weather events may impact avian populations in the future., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2018. Published by The Company of Biologists Ltd.)

Competing Interests: I confirm that we, the authors, have read and understood the BMJ policy on declaration of interests and have no competing interests to declare.

We examined thermoregulatory performance in seven Sonoran Desert passerine bird species varying in body mass from 10 to 70 g - lesser goldfinch, house finch, pyrrhuloxia, cactus wren, northern cardinal, Abert's towhee and curve-billed thrasher. Using flow-through respirometry, we measured daytime resting metabolism, evaporative water loss and body temperature at air temperatures ( T air ) between 30 and 52°C. We found marked increases in resting metabolism above the upper critical temperature ( T uc ), which for six of the seven species fell within a relatively narrow range (36.2-39.7°C), but which was considerably higher in the largest species, the curve-billed thrasher (42.6°C). Resting metabolism and evaporative water loss were minimal below the T uc and increased with T air and body mass to maximum values among species of 0.38-1.62 W and 0.87-4.02 g H 2 O h -1 , respectively. Body temperature reached maximum values ranging from 43.5 to 45.3°C. Evaporative cooling capacity, the ratio of evaporative heat loss to metabolic heat production, reached maximum values ranging from 1.39 to 2.06, consistent with known values for passeriforms and much lower than values in taxa such as columbiforms and caprimulgiforms. These maximum values occurred at heat tolerance limits that did not scale with body mass among species, but were ∼50°C for all species except the pyrrhuloxia and Abert's towhee (48°C). High metabolic costs associated with respiratory evaporation appeared to drive the limited heat tolerance in these desert passeriforms, compared with larger desert columbiforms and galliforms that use metabolically more efficient mechanisms of evaporative heat loss., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2017. Published by The Company of Biologists Ltd.)

Evaporative heat loss pathways vary among avian orders, but the extent to which evaporative cooling capacity and heat tolerance vary within orders remains unclear. We quantified the upper limits to thermoregulation under extremely hot conditions in five Australian passerines: yellow-plumed honeyeater ( Lichenostomus ornatus ; ∼17 g), spiny-cheeked honeyeater ( Acanthagenys rufogularis ; ∼42 g), chestnut-crowned babbler ( Pomatostomus ruficeps ; ∼52 g), grey butcherbird ( Cracticus torquatus ; ∼86 g) and apostlebird ( Struthidea cinerea ; ∼118 g). At air temperatures ( T a ) exceeding body temperature ( T b ), all five species showed increases in T b to maximum values around 44-45°C, accompanied by rapid increases in resting metabolic rate above clearly defined upper critical limits of thermoneutrality and increases in evaporative water loss (EWL) to levels equivalent to 670-860% of baseline rates at thermoneutral T a Maximum cooling capacity, quantified as the fraction of metabolic heat production dissipated evaporatively, ranged from 1.20 to 2.17, consistent with the known range for passerines, and well below the corresponding ranges for columbids and caprimulgids. Heat tolerance limit (HTL, the maximum T a tolerated) scaled positively with body mass, varying from 46°C in yellow-plumed honeyeaters to 52°C in a single apostlebird, but was lower than that of three southern African ploceid passerines investigated previously. We argue this difference is functionally linked to a smaller scope for increases in EWL above baseline levels. Our data reiterate the reliance of passerines in general on respiratory evaporative heat loss via panting, but also reveal substantial within-order variation in heat tolerance and evaporative cooling capacity., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2017. Published by The Company of Biologists Ltd.)

Memory formation requires the temporal coordination of molecular events and cellular processes following a learned event. During Pavlovian threat (fear) conditioning (PTC), sensory and neuromodulatory inputs converge on post-synaptic neurons within the lateral nucleus of the amygdala (LA). By activating an intracellular cascade of signaling molecules, these G-protein-coupled neuromodulatory receptors are capable of recruiting a diverse profile of plasticity-related proteins. Here we report that norepinephrine, through its actions on β-adrenergic receptors (βARs), modulates aversive memory formation following PTC through two molecularly and temporally distinct signaling mechanisms. Specifically, using behavioral pharmacology and biochemistry in adult rats, we determined that βAR activity during, but not after PTC training initiates the activation of two plasticity-related targets: AMPA receptors (AMPARs) for memory acquisition and short-term memory and extracellular regulated kinase (ERK) for consolidating the learned association into a long-term memory. These findings reveal that βAR activity during, but not following PTC sets in motion cascading molecular events for the acquisition (AMPARs) and subsequent consolidation (ERK) of learned associations.

Extreme high environmental temperatures produce a variety of consequences for wildlife, including mass die-offs. Heat waves are increasing in frequency, intensity, and extent, and are projected to increase further under climate change. However, the spatial and temporal dynamics of die-off risk are poorly understood. Here, we examine the effects of heat waves on evaporative water loss (EWL) and survival in five desert passerine birds across the southwestern United States using a combination of physiological data, mechanistically informed models, and hourly geospatial temperature data. We ask how rates of EWL vary with temperature across species; how frequently, over what areas, and how rapidly lethal dehydration occurs; how EWL and die-off risk vary with body mass; and how die-off risk is affected by climate warming. We find that smaller-bodied passerines are subject to higher rates of mass-specific EWL than larger-bodied counterparts and thus encounter potentially lethal conditions much more frequently, over shorter daily intervals, and over larger geographic areas. Warming by 4 °C greatly expands the extent, frequency, and intensity of dehydration risk, and introduces new threats for larger passerine birds, particularly those with limited geographic ranges. Our models reveal that increasing air temperatures and heat wave occurrence will potentially have important impacts on the water balance, daily activity, and geographic distribution of arid-zone birds. Impacts may be exacerbated by chronic effects and interactions with other environmental changes. This work underscores the importance of acute risks of high temperatures, particularly for small-bodied species, and suggests conservation of thermal refugia and water sources.

Birds show phylogenetic variation in the relative importance of respiratory versus cutaneous evaporation, but the consequences for heat tolerance and evaporative cooling capacity remain unclear. We measured evaporative water loss (EWL), resting metabolic rate (RMR) and body temperature (Tb) in four arid-zone columbids from southern Africa [Namaqua dove (Oena capensis, ∼37 g), laughing dove (Spilopelia senegalensis, ∼89 g) and Cape turtle dove (Streptopelia capicola, ∼148 g)] and Australia [crested pigeon (Ocyphaps lophotes), ∼186 g] at air temperatures (Ta) of up to 62°C. There was no clear relationship between body mass and maximum Ta tolerated during acute heat exposure. Maximum Tb at very high Ta was 43.1±1.0, 43.7±0.8, 44.7±0.3 and 44.3±0.8°C in Namaqua doves, laughing doves, Cape turtle doves and crested pigeons, respectively. In all four species, RMR increased significantly at Ta above thermoneutrality, but the increases were relatively modest with RMR at Ta=56°C being 32, 60, 99 and 11% higher, respectively, than at Ta=35°C. At the highest Ta values reached, evaporative heat loss was equivalent to 466, 227, 230 and 275% of metabolic heat production. The maximum ratio of evaporative heat loss to metabolic production observed in Namaqua doves, 4.66, exceeds by a substantial margin previous values reported for birds. Our results support the notion that cutaneous evaporation provides a highly efficient mechanism of heat dissipation and an enhanced ability to tolerate extremely high Ta., (© 2016. Published by The Company of Biologists Ltd.)

Learning Objectives: After participating in this activity, learners should be better able to:• Evaluate the rationale for screening women for postpartum depression• Assess tools for screening for postpartum depression, Objective: To perform a qualitative literature review on screening for postpartum depression (PPD), as applicable to the general psychiatrist. Results are classified by instrument, timing, and clinical setting of the screen., Data Sources: A literature search was conducted using the PubMed database for English-language articles published since January 1987. Of the 2406 citations initially identified, 61 articles remained after application of inclusion and exclusion criteria., Results: Among numerous screening tools for PPD, the Edinburgh Postnatal Depression Scale is the most widely used. Data suggest that screening for PPD should commence soon after delivery, with subsequent screens at multiple time-points in the postpartum period. Primary care, pediatric, and obstetric settings are all viable locations for screening, but are ineffective without follow-up mental health evaluations. Less data are available to define optimal patterns either for screening in psychiatric settings or for the psychiatrist's role in managing perinatal depression., Conclusions: The American Congress of Obstetricians and Gynecologists, American Academy of Pediatrics, and most authors firmly recommend screening for PPD. The Edinburgh Postnatal Depression Scale can be administered in various clinical settings. Screening should occur at multiple time-points throughout the first postpartum year. The psychiatrist's role in early detection and prevention of PPD requires further exploration.

The kisspeptin system plays pivotal roles in the regulation of vertebrate reproduction. Classically, kisspeptin produced in the brain stimulates brain gonadotropin-releasing hormone signaling, which in turn activates the pituitary-gonad axis. Expression of the kisspeptin system has also been documented in peripheral tissues, including gonads of mammals and fishes. However, the fish gonadal kisspeptin system remained uncharacterized. Herein we report identification and characterization of four kisspeptin system mRNAs (kisspeptin 1 (kiss1), kiss2, and G protein-coupled receptor 54-1 (gpr54-1) and gpr54-2) in sablefish, Anoplopoma fimbria. Sablefish predicted protein sequences were highly similar to those of other marine teleosts, but less so to freshwater teleosts. Tissue distribution analyses revealed that all four kisspeptin-system transcripts were expressed in both brain and gonad. However, kiss2 was the predominant transcript in the gonads and the only transcript detected in ovulated eggs. Ontogenetic analysis of kiss2 expression in juvenile sablefish gonads demonstrated that levels were low during sex differentiation but increased with fish size and gonadal development. Dramatic increases in kiss2 mRNA occurred during primary oocyte growth, while levels remained relatively low in testes. In situ hybridization revealed that kiss2 mRNA was localized to cytoplasm of perinucleolus stage oocytes, suggesting it could play a local role in oogenesis or could be synthesized and stored within oocytes as maternal mRNA. This represents the first study to focus on the gonadal kisspeptin system in fishes and provides important tools for further investigation of both the gonadal and brain kisspeptin systems in sablefish., (Published by Elsevier Inc.)

Birds in subtropical deserts face significant thermoregulatory challenges because environmental temperatures regularly exceed avian body temperature. To understand the differing susceptibility of desert birds to increasing temperatures, we examined thermoregulatory performance and estimated heat tolerance limits (HTLs) for three Sonoran Desert nesting bird species - Gambel's quail, mourning doves and white-winged doves. Using flow-through respirometry we measured daytime resting metabolism, evaporative water loss and real-time body temperature at air temperatures (T(air)) from 30°C to 66°C. We found marked increases in resting metabolism at the upper critical temperature (T(uc)), which was significantly lower in the quail (T(air)=41.1°C) than in both dove species (T(air)=45.9-46.5°C). Gambel's quail maintained low resting metabolic rates and low rates of evaporative water loss at their T(uc) (0.71 W and 1.20 g H2O h(-1), respectively), but were more sensitive to increasing air temperature, reaching their HTL at T(air) of 52°C. Mourning doves and white-winged doves maintained low resting metabolic rates (0.66 and 0.94 W), but higher rates of evaporative water loss (1.91 and 2.99 g H2O h(-1)) at their T(uc) and reached their HTL at T(air) of 58-60°C. Mass-specific evaporative water loss in white-winged doves (147 g) and mourning doves (104 g) was 45% and 30% greater, respectively, than the rate observed in Gambel's quail (161 g) at Tair of 48°C. Higher rates of evaporation and higher T(uc) made the doves exceptionally heat tolerant, allowing them to maintain body temperatures at least 14°C below air temperatures as high as 60°C (140°F)., (© 2015. Published by The Company of Biologists Ltd.)

Objective: Development of a model for the prediction of δ(13) Cprotein from δ(13) Ccollagen and Δ(13) Cap-co . Model-generated values could, in turn, serve as "consumer" inputs for multisource mixture modeling of paleodiet., Methods: Linear regression analysis of previously published controlled diet data facilitated the development of a mathematical model for predicting δ(13) Cprotein (and an experimentally generated error term) from isotopic data routinely generated during the analysis of osseous remains (δ(13) Cco and Δ(13) Cap-co )., Results: Regression analysis resulted in a two-term linear model (δ(13) Cprotein (%) = (0.78 × δ(13) Cco ) - (0.58× Δ(13) Cap-co ) - 4.7), possessing a high R-value of 0.93 (r(2)  = 0.86, P < 0.01), and experimentally generated error terms of ±1.9% for any predicted individual value of δ(13) Cprotein . This model was tested using isotopic data from Formative Period individuals from northern Chile's Atacama Desert., Conclusions: The model presented here appears to hold significant potential for the prediction of the carbon isotope signature of dietary protein using only such data as is routinely generated in the course of stable isotope analysis of human osseous remains. These predicted values are ideal for use in multisource mixture modeling of dietary protein source contribution., (© 2015 Wiley Periodicals, Inc.)

Environmental temperatures that exceed body temperature (Tb) force endothermic animals to rely solely on evaporative cooling to dissipate heat. However, evaporative heat dissipation can be drastically reduced by environmental humidity, imposing a thermoregulatory challenge. The goal of this study was to investigate the effects of humidity on the thermoregulation of desert birds and to compare the sensitivity of cutaneous and respiratory evaporation to reduced vapor density gradients. Rates of evaporative water loss, metabolic rate, and Tb were measured in birds exposed to humidities ranging from ∼2 to 30 g H2O m(-3) (0%-100% relative humidity at 30°C) at air temperatures between 44° and 56°C. In sociable weavers, a species that dissipates heat primarily through panting, rates of evaporative water loss were inhibited by as much as 36% by high humidity at 48°C, and these birds showed a high degree of hyperthermia. At lower temperatures (40°-44°C), evaporative water loss was largely unaffected by humidity in this species. In Namaqua doves, which primarily use cutaneous evaporation, increasing humidity reduced rates of evaporative water loss, but overall rates of water loss were lower than those observed in sociable weavers. Our data suggest that cutaneous evaporation is more efficient than panting, requiring less water to maintain Tb at a given temperature, but panting appears less sensitive to humidity over the air temperature range investigated here.

A group training format was compared to one-to-one training in a cognitive intervention, Reasoning Exercises in Assisted Living (REAL), designed for elderly Assisted Living residents. Change scores on problem solving and functional outcomes were compared between participants in each group. In participants trained individually (n = 29), scores increased post-intervention on the Every Day Problems Test for Cognitively Challenged Elders (EPCCE; d = 3.10, p < 0.01) and the Direct Assessment of Functional Status (DAFS; d = 3.52, p < 0.001), at a cost of $132 per person. Participants (N = 4) in the group format REAL had mean score increases of 2.75 points on the EPCCE and 3.5 on the DAFS, at a cost of $25.60 per person. Additional testing is warranted to verify the group effects due to the limited size of the sample. Relative costs and effects of various training formats are important to consider when developing, testing, and disseminating interventions targeting older adults., (Copyright © 2014 Mosby, Inc. All rights reserved.)

Regardless of how sex is determined, the gonadal genes expressed downstream that regulate sex differentiation are relatively conserved among vertebrates. The goal of this study was to clone and characterize five key sex differentiation-related genes in a Scorpaeniform fish, sablefish (Anoplopoma fimbria). Complete mRNA sequences of foxl2, cyp19a1a, dmrt1, sox9a and amh were cloned, sequenced, and phylogenetically analyzed. The sablefish mRNA sequences exhibited the characteristic domains of each gene. The deduced amino sequences were highly conserved in some cases, such as Foxl2, whereas others, such as Amh, exhibited lower homology to corresponding sequences in other vertebrates. Using quantitative PCRs developed for each gene, we found that foxl2 and cyp19a1a mRNA levels were significantly elevated in juvenile sablefish ovaries compared to testes, whereas dmrt1, sox9a and amh mRNA levels were significantly elevated in testes relative to ovaries. These patterns were upheld in our tissue distribution analyses of adult fish, but overall four of the genes, foxl2, cyp19a1a, dmrt1 and amh, were robust markers of sex in sablefish. This study provides important molecular tools for ongoing work related to sex control in sablefish and exploration of the earliest period of molecular sex differentiation and its regulation., (Published by Elsevier Inc.)

Background: This review summarizes peer-reviewed studies examining cancer risks among police officers. It provides an overview of existing research limitations and uncertainties and the plausible etiologic risk factors associated with cancer in this understudied occupation., Methods: Previous cancer studies among police officers were obtained via a systematic review of the MEDLINE, CABDirect, and Web of Science bibliographic databases., Results: Quality observational studies of cancer among police officers are sparse and subject to limitations in exposure assessment and other methods. Results from three studies suggested possible increased mortality risks for all cancers, and cancers of the colon, kidney, digestive system, esophagus, male breast, and testis, as well as Hodgkin's disease. Few incidence studies have been performed, and results have been mixed, although some associations with police work have been observed for thyroid, skin, and male breast cancer., Conclusions: Police are exposed to a mix of known or suspected agents or activities that increase cancer risk. Epidemiologic evidence to date is sparse and inconsistent. There is a critical need for more research to understand the biological and social processes underlying exposures and the suggested disproportionate risks and to identify effective prevention strategies., (Copyright © 2012 Wiley Periodicals, Inc.)

Background: Near infrared spectroscopy (NIRS) has been suggested as a possible means for detecting perfusion deficits in patients with acute compartment syndrome (ACS)., Study Objectives: To longitudinally examine NIRS in an ACS model to determine its responsiveness to decreasing perfusion pressure., Methods: A NIRS sensor pad was placed under a tourniquet over the anterior compartment in the mid-tibia region on 20 volunteers. Initial perfusion pressures and NIRS values were recorded. The tourniquet pressure was sequentially raised by 10 mm Hg in 10-min intervals until systolic pressure was surpassed. NIRS values and perfusion pressure were determined at the end of each 10-min interval., Results: There was no change in mean NIRS values from the initial baseline until 30 mm Hg of perfusion pressure was reached. Additionally, a statistically significant drop in mean NIRS values was observed as perfusion pressures dropped from 10 mm Hg to 0 mm Hg, and again with subsequent decreases of 10 mm Hg perfusion pressure until systolic pressure was surpassed., Conclusions: These results coincide with previously published studies using alternative methods of measuring blood flow or perfusion. NIRS values were responsive to decreasing perfusion pressures over a longitudinal period of time in an ACS model. These results suggest that NIRS may be useful for continuous, non-invasive monitoring of patients for whom ACS is a concern. Additional studies on traumatized patients are required., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Holoprosencephaly (HPE), the most common malformation of the human forebrain, may result from mutations in over 12 genes. Sonic Hedgehog (SHH) was the first such gene discovered; mutations in SHH remain the most common cause of non-chromosomal HPE. The severity spectrum is wide, ranging from incompatibility with extrauterine life to isolated midline facial differences., Objective: To characterise genetic and clinical findings in individuals with SHH mutations., Methods: Through the National Institutes of Health and collaborating centres, DNA from approximately 2000 individuals with HPE spectrum disorders were analysed for SHH variations. Clinical details were examined and combined with published cases., Results: This study describes 396 individuals, representing 157 unrelated kindreds, with SHH mutations; 141 (36%) have not been previously reported. SHH mutations more commonly resulted in non-HPE (64%) than frank HPE (36%), and non-HPE was significantly more common in patients with SHH than in those with mutations in the other common HPE related genes (p<0.0001 compared to ZIC2 or SIX3). Individuals with truncating mutations were significantly more likely to have frank HPE than those with non-truncating mutations (49% vs 35%, respectively; p=0.012). While mutations were significantly more common in the N-terminus than in the C-terminus (including accounting for the relative size of the coding regions, p=0.00010), no specific genotype-phenotype correlations could be established regarding mutation location., Conclusions: SHH mutations overall result in milder disease than mutations in other common HPE related genes. HPE is more frequent in individuals with truncating mutations, but clinical predictions at the individual level remain elusive.

Aims: Peer substance involvement (PSI) is a robust correlate of adolescent substance use. A small number of genetically informative studies suggest that shared genetic and environmental factors contribute to this association. We examine mechanisms by which PSI influences the etiology of regular substance involvement (RSI), particularly in women., Design: Population-based cohort study of twin women from the US Midwest., Participants: 2176 twin women., Measurements: To examine the relationship between self-reported PSI during adolescence and a composite RSI representing regular tobacco, alcohol and cannabis use during young adulthood, using genetically informative correlation, moderation and joint correlation-moderation models., Findings: There was evidence for a significant additive genetic X environment interaction. PSI was moderately heritable (h(2) = 0.25). Genetic, shared and non-shared influences on RSI overlapped with influences on PSI (genetic correlation of 0.43). Even after controlling for these shared genetic influences, RSI was more heritable in those reporting greater PSI., Conclusions: While young women may select peers based on certain dispositional traits (e.g. permissiveness towards substance use), the social milieu constructed by PSI does modify the architecture of increased RSI in those individuals with increasing levels of PSI being associated with stronger expression of heritable influences., (© 2010 The Authors, Addiction © 2010 Society for the Study of Addiction.)

Purpose: While disclosing a cancer diagnosis to a patient is common practice, how it is disclosed and the impact it has on the patient are poorly understood. We examined how cancer diagnoses were first given to patients and the impact of different aspects of disclosure on patient satisfaction., Patients and Methods: We provided a self-administered questionnaire to a total of 460 oncology patients of the National Cancer Institute (NCI) being treated at the National Institutes of Health (NIH) Clinical Center in Bethesda, MD., Results: Of the 437 patients who completed the survey, 54% were told their diagnosis in-person in the physician's office, 18% by phone, and 28% in the hospital. Forty-four percent of patients reported discussions of 10 minutes or fewer, 53% reported discussions lasting longer than 10 minutes, and 5% could not remember. Treatment options were not discussed for 31% of those who could clearly remember. Higher mean satisfaction scores were associated with diagnoses revealed in person rather than over the phone (68.2 +/- 1.6 v 47.2 +/- 3.7), diagnoses revealed in a personal setting rather than an impersonal setting (68.9 +/- 1.6 v 55.7 +/- 2.8), discussions lasting longer than 10 minutes rather than fewer than 10 minutes (73.5 +/- 1.9 v 54.1 +/- 2.4), and inclusion of treatment options rather than exclusion (72.0 +/- 1.9 v 50.7 +/- 3.2; P < .001 for each aspect)., Conclusion: Physicians should disclose a cancer diagnosis in a personal setting, discussing the diagnosis and treatment options for a substantial period of time whenever possible.

We report a case of acute chylous peritonitis mimicking acute appendicitis in a man with acute on chronic pancreatitis. Pancreatitis, both acute and chronic, causing the development of acute chylous ascites and peritonitis has rarely been reported in the English literature. This is the fourth published case of acute chylous ascites mimicking acute appendicitis in the literature.

Aim: To compare the muscular load (level of muscle activity) to the shoulder during alternative approaches to trigger point therapy (TPT)., Method: Massage therapy students (n=7) applied a predetermined level of force to an artificial contact surface. Changes in five pairs of superficial shoulder muscles (indicated by surface electromyography) were recorded while the student performed the single-arm technique (SAT), the double-arm technique (DAT) and the treatment-tool technique (TTT) using TriggerMate, a new treatment tool., Results: For the contact arm, muscle activity was significantly decreased using the TTT compared to the SAT (p<0.05) but was not significantly different between the TTT and DAT. For the non-contact arm, none of the test techniques led to significant differences in muscle activity., Conclusions: While there is evidence that the TTT decreases the muscular load to the shoulder of the contact arm, there is no indication of where this load is redistributed.

Understanding the role that molecular compounds have in cancer is of significant interest, as the identification of molecular markers will aid in the prevention and elimination of cancer. Completing this expansive puzzle proves to be challenging because there is great diversity among tumors, specifically within the microenvironment. In a recent article by Chang et al. published in The Journal of the National Cancer Institute (Vol., 2006) new insight is provided of three specific molecular compounds: hypoxia-inducible factor-1alpha (HIF-1alpha), the connective tissue growth factor (CTGF) and the vascular endothelial growth factor-A (VEGF-A). As shown by Chang et al., these molecular compounds have significant implications in the role of human lung adenocarcinoma, and are shown to be integral within this microenvironment. This journal club article reviews the study of Chang et al. and briefly discusses the broader implications of their findings.

Immunoassays are commonly used to screen samples prior to confirmation by gas chromatography-mass spectrometry (GC-MS). This serves two purposes: it provides a second method for positive samples, and it allows exclusion of negative samples from further confirmatory testing. In addition, immunoassay results can be used in some cases to determine if dilution of the sample will be required during the confirmatory assay. We used 878 sweat patches worn by 38 subjects receiving treatment for cocaine dependence to compare analysis of the extracts of the patches for cocaine immuno-equivalents by radioimmunoassay (RIA) with determination of cocaine, benzoylecgonine (BE), and ecgonine methyl ester (EME) by GC-MS. Preliminary validation experiments demonstrate that the GC-MS method using positive ion chemical ionization had sufficient specificity and recovery to support a lower limit of quantitation (LLOQ) of 4 ng/patch and was precise and accurate across a linear range up to 500 ng/patch. Cocaine ranging from the LLOQ to 31,900 ng/patch was found in 660 of the samples; BE ranging from the LLOQ to 3470 ng/patch was found in 530 of the samples; and EME ranging from the LLOQ to 2280 ng/patch was found in 476 of the samples. In a subset of 238 samples semiquantitative use of the RIA gave results that agreed with GC-MS with a correlation coefficient of 0.986, but averaged approximately 23% lower. Although this accuracy of the RIA supported its use as a sole quantitative assay, the limited linear range of the RIA (4-200 ng/patch) proved impractical for this purpose. Receiver operator characteristic analysis of the cutoffs of the RIA and GC-MS suggested optimal cutoffs of 5 and 4 ng/patch, respectively. At these cutoffs, the RIA had sensitivity of 90.0% and specificity of 92.2%. For samples that had RIA results greater than the high calibrator (N = 228), various dilution schemes were assessed for their ability to predict retention of either cocaine alone or cocaine and both metabolites within the linear range of the GC-MS. When cocaine was the only analyte of interest, a single 20-fold dilution retained 200 (87.7%) of the samples. This compared to an optimal scheme where a different dilution was selected for each one-tenth ratio (< 0.1, 0.1-0.2, etc.) where 211 (92.5%) of the samples were retained. When trying to retain cocaine and both metabolites, dilution schemes were less successful as BE and EME would often fall below the LLOQ of the GC-MS. A single fivefold dilution of all samples retained 115 (50.4%) compared to an optimum of 143 (62.7%). The optimum could be approached with four dilution sets retaining 142 of the samples. Time expended on performing RIA analysis of all the samples was cost-effective when the results were used to exclude negatives from and predict dilutions required for GC-MS analysis. RIA offers a cost-effective, sensitive, and specific alternative initial test for cocaine determination in extracts of sweat patches.

Delta9-tetrahydrocannabinol (THC) and 11-nor-9-carboxy-delta9-tetrahydrocannabinol (THCA) in human plasma can be simultaneously detected using solid-phase extraction with gas chromatography and negative ion chemical ionization mass spectrometry. THC-d3 and THCA-d3 are added as internal standards; protein is precipitated with acetonitrile and the resulting supernatants diluted with 0.1 M sodium acetate (pH 7.0) prior to application to the solid-phase extraction columns. THC and THCA were eluted separately and then pooled, dried under air, and derivatized with trifluoroacetic anhydride and hexafluoroisopropanol. The derivatized THC-d0 gives abundant molecular anions (m/z 410), and the derivatized THCA-d0 gives abundant fragment ions (m/z 422) formed by loss of (CF3)2CHOH from its molecular anion. The recoveries of THC and THCA were 74% and 17%, respectively. The lower and upper limits of quantitation were 0.5 and 100 ng/mL for THC and 2.5 ng/mL and 100 ng/mL for THCA. The within-run accuracy and precision for THC (measured at 0.5, 1, 10 and 75 ng/mL) ranged from 98 to 106% (% target) and 4.1 to 9.5 (%CV), respectively. For THCA, the within-run accuracy and precision (measured at 2.5, 5, 10, and 75 ng/mL) ranged from 89 to 101% and 4.3 to 7.5%, respectively. The between-run accuracy and precision for THC ranged from 92 to 110% and 0.4 to 12.4%, respectively. The between-run accuracy and precision for THCA ranged from 97 to 103% and 6.5 to 12.3%, respectively. In processed samples stored in reconstituted form at -20 degrees C, THC and THCA were stable for at least three days. THC and THCA stored in plasma were stable following three freeze/thaw cycles. THC and THCA in whole blood at room temperature for 6 h, or in plasma stored at room temperature for 24 h, did not show significant change. Storage in polypropylene containers for 7 days at -20 degrees C and the presence of 1% sodium fluoride or the cannabinoid receptor antagonist, SR141716, at 1 microg/mL did not interfere with the quantitation of THC and THCA. In three individuals who smoked marijuana under controlled dosing conditions, peak THC concentrations of 151, 266, and 99 ng/mL were seen in the first plasma samples drawn immediately after the end of smoking, and corresponding peak THCA concentrations of 41, 52, and 17 ng/mL occurred at 0.33 to 1 h after cessation of smoking.

Atropine may precipitate angle closure glaucoma in those predisposed to the disorder. Previously reported cases demonstrate the frequent misdiagnosis of acute glaucoma as conjunctivitis. Resultant delays in treatment can lead to vision loss. The present case describes a 66-yr-old man who developed acute angle closure glaucoma after receiving atropine during a coronary angioplasty produce. Clinicians who utilize atropine should be aware of the possibility of precipitating angle closure glaucoma and the predisposing factors, signs, and symptoms to facilitate prompt diagnosis and treatment of this disorder.

A study was conducted of the status of the middle ear in neurologically impaired patients requiring extended nasogastric tube (NGT) feeding. Ninety percent of the study patients with NGTs demonstrated abnormal middle ear function via immittance testing; whereas, 8.5% and 0% of the clinical and normal control samples, respectively, had abnormal findings. These results support the need to conscientiously observe the middle ear status of patients requiring long-term NGT feedings. A plan for monitoring middle ear function in these patients is suggested.