Reductive carboxylation supports growth in tumour cells with defective mitochondria.
Mitochondrial metabolism provides precursors to build macromolecules in growing cancer cells. In normally functioning tumour cell mitochondria, oxidative metabolism of glucose- and glutamine-derived carbon produces citrate and acetyl-coenzyme A for lipid synthesis, which is required for tumorigenesis. Yet some tumours harbour mutations in the citric acid cycle (CAC) or electron transport chain (ETC) that disable normal oxidative mitochondrial function, and it is unknown how cells from such tumours generate precursors for macromolecular synthesis. Here we show that tumour cells with defective mitochondria use glutamine-dependent reductive carboxylation rather than oxidative metabolism as the major pathway of citrate formation. This pathway uses mitochondrial and cytosolic isoforms of NADP(+)/NADPH-dependent isocitrate dehydrogenase, and subsequent metabolism of glutamine-derived citrate provides both the acetyl-coenzyme A for lipid synthesis and the four-carbon intermediates needed to produce the remaining CAC metabolites and related macromolecular precursors. This reductive, glutamine-dependent pathway is the dominant mode of metabolism in rapidly growing malignant cells containing mutations in complex I or complex III of the ETC, in patient-derived renal carcinoma cells with mutations in fumarate hydratase, and in cells with normal mitochondria subjected to acute pharmacological ETC inhibition. Our findings reveal the novel induction of a versatile glutamine-dependent pathway that reverses many of the reactions of the canonical CAC, supports tumour cell growth, and explains how cells generate pools of CAC intermediates in the face of impaired mitochondrial metabolism.


Increased plasma neurofilament light chain levels in patients with type-1 diabetes with impaired awareness of hypoglycemia.
Impaired awareness of hypoglycemia (IAH) is a common complication in patients with type-1 diabetes (T1D). IAH is a major risk factor for severe hypoglycemic events, leading to adverse clinical consequences and cerebral damage. Non-invasive, cost-effective, and logistically efficient biomarkers for this condition have not been validated. Here, we propose plasma neurofilament light chain (NfL) levels as a biomarker of neuroaxonal damage in patients with T1D-IAH. 54 patients were included into the study (18 T1D-IAH, 18 T1D with normal awareness of hypoglycemia (NAH) and 18 healthy controls). We measured plasma NfL levels and studied cerebral gray matter alterations on MRI. We found that NfL levels were increased in patients with T1D-IAH compared with patients with T1D-NAH and healthy controls. Importantly, increased NfL levels correlated with reduced cerebral gray matter volume and increased IAH severity in patients with T1D-IAH. Overall, our findings identify plasma NfL levels as a potential biomarker of cerebral damage in this population, motivating further confirmatory studies with potential implications in clinical trials.


Energyscapes and prey fields shape a North Atlantic seabird wintering hotspot under climate change.
There is an urgent need for a better understanding of animal migratory ecology under the influence of climate change. Most current analyses require long-term monitoring of populations on the move, and shorter-term approaches are needed. Here, we analysed the ecological drivers of seabird migration within the framework of the energyscape concept, which we defined as the variations in the energy requirements of an organism across geographical space as a function of environmental conditions. We compared the winter location of seabirds with their modelled energy requirements and prey fields throughout the North Atlantic. Across six winters, we tracked the migration of 94 little auks (Alle alle), a key sentinel Arctic species, between their East Greenland breeding site and wintering areas off Newfoundland. Winter energyscapes were modelled with Niche Mapper™, a mechanistic tool which takes into account local climate and bird ecophysiology. Subsequently, we used a resource selection function to explain seabird distributions through modelled energyscapes and winter surface distribution of one of their main prey, Calanus finmarchicus. Finally, future energyscapes were calculated according to IPCC climate change scenarios. We found that little auks targeted areas with high prey densities and moderately elevated energyscapes. Predicted energyscapes for 2050 and 2095 showed a decrease in winter energy requirements under the high emission scenario, which may be beneficial if prey availability is maintained. Overall, our study demonstrates the great potential of the energyscape concept for the study of animal spatial ecology, in particular in the context of global change.


Bead-Based Peptide Arrays for Profiling the Specificity of Modification State-Specific Antibodies.
Modification state-specific antibodies are powerful tools for investigating posttranslational modifications in proteins. The majority of these antibodies have been generated against peptide-antigen conjugates. They are useful in a plethora of methods, such as Western blotting, immunohistochemistry, sandwich immunoassay, immunoprecipitation, and immunoprecipitation coupled with mass spectrometry. Phosphorylation, acetylation, methylation, sulfation, nitrosylation, ubiquitination, and sumoylation are some of the modifications that can be studied using such antibodies. However, investigating the on- and off-target binding of antibodies is crucial to the interpretation of experimental data. Peptide arrays are excellent tools for such in-depth studies of off-target and on-target binding of antibodies. Dozens or even hundreds of modified peptides can be integrated into a single experimental setup to analyze the antibody's binding behavior. Here, we propose three different protocols for peptide bead array generation and describe their suitability for such types of assay.


The Bionic Bra: Using electromaterials to sense and modify breast support to enhance active living.
Although the most supportive sports bras can control breast motion and associated breast pain, they are frequently deemed uncomfortable to wear and, as a result, many women report exercise bra discomfort. Given that exercise bra discomfort is associated with decreased levels of physical activity, there is a pertinent need to develop innovative solutions to address this problem. This research aimed to evaluate the use of electromaterial sensors and artificial muscle technology to create a bra that was capable of detecting increases in breast motion and then responding with increased breast support to enhance active living. The research involved two phases: (i) evaluating sensors suitable for monitoring and providing feedback on changes in the amplitude and frequency of breast motion, and (ii) evaluating an actuator capable of changing breast support provided by a bra during activity. When assessed in isolation, the developed technologies were capable of sensing breast motion and actuating to provide some additional breast support. The challenge now lies in integrating both technologies into a functional sports bra prototype, and assessing this prototype in a controlled biomechanical analysis to provide a breast support solution that will enable women to enjoy active living in comfort.


A novel Rab9 effector required for endosome-to-TGN transport.
Rab9 GTPase is required for the transport of mannose 6-phosphate receptors from endosomes to the trans-Golgi network in living cells, and in an in vitro system that reconstitutes this process. We have used the yeast two-hybrid system to identify proteins that interact preferentially with the active form of Rab9. We report here the discovery of a 40-kD protein (p40) that binds Rab9-GTP with roughly fourfold preference to Rab9-GDP. p40 does not interact with Rab7 or K-Ras; it also fails to bind Rab9 when it is bound to GDI. The protein is found in cytosol, yet a significant fraction (approximately 30%) is associated with cellular membranes. Upon sucrose density gradient flotation, membrane- associated p40 cofractionates with endosomes containing mannose 6-phosphate receptors and the Rab9 GTPase. p40 is a very potent transport factor in that the pure, recombinant protein can stimulate, significantly, an in vitro transport assay that measures transport of mannose 6-phosphate receptors from endosomes to the trans-Golgi network. The functional importance of p40 is confirmed by the finding that anti-p40 antibodies inhibit in vitro transport. Finally, p40 shows synergy with Rab9 in terms of its ability to stimulate mannose 6-phosphate receptor transport. These data are consistent with a model in which p40 and Rab9 act together to drive the process of transport vesicle docking.


Neurogenic pulmonary edema in patients with subarachnoid hemorrhage.
Neurogenic pulmonary edema (NPE), leading to cardiopulmonary dysfunction, is a potentially life-threatening complication in patients with aneurysmal subarachnoid hemorrhage (SAH). We sought to assess the clinical presentation and risk factors for the development of NPE after SAH. The database contained prospectively collected information on 477 patients with SAH. Baseline characteristics, clinical and radiologic severity of the bleeding, localization of the ruptured aneurysm, and clinical outcome of patients with NPE were compared with those of patients without NPE. Further, in patients with NPE, intracranial pressure, serum cardiac biomarkers, and hemodynamic parameters during the acute phase were evaluated retrospectively. The incidence of NPE was 8% (39 of 477 patients). Most patients with NPE were severely impaired and all of them presented with radiologically severe hemorrhage. The incidence of NPE was significantly higher in patients with ruptured aneurysm in the posterior circulation. Elevated intracranial pressure was found in 67%, pathologically high cardiac biomarkers in up to 83% of patients with NPE. However, no patient suffered from persistent cardiac dysfunction. Compared with patients without NPE, patients with NPE showed poor neurologic outcome (Glasgow outcome scale 1 to 3 in 25% vs.77% of patients). In conclusion, patients with NPE have a high mortality rate more likely due to their severity grade of the bleeding. Morbidity and mortality due to cardiopulmonary failure might be reduced by appropriate recognition and treatment. The awareness of and knowledge about occurrence, clinical presentation, and treatment of NPE, are essential for all those potentially confronted with patients with SAH in the acute phase.


Multidetector computed tomographic angiography findings in a rare case of popliteal artery entrapment syndrome.
Popliteal artery entrapment syndrome (PAES) is a disorder of the young age group characterized by ischemia of the lower extremities due to an abnormal association between the popliteal artery and adjacent musculotendinous structures. Several underlying anatomical abnormalities causing this syndrome are described and classified. In this study, we present an unusual case of PAES along with multidetector computed tomographic angiography findings.


A genome-wide association study of susceptibility to acute lymphoblastic leukemia in adolescents and young adults.
Acute lymphoblastic leukemia (ALL) in adolescents and young adults (AYA) is characterized by distinct presenting features and inferior prognosis compared with pediatric ALL. We performed a genome-wide association study (GWAS) to comprehensively identify inherited genetic variants associated with susceptibility to AYA ALL. In the discovery GWAS, we compared genotype frequency at 635 297 single nucleotide polymorphisms (SNPs) in 308 AYA ALL cases and 6,661 non-ALL controls by using a logistic regression model with genetic ancestry as a covariate. SNPs that reached P ≤ 5 × 10(-8) in GWAS were tested in an independent cohort of 162 AYA ALL cases and 5,755 non-ALL controls. We identified a single genome-wide significant susceptibility locus in GATA3: rs3824662, odds ratio (OR), 1.77 (P = 2.8 × 10(-10)) and rs3781093, OR, 1.73 (P = 3.2 × 10(-9)). These findings were validated in the replication cohort. The risk allele at rs3824662 was most frequent in Philadelphia chromosome (Ph)-like ALL but also conferred susceptibility to non-Ph-like ALL in AYAs. In 1,827 non-selected ALL cases, the risk allele frequency at this SNP was positively correlated with age at diagnosis (P = 6.29 × 10(-11)). Our results from this first GWAS of AYA ALL susceptibility point to unique biology underlying leukemogenesis and potentially distinct disease etiology by age group.


The impact of alcohol and energy drink consumption on intoxication and risk-taking behavior.
It has been argued that consuming alcohol mixed with energy drinks (AmED) causes a subjective underestimation of intoxication and an increased level of risk-taking behavior. To date, however, there is mixed support for AmED-induced reductions in perceived intoxication, and no objective assessment of risk-taking following AmED consumption. Consequently, the present study aimed to determine the effect of alcohol and energy drink (ED) consumption on subjective measures of intoxication and objective measures of risk-taking. Using a placebo-controlled, single-blind, cross-over design, participants (n = 28) attended 4 sessions in which they were administered, in counterbalanced order: 0.5 g/kg alcohol, 3.57 ml/kg ED, AmED, and a placebo beverage. Participants completed the Biphasic Alcohol Effects Scale and a Subjective Effects Scale at baseline and 30 and 125 minutes postbeverage administration; risk-taking was measured using the Balloon Analogue Risk Task (BART). Participants reported greater subjective intoxication, impairment, and sedation after active relative to placebo alcohol consumption, with no interactive AmED effects. However, a significant moderate magnitude increase in stimulation ratings was observed in the AmED relative to alcohol, ED, and placebo conditions. There was no independent effect of alcohol, or interactive effect with ED, on the BART. A significant, yet small magnitude, increase in risk-taking was evident in active relative to placebo ED conditions. The interactive effect of AmED appears restricted to perceived stimulation, with alcohol-induced increases in subjective intoxication occurring regardless of presence or absence of ED. Engagement in risk-taking behavior was only increased by ED consumption; however, this effect was only of small magnitude; at these doses, alcohol consumption, with or without EDs, did not affect risk-taking. Further research assessing the dose-dependent effects of AmED on objectively measured risk-taking behavior could clarify whether the ED effect increases with higher doses and whether an interactive effect is observed with higher alcohol doses.


Proteolytic processing of an HIV-1 pol polyprotein precursor: insights into the mechanism of reverse transcriptase p66/p51 heterodimer formation.
HIV-1 reverse transcriptase (RT) is a heterodimer comprising a 66 kDa subunit (p66) and a p66-derived 51 kDa subunit (p51). RT is translated as part of a larger gag-pol polyprotein and subsequently processed to the p66/p51 heterodimer by HIV-1 protease (PR) during viral maturation. The processing events involved in the formation of the RT p66 and p51 subunits and the pathway(s) of RT dimer formation are poorly characterized. Attempts to study the kinetics of PR-catalyzed formation of p66/p51 HIV-1 RT in isolated HIV virions produced in the presence of HIV PR inhibitors were unsuccessful due to difficulties in removal of the tight-binding inhibitor to initiate proteolytic processing. Accordingly, an inducible bacterial expression vector encoding a 90 kDa pol polyprotein fragment was constructed. Following expression in Escherichia coli, the pol polyprotein underwent time-dependent proteolytic processing to the RT p66/p51 heterodimer. This processing was catalyzed entirely by HIV-1 PR since mutations that inactivate PR prevented RT heterodimer formation. The kinetics of RT processing follow an ordered sequential pathway in which RT p66 is first excised from the pol polyprotein, followed by formation of the p51 subunit. Processing of the p66 subunit to form p51 apparently proceeds through a p66/p66 RT homodimer intermediate since the L234A mutation in RT, a mutation that prevents RT dimerization, resulted in the formation of RT p66 only. These results provide the first experimental data defining the pathway for the HIV-1 PR catalyzed formation of the p66/p51 HIV-1 RT heterodimer.


Removal of dental amalgam and other metal alloys supported by antioxidant therapy alleviates symptoms and improves quality of life in patients with amalgam-associated ill health.
The purpose of this study was to evaluate treatment of patients suffering from chronic ill health with a multitude of symptoms associated with metal exposure from dental amalgam and other metal alloys. We included 796 patients in a retrospective study using a questionnaire about symptom changes, changes in quality of life as a consequence of treatment and assessment of care taking. Treatment of the patients by removal of offending dental metals and concomitant antioxidant therapy was implemented according to the Uppsala model based on a close co-operation between physicians and dentists. More than 70% of the responders, remaining after exclusion of those who had not begun or completed removal, reported substantial recovery and increased quality of life. Comparison with similar studies showed accordance of the main results. Plasma concentrations of mercury before and after treatment supported the metal exposure to be causative for the ill health. Treatment according to the Uppsala model proved to be adequate for more than 70% of the patients. Patients with a high probability to respond successfully to current therapy might be detected by symptom profiles before treatment. The hypothesis that metal exposure from dental amalgam can cause ill health in a susceptible part of the exposed population was supported. Further research is warranted to develop laboratory tests to support identification of the group of patients responding to current therapy as well as to find out causes of problems in the group with no or negative results.


Vestigial-dependent induction contributes to robust patterning but is not essential for wing-fate recruitment in Drosophila.
Cell recruitment is a process by which a differentiated cell induces neighboring cells to adopt its same cell fate. In Drosophila, cells expressing the protein encoded by the wing selector gene, vestigial (vg), drive a feed-forward recruitment signal that expands the Vg pattern as a wave front. However, previous studies on Vg pattern formation do not reveal these dynamics. Here, we use live imaging to show that multiple cells at the periphery of the wing disc simultaneously activate a fluorescent reporter of the recruitment signal, suggesting that cells may be recruited without the need for their contact neighbors be recruited in advance. In support of this observation, when Vg expression is inhibited either at the dorsal-ventral boundary or away from it, the activation of the recruitment signal still occurs at a distance, suggesting that Vg expression is not absolutely required to send or propagate the recruitment signal. However, the strength and extent of the recruitment signal is clearly compromised. We conclude that a feed-forward, contact-dependent cell recruitment process is not essential for Vg patterning, but it is necessary for robustness. Overall, our findings reveal a previously unidentified role of cell recruitment as a robustness-conferring cell differentiation mechanism.


Infant gut immunity: a preliminary study of IgA associations with breastfeeding.
Secretory immunoglobulin A (IgA) plays a critical role in gut mucosal immune defense. Initially provided by breastmilk, IgA production by the infant gut is gradually stimulated by developing gut microbiota. This study reports associations between infant fecal IgA concentrations 4 months after birth, breastfeeding status and other pre/postnatal exposures in 47 infants in the Canadian Healthy Infant Longitudinal Development cohort. Breastfed infants and first-born infants had higher median fecal IgA concentrations (23.11 v. 9.34 µg/g protein, P<0.01 and 22.19 v. 8.23 µg/g protein, P=0.04). IgA levels increased successively with exclusivity of breastfeeding (β-coefficient, 0.37, P<0.05). This statistical association was independent of maternal parity and household pets. In the absence of breastfeeding, female sex and pet exposure elevated fecal IgA to levels found in breastfed infants. In addition to breastfeeding, infant fecal IgA associations with pre/postnatal exposures may affect gut immunity and risk of allergic disease.


Connectivity and Dispersal Patterns of Protected Biogenic Reefs: Implications for the Conservation of Modiolus modiolus (L.) in the Irish Sea.
Biogenic reefs created by Modiolus modiolus (Linnaeus, 1758) (horse mussel reefs) are marine habitats which support high levels of species biodiversity and provide valuable ecosystem services. Currently, M. modiolus reefs are listed as a threatened and/or declining species and habitat in all OSPAR regions and thus are highlighted as a conservation priority under the EU Marine Strategy Framework Directive (MSFD). Determining patterns of larval dispersal and genetic connectivity of remaining horse mussel populations can inform management efforts and is a critical component of effective marine spatial planning (MSP). Larval dispersal patterns and genetic structure were determined for several M. modiolus bed populations in the Irish Sea including those in Wales (North Pen Llŷn), Isle of Man (Point of Ayre) and Northern Ireland (Ards Peninsula and Strangford Lough). Simulations of larval dispersal suggested extant connectivity between populations within the Irish Sea. Results from the genetic analysis carried out using newly developed microsatellite DNA markers were consistent with those of the biophysical model. Results indicated moderately significant differentiation between the Northern Ireland populations and those in the Isle of Man and Wales. Simulations of larval dispersal over a 30 day pelagic larval duration (PLD) suggest that connectivity over a spatial scale of 150km is possible between some source and sink populations. However, it appears unlikely that larvae from Northern Ireland will connect directly with sites on the Llŷn or Isle of Man. It also appears unlikely that larvae from the Llŷn connect directly to any of the other sites. Taken together the data establishes a baseline for underpinning management and conservation of these important and threatened marine habitats in the southern part of the known range.


The role of endoplasmic reticulum in cadmium-induced mesangial cell apoptosis.
Cd is an industrial and environmental pollutant that affects many organs in humans and other mammals. However, the molecular mechanisms of Cd-induced nephrotoxicity are unclear. In this study, we show that endoplasmic reticula (ER) played a pivotal role in Cd-induced apoptosis in mesangial cells. Using Fluo-3 AM, the intracellular concentration of calcium ([Ca(2+)](i)) was detected as being elevated as time elapsed after Cd treatment. Co-treatment with BAPTA-AM, a calcium chelator, was able to significantly suppress Cd-induced apoptosis. Calcineurin is a cytosolic phosphatase, which was able to dephosphorylate the inositol-1,4,5-triphosphate receptor (IP(3)R) calcium channel to prevent the release of calcium from ER. Cyclosporine A, a calcineurin inhibitor, increased both [Ca(2+)](i) and the percentage of Cd-induced apoptosis. However, EGTA and the IP(3)R inhibitor, 2-APB, were able to partially modulate Cd cytotoxicity. These results led us to suggest that the extracellular and ER-released calcium plays a crucial role in Cd-induced apoptosis in mesangial cells. Following this line, we further detected the ER stress after Cd treatment since ER is one of the major calcium storage organelles. After Cd exposure, GADD153, a hallmark of ER stress, was upregulated (at 4h of exposure), followed by activation of ER-specific caspase-12 and its downstream molecule caspase-3 (at 16h of exposure). The pan caspase inhibitor, Z-VAD, and BAPTA-AM were able to reverse the Cd-induced cell death and ER stress, respectively. Furthermore, the mitochondrial membrane potential (DeltaPsi(m)) was depolarized significantly and cytochrome c was released after 24h of exposure to Cd and followed by mild activation of caspase-9 at the 36-h time point, indicating that mitochondria stress is a late event. Therefore, we concluded that ER is the major killer organelle in Cd-induced mesangial cell apoptosis and that calcium oscillation plays a pivotal role.


Sleep and body mass index in adolescence: results from a large population-based study of Norwegian adolescents aged 16 to 19 years.
The aim of this study was to examine the association between body mass index (BMI) and sleep duration, insomnia and symptoms of obstructive sleep apnea (OSA) in adolescents. Data were taken from a large population based study of 9,875 Norwegian adolescents aged 16-19. BMI was calculated from the self-reported body weight and categorized according to recommended age and gender specific cut offs for underweight, overweight and obesity. Detailed sleep parameters (sleep duration, insomnia, and OSA symptoms) were reported separately for weekdays and weekends. Data were analyzed using Pearson's chi-squared test and ANOVAs for simple categorical and continuous comparisons, and multinomial logistic regressions for analyses adjusting for known confounders. There was evidence for a curvilinear relationship between BMI and both sleep duration and insomnia for girls, whereas the relationship was linear for boys. Compared to the average weekday sleep duration among adolescents in the normal weight range (6 hrs 29 min), both underweight (5 hrs 48 min), overweight (6 hrs 13 min) and obese (5 hrs 57 min) adolescents had shorter sleep duration. OSA symptoms were linearly associated with BMI. Controlling for demographical factors as well as physical activity did not attenuate the associations. Additional adjustment for depression reduced the association between insomnia and obesity to a non-significant level. The evidence for a link between both underweight and overweight/obesity, and short sleep duration and OSA symptoms remained in the fully adjusted analyses. The associations were generally stronger for girls. This is one of the first population-based studies to investigate the relationship between sleep and BMI in adolescents while simultaneously controlling for important confounding factors. These findings require further research to investigate the temporal association between weights and sleep problems.


Cardiac physiology in transgenic mice.
By use of gene targeting and/or transgenesis, it is now possible to make defined changes in genes whose functions underlie mammalian cardiovascular function. Because of technical and economic considerations, these experiments are largely confined to the mouse. Genetic modification of the loci responsible for aspects of cardiac development, differentiation, and function via gene targeting, as well as modulation of the cardiac protein complement using transgenesis, has begun to provide mouse models of cardiac hypertrophy, dilated cardiomyopathy, and hypertrophic cardiomyopathies. In order to use these animal models fully and explore their phenotypes at the whole organ and whole animal levels, the extension of cardiovascular physiological methodologies to the mouse is imperative. Techniques for exploring aspects of cardiovascular function are well developed for larger animal models, but their modification for the small size of the mouse heart and for the animal's rapid cardiac cycle has proven to be a formidable challenge, requiring the combined efforts of the molecular biology, physiology, and cardiology communities. We review here the ability of present-day technology to obtain reproducible data on murine cardiac function at the whole organ and animal levels.


Mortality from cutaneous melanoma: evidence for contrasting trends between populations.
In recent years several reports have been published concerning trends in melanoma mortality in different countries, some of which have indicated that rates are beginning to fall. Many of these reports, however, have been based on small populations and have used different forms of statistical analysis. Our objective was to analyse systematically to what degree the epidemic of melanoma mortality had evolved similarly in different populations and whether there were any divergent trends that might increase our understanding. Instead of using all available data, we focused on countries with a minimum time series of 30 years and a minimum of 100 deaths annually in at least one sex from melanoma. We first inspected sex-specific age-standardized mortality rates and then performed age-period-cohort modelling. We found that the increase in mortality observed after 1950 was more pronounced in the age group 60-79. Statistical modelling showed a general increase in mortality rates in generations born after the turn of the century. Downturns in mortality, essentially in women and starting with generations born just before World War II, were found in Australia (where the earliest decreases were noted), the Nordic countries and the USA. Small decreases in rates in more recent generations were found in the UK and Canada. However, in France, Italy and Czechoslovakia, mortality rates were seen to be still increasing in recent cohorts. Our analysis suggests that populations are at different places on the melanoma mortality epidemic curve. The three trend patterns we observed are in agreement with time differences between populations with respect to the promotion of sun protection and the surveillance of pigmented skin lesions.


Scarcity frames value.
Economic models of decision making assume that people have a stable way of thinking about value. In contrast, psychology has shown that people's preferences are often malleable and influenced by normatively irrelevant contextual features. Whereas economics derives its predictions from the assumption that people navigate a world of scarce resources, recent psychological work has shown that people often do not attend to scarcity. In this article, we show that when scarcity does influence cognition, it renders people less susceptible to classic context effects. Under conditions of scarcity, people focus on pressing needs and recognize the trade-offs that must be made against those needs. Those trade-offs frame perception more consistently than irrelevant contextual cues, which exert less influence. The results suggest that scarcity can align certain behaviors more closely with traditional economic predictions.


Screening for Peripheral Artery Disease Using the Ankle-Brachial Index: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.
Peripheral artery disease (PAD) is associated with a high risk for cardiovascular events and poor ambulatory function, even in the absence of symptoms. Screening for PAD with the ankle-brachial index (ABI) may identify patients in need of treatment to improve health outcomes. To systematically review evidence for the US Preventive Services Task Force on PAD screening with the ABI, the diagnostic accuracy of the test, and the benefits and harms of treatment of screen-detected PAD. MEDLINE, PubMed, and the Cochrane Central Register of Controlled Trials for relevant English-language studies published between January 2012 and May 2, 2017. Surveillance continued through February 7, 2018. Studies of unselected or generally asymptomatic adults with no known cardiovascular disease. Independent critical appraisal and data abstraction by 2 reviewers. Cardiovascular morbidity; PAD morbidity; mortality; health-related quality of life; diagnostic accuracy; and serious adverse events. Five studies (N = 5864 participants) were included that examined the indirect evidence for the benefits and harms of screening and treatment of screen-detected PAD. No population-based screening trials evaluated the direct benefits or harms of PAD screening with the ABI alone. A single diagnostic accuracy study of the ABI compared with magnetic resonance angiography gold-standard imaging (n = 306) found low sensitivity (7%-34%) and high specificity (96%-100%) in a screening population. Two adequately powered trials (n = 4626) in asymptomatic populations with and without diabetes with a variably defined low ABI (≤0.95 or ≤0.99) showed no statistically significant effect of aspirin (100 mg daily) for composite CVD outcomes (adjusted hazard ratio [HR], 1.00 [95% CI, 0.81-1.23] and HR, 0.98 [95% CI, 0.76-1.26]). One trial (n = 3350) demonstrated no statistically significant increase in major bleeding events with the use of aspirin (adjusted HR, 1.71 [95% CI, 0.99- 2.97]) and no statistically significant increase in major gastrointestinal bleeding (relative risk, 1.13 [95% CI, 0.44-2.91]). Two exercise trials (n = 932) in screen-relevant populations reported no differences in quality of life, Walking Impairment Questionnaire walking distance, or symptoms at 12 and 52 weeks; no harms were reported. There was no direct evidence and limited indirect evidence on the benefits of PAD screening with the ABI in unselected or asymptomatic populations. Available studies suggest low sensitivity and lack of beneficial effect on health outcomes, but these studies have important limitations.


Properties of Evaporated SiO(2), SiO(x)N(y), and TiO(2), Films.
Films of SiO(2), SiO(x)N(y), and TiO(2), were prepared by reactive evaporation in ionized gases. Refractive index, absorptance, ir transmittance, stability, structure, and stress of these films were investigated. The SiO(2) films had the same refractive index as bulk quartz glass and an absorption coefficient of less than 40 cm(-1) at 190 nm. The internal stress in the SiO(2) films was considerably lower than that for silicon oxide films prepared by conventional reactive evaporation. SiO(x)N(y), films formed extremely smooth surfaces when heated in air after evaporation. On unheated substrates TiO(2) films with refractive indices up to 2.3 and an absorption coefficient of less than 40 cm(-1) at 633 nm were obtained. All films were x-ray amorphous and proved to be mechanically stable and water resistant.


Changes in causes of death among adults infected by HIV between 2000 and 2005: The "Mortalité 2000 and 2005" surveys (ANRS EN19 and Mortavic).
The multicenter national Mortalité 2005 survey aimed at describing the distribution of causes of death among HIV-infected adults in France in 2005 and its changes as compared with 2000. Physicians involved in the management of HIV infection notified deaths and documented the causes using a standardized questionnaire similar to the previous survey performed in 2000. Overall, 1042 deaths were notified in 2005 (vs 964 in 2000): with median age, 46 years (vs 41 years); men, 76%; and median last CD4 cell count, 161/mm (vs 94). The proportion of underlying causes of death due to AIDS decreased (36% in 2005 vs 47% in 2000), and the proportion of cancer not related to AIDS or hepatitis (17% vs 11%), liver related disease (15% vs 13%: hepatitis C, 11%, and hepatitis B, 2%), cardiovascular disease (8% vs 7%), or suicide (5% vs 4%) increased. Among the 375 AIDS-related deaths, the most frequent event was non-Hodgkin lymphoma (28%). Among cancers not related to AIDS or hepatitis, the most frequent localizations were lung (31%) and digestive tract (14%). Among the 154 liver-related deaths, 24% were due to hepatocarcinoma. The heterogeneity of causes of death among HIV-infected adults was confirmed and intensified in 2005, with 3 causes following AIDS: cancers and liver-related and cardiovascular diseases.


Mortality after admission for acute myocardial infarction in Aboriginal and non-Aboriginal people in New South Wales, Australia: a multilevel data linkage study.
Heart disease is a leading cause of the gap in burden of disease between Aboriginal and non-Aboriginal Australians. Our study investigated short- and long-term mortality after admission for Aboriginal and non-Aboriginal people admitted with acute myocardial infarction (AMI) to public hospitals in New South Wales, Australia, and examined the impact of the hospital of admission on outcomes. Admission records were linked to mortality records for 60047 patients aged 25-84 years admitted with a diagnosis of AMI between July 2001 and December 2008. Multilevel logistic regression was used to estimate adjusted odds ratios (AOR) for 30- and 365-day all-cause mortality. Aboriginal patients admitted with an AMI were younger than non-Aboriginal patients, and more likely to be admitted to lower volume, remote hospitals without on-site angiography. Adjusting for age, sex, year and hospital, Aboriginal patients had a similar 30-day mortality risk to non-Aboriginal patients (AOR: 1.07; 95% CI 0.83-1.37) but a higher risk of dying within 365 days (AOR: 1.34; 95% CI 1.10-1.63). The latter difference did not persist after adjustment for comorbid conditions (AOR: 1.12; 95% CI 0.91-1.38). Patients admitted to more remote hospitals, those with lower patient volume and those without on-site angiography had increased risk of short and long-term mortality regardless of Aboriginal status. Improving access to larger hospitals and those with specialist cardiac facilities could improve outcomes following AMI for all patients. However, major efforts to boost primary and secondary prevention of AMI are required to reduce the mortality gap between Aboriginal and non-Aboriginal people.


Ion pairing controls rheological properties of "processionary" polyelectrolyte hydrogels.
We demonstrated recently that polyelectrolytes with cationic moieties along the chain and a single anionic head are able to form physical hydrogels due to the reversible nature of the head-to-body ionic bond. Here we generate a variety of such polyelectrolytes with various cationic moieties and counterion combinations starting from a common polymeric platform. We show that the rheological properties (shear modulus, critical strain) of the final hydrogels can be modulated over three orders of magnitude depending on the cation/anion pair. Our data fit remarkably well within a scaling model involving a supramolecular head-to-tail single file between cross-links, akin to the behaviour of pine-processionary caterpillar. This model allows the quantitative measure of the amount of counterion condensation from standard rheology procedure.


The effect of pomegranate juice supplementation on strength and soreness after eccentric exercise.
The purpose of this study was to determine if pomegranate juice supplementation improved the recovery of skeletal muscle strength after eccentric exercise in subjects who routinely performed resistance training. Resistance trained men (n = 17) were randomized into a crossover design with either pomegranate juice or placebo. To produce delayed onset muscle soreness, the subjects performed 3 sets of 20 unilateral eccentric elbow flexion and 6 sets of 10 unilateral eccentric knee extension exercises. Maximal isometric elbow flexion and knee extension strength and muscle soreness measurements were made at baseline and 2, 24, 48, 72, 96, and 168 hours postexercise. Elbow flexion strength was significantly higher during the 2- to 168-hour period postexercise with pomegranate juice compared with that of placebo (main treatment effect; p = 0.031). Elbow flexor muscle soreness was also significantly reduced with pomegranate juice compared with that of placebo (main treatment effect; p = 0.006) and at 48 and 72 hours postexercise (p = 0.003 and p = 0.038, respectively). Isometric strength and muscle soreness in the knee extensors were not significantly different with pomegranate juice compared with those using placebo. Supplementation with pomegranate juice attenuates weakness and reduces soreness of the elbow flexor but not of knee extensor muscles. These results indicate a mild, acute ergogenic effect of pomegranate juice in the elbow flexor muscles of resistance trained individuals after eccentric exercise.


[Evaluation of acute hepatic failure treated at the Department of Medicine III, Kyushu University Hospital: indications for living-donor liver transplantation].
To evaluate indications for living-donor liver transplantation (LDLT), we examined 25 consecutive patients with acute hepatic failure admitted to the Department of Medicine III, Kyushu University Hospital between November 2001 and July 2004. These cases were diagnosed as fluminant hepatitis (n=13), severe-type acute hepatitis (n=11), or late-onset hepatic failure (n=1). Nine patients (36%) improved with conservative treatment (conservative treatment group), and the other 16 patients (64%) needed LDLT (LDLT indicated group). In the LDLT indicated group, 11 patients received LDLT, and 4 died because of lack of LDLT donors (n=3), or renal failure (n=1). The LDLT survival rate was 82% (9/11); two patients died due to hepatic infarction and brain edema, respectively. It is very important to predict whether a patient with acute hepatic failure belongs to the conservative treatment group or the LDLT indicated group on admission. Therefore, we analyzed variables that could influence prognosis, including, parameters of hepatic function and platelet counts on admission, and relative hepatic volume (%), which represents the ratio of hepatic volume measured by CT relative to standard hepatic volume calculated with body surface area. Univariate logistic analysis showed that relative hepatic volume, gammaglutamyl transpeptidase (gamma-GTP), alkaline phosphatase (ALP), and the ratio of direct bilirubin to total bilirubin (DB/TB) were significant predictors of survival (p < 0.05). Using these factors plus prothrombin time (PT) and total cholesterol, both of which were relatively significant predictors of survival (p < 0.2), we proposed a model for predicting the probability of survival by the stepwise method. Consequently, we proposed a model using four parameters: ALP, GGTP, PT, and relative hepatic volume (Volume) as shown below: p(%) = 1/(1+exp (-(-36.2375 + ALP x 0.0251 + gamma-GTP x 0.0102 + PT x 0.2558 + Volume 21.2158))) x 100. This model showed a significant correlation between prediction and consequence of survival (r2 = 0.7388, p = 0.0003). In conclusion, LDLT is an effective treatment for acute hepatic failure. The results of this study suggested that our model can adequately predict prognosis in the early phase of acute hepatic failure.


CSF tau/Abeta42 ratio for increased risk of mild cognitive impairment: a follow-up study.
Processes of Alzheimer disease (AD) likely begin years prior to the onset of cognitive impairment (latent AD), progress though a prodromal phase of mild cognitive impairment (MCI), and culminate in dementia. While many studies have evaluated CSF tau and Abeta(42) as biomarkers of the dementia or prodromal stages of AD, we are unaware of any study to evaluate these potential CSF biomarkers of latent AD. We determined the ratio of CSF tau/Abeta(42) (T/Abeta) using Luminex reagents in 129 control individuals that spanned from 21 to 100 years of age; for comparison we included patients with MCI (n = 12), probable AD (n = 21), or other neurodegenerative diseases (n = 12). We identified 16% of the control group with abnormally elevated CSF T/Abeta; all were 53 years or older. Using age-matched controls with normal CSF T/Abeta we showed that the high CSF T/Abeta subgroup of controls had significantly increased frequency of the epsilon4 allele of the apolipoprotein E gene and significantly increased risk of conversion to MCI during follow-up of up to 42 months suggesting that they had latent AD at the time of lumbar puncture. These generally applicable methods establish cutoff values to identify control individuals at increased risk of conversion to mild cognitive impairment which may be useful to people weighing the risk-benefit ratio of new preventive therapeutics and to researchers striving to enrich clinical trial populations with people with latent Alzheimer disease.


Medical costs of treating breast cancer among younger Medicaid beneficiaries by stage at diagnosis.
Younger women (aged 18-44 years) diagnosed with breast cancer often face more aggressive tumors, higher treatment intensity, and lower survival rates than older women. In this study, we estimated incident breast cancer costs by stage at diagnosis and by race for younger women enrolled in Medicaid. We analyzed cancer registry data linked to Medicaid claims in North Carolina from 2003 to 2008. We used Surveillance, Epidemiology, and End Results (SEER) Summary 2000 definitions for cancer stage. We split breast cancer patients into two cohorts: a younger and older group aged 18-44 and 45-64 years, respectively. We conducted a many-to-one match between patients with and without breast cancer using age, county, race, and Charlson Comorbidity Index. We calculated mean excess total cost of care between breast cancer and non-breast cancer patients. At diagnosis, younger women had a higher proportion of regional cancers than older women (49 vs. 42%) and lower proportions of localized cancers (44 vs. 50%) and distant cancers (7 vs. 9%). The excess costs of breast cancer (all stages) for younger and older women at 6 months after diagnosis were $37,114 [95% confidence interval (CI) = $35,769-38,459] and $28,026 (95% CI = $27,223-28,829), respectively. In the 6 months after diagnosis, the estimated excess cost was significantly higher to treat localized and regional cancer among younger women than among older women. There were no statistically significant differences in excess costs of breast cancer by race, but differences in treatment modality were present among younger Medicaid beneficiaries. Younger breast cancer patients not only had a higher prevalence of late-stage cancer than older women, but also had higher within-stage excess costs.


GDF15 is elevated in mice following retinal ganglion cell death and in glaucoma patients.
Glaucoma is the second leading cause of blindness worldwide. Physicians often use surrogate endpoints to monitor the progression of glaucomatous neurodegeneration. These approaches are limited in their ability to quantify disease severity and progression due to inherent subjectivity, unreliability, and limitations of normative databases. Therefore, there is a critical need to identify specific molecular markers that predict or measure glaucomatous neurodegeneration. Here, we demonstrate that growth differentiation factor 15 (GDF15) is associated with retinal ganglion cell death. Gdf15 expression in the retina is specifically increased after acute injury to retinal ganglion cell axons and in a murine chronic glaucoma model. We also demonstrate that the ganglion cell layer may be one of the sources of secreted GDF15 and that GDF15 diffuses to and can be detected in aqueous humor (AH). In validating these findings in human patients with glaucoma, we find not only that GDF15 is increased in AH of patients with primary open angle glaucoma (POAG), but also that elevated GDF15 levels are significantly associated with worse functional outcomes in glaucoma patients, as measured by visual field testing. Thus, GDF15 maybe a reliable metric of glaucomatous neurodegeneration, although further prospective validation studies will be necessary to determine if GDF15 can be used in clinical practice.


A Genetically Encoded Picolyl Azide for Improved Live Cell Copper Click Labeling.
Bioorthogonal chemistry allows rapid and highly selective reactivity in biological environments. The copper-catalyzed azide-alkyne cycloaddition (CuAAC) is a classic bioorthogonal reaction routinely used to modify azides or alkynes that have been introduced into biomolecules. Amber suppression is an efficient method for incorporating such chemical handles into proteins on the ribosome, in which noncanonical amino acids (ncAAs) are site specifically introduced into the polypeptide in response to an amber (UAG) stop codon. A variety of ncAA structures containing azides or alkynes have been proven useful for performing CuAAC chemistry on proteins. To improve CuAAC efficiency, biologically incorporated alkyne groups can be reacted with azide substrates that contain copper-chelating groups. However, the direct incorporation of copper-chelating azides into proteins has not been explored. To remedy this, we prepared the ncAA paz-lysine (PazK), which contains a picolyl azide motif. We show that PazK is efficiently incorporated into proteins by amber suppression in mammalian cells. Furthermore, PazK-labeled proteins show improved reactivity with alkyne reagents in CuAAC.


New developments in the theoretical treatment of low dimensional strongly correlated systems.
We review two important non-perturbative approaches for extracting the physics of low- dimensional strongly correlated quantum systems. Firstly, we start by providing a comprehensive review of non-Abelian bosonization. This includes an introduction to the basic elements of confor- mal field theory as applied to systems with a current algebra, and we orient the reader by presenting a number of applications of non-Abelian bosonization to models with large symmetries. We then tie this technique into recent advances in the ability of cold atomic systems to realize complex symme- tries. Secondly, we discuss truncated spectrum methods for the numerical study of systems in one and two dimensions. For one-dimensional systems we provide the reader with considerable insight into the methodology by reviewing canonical applications of the technique to the Ising model (and its variants) and the sine-Gordon model. Following this we review recent work on the development of renormalization groups, both numerical and analytical, that alleviate the effects of truncating the spectrum. Using these technologies, we consider a number of applications to one-dimensional systems: properties of carbon nanotubes, quenches in the Lieb-Liniger model, 1+1D quantum chro- modynamics, as well as Landau-Ginzburg theories. In the final part we move our attention to consider truncated spectrum methods applied to two-dimensional systems. This involves combining truncated spectrum methods with matrix product state algorithms. We describe applications of this method to two-dimensional systems of free fermions and the quantum Ising model, including their non-equilibrium dynamics.


Longevity genes: insights from calorie restriction and genetic longevity models.
In this review, we discuss the genes and the related signal pathways that regulate aging and longevity by reviewing recent findings of genetic longevity models in rodents in reference to findings with lower organisms. We also paid special attention to the genes and signals mediating the effects of calorie restriction (CR), a powerful intervention that slows the aging process and extends the lifespan in a range of organisms. An evolutionary view emphasizes the roles of nutrient-sensing and neuroendocrine adaptation to food shortage as the mechanisms underlying the effects of CR. Genetic and non-genetic interventions without CR suggest a role for single or combined hormonal signals that partly mediate the effect of CR. Longevity genes fall into two categories, genes relevant to nutrient-sensing systems and those associated with mitochondrial function or redox regulation. In mammals, disrupted or reduced growth hormone (GH)-insulin-like growth factor (IGF)-1 signaling robustly favors longevity. CR also suppresses the GH-IGF-1 axis, indicating the importance of this signal pathway. Surprisingly, there are very few longevity models to evaluate the enhanced anti-oxidative mechanism, while there is substantial evidence supporting the oxidative stress and damage theory of aging. Either increased or reduced mitochondrial function may extend the lifespan. The role of redox regulation and mitochondrial function in CR remains to be elucidated.


Maternal inheritance of mitochondria: implications for male fertility?
Evolutionary theory predicts maternal inheritance of the mitochondria will lead to the accumulation of mutations in the mitochondrial DNA (mtDNA) that impair male fertility, but leave females unaffected. The hypothesis has been referred to as 'Mother's Curse'. There are many examples of mtDNA mutations or haplotypes, in humans and other metazoans, associated with decreases in sperm performance, but seemingly few reports of associations involving female reproductive traits; an observation that has been used to support the Mother's Curse hypothesis. However, it is unclear whether apparent signatures of male bias in mitochondrial genetic effects on fertility reflect an underlying biological bias or a technical bias resulting from a lack of studies to have screened for female effects. Here, we conduct a systematic literature search of studies reporting mitochondrial genetic effects on fertility-related traits in gonochoristic metazoans (animals with two distinct sexes). Studies of female reproductive outcomes were sparse, reflecting a large technical sex bias across the literature. We were only able to make a valid assessment of sex specificity of mitochondrial genetic effects in 30% of cases. However, in most of these cases, the effects were male biased, including examples of male bias associated with mtDNA mutations in humans. These results are therefore consistent with the hypothesis that maternal inheritance has enriched mtDNA sequences with mutations that specifically impair male fertility. However, future research that redresses the technical imbalance in studies conducted per sex will be key to enabling researchers to fully assess the wider implications of the Mother's Curse hypothesis to male reproductive biology.


Intergenerational living arrangements in Myanmar and Thailand: a comparative analysis.
The present study compares living arrangements and related intergenerational support in Myanmar and Thailand based on recent national surveys of older persons in both countries and prior surveys in Thailand. The countries share relatively similar cultural contexts but differ radically in economic development. Substantially higher percentages of older persons in Myanmar currently coreside with their children and are considerably more likely to have non-coresident children living in the same locality. They are also less likely to live with a spouse and to have children living at a substantial distance. Older persons in Myanmar are much less likely to have phone contact with children living away and less likely to receive visits. Thai elders are considerably more likely to provide custodial care to grandchildren with absent parents and to live in skip generation households. Older Thais are also considerably more likely to receive substantial remittances from non-coresident children. The living arrangements of older age Thais in the past, however, more closely resembles the current situation in Myanmar. It appears that current differences are largely attributable to the more advanced Thai economic development through its associated impacts on migration, fertility and mortality. Contrasting political situations and government priorities also likely play a role. The results provide insights into the implications of development for older persons and suggest that if the recent course of political transformation and opening to the global economy continues in Myanmar, living arrangements there may well follow the trends in Thailand over past decades.


Leptin attenuates D2 receptor-mediated inhibition of putative ventral tegmental area dopaminergic neurons.
Obesity causes hyperleptinemia. We have previously shown that D2 receptor-mediated inhibition of ventral tegmental area (VTA) dopaminergic neurons is attenuated in diet-induced mice with obesity. Consequently, we hypothesized that high concentrations of serum leptin during obesity might modulate D2 receptor-mediated effects on VTA dopaminergic neurons. To investigate our hypothesis, we examined leptin effects on D2 receptor-mediated inhibition of putative VTA dopaminergic neurons from lean mice using electrophysiological techniques. Leptin (100 nmol/L) directly inhibited spontaneous firing in 71% of putative VTA dopaminergic neurons (leptin-responsive), whereas the remaining 29% of neurons were leptin-nonresponsive. In 41% of leptin-responsive neurons, leptin attenuated the reduced firing rate produced by quinpirole (100 nmol/L), whereas the remaining 59% of neurons exhibited no effect of leptin. In leptin-nonresponsive neurons, no significant leptin-induced effect was observed on reduced firing rate produced by quinpirole. In leptin-responsive neurons with positive leptin-induced attenuation of quinpirole effects, leptin-induced attenuation persisted for >20 min, whereas no such persistent attenuation was observed in other types of neurons. In conclusion, leptin attenuates D2 receptor-mediated inhibition in a subpopulation of putative VTA dopaminergic neurons. We suggest that leptin directly decreases, and indirectly increases, excitability of VTA dopaminergic neurons. In turn, this may contribute to a change in feeding behavior through the mesolimbic dopaminergic system during the development of obesity.


An ecosystem service perspective on urban nature, physical activity, and health.
Nature underpins human well-being in critical ways, especially in health. Nature provides pollination of nutritious crops, purification of drinking water, protection from floods, and climate security, among other well-studied health benefits. A crucial, yet challenging, research frontier is clarifying how nature promotes physical activity for its many mental and physical health benefits, particularly in densely populated cities with scarce and dwindling access to nature. Here we frame this frontier by conceptually developing a spatial decision-support tool that shows where, how, and for whom urban nature promotes physical activity, to inform urban greening efforts and broader health assessments. We synthesize what is known, present a model framework, and detail the model steps and data needs that can yield generalizable spatial models and an effective tool for assessing the urban nature-physical activity relationship. Current knowledge supports an initial model that can distinguish broad trends and enrich urban planning, spatial policy, and public health decisions. New, iterative research and application will reveal the importance of different types of urban nature, the different subpopulations who will benefit from it, and nature's potential contribution to creating more equitable, green, livable cities with active inhabitants.


Serotonin selectively influences moral judgment and behavior through effects on harm aversion.
Aversive emotional reactions to real or imagined social harms infuse moral judgment and motivate prosocial behavior. Here, we show that the neurotransmitter serotonin directly alters both moral judgment and behavior through increasing subjects' aversion to personally harming others. We enhanced serotonin in healthy volunteers with citalopram (a selective serotonin reuptake inhibitor) and contrasted its effects with both a pharmacological control treatment and a placebo on tests of moral judgment and behavior. We measured the drugs' effects on moral judgment in a set of moral 'dilemmas' pitting utilitarian outcomes (e.g., saving five lives) against highly aversive harmful actions (e.g., killing an innocent person). Enhancing serotonin made subjects more likely to judge harmful actions as forbidden, but only in cases where harms were emotionally salient. This harm-avoidant bias after citalopram was also evident in behavior during the ultimatum game, in which subjects decide to accept or reject fair or unfair monetary offers from another player. Rejecting unfair offers enforces a fairness norm but also harms the other player financially. Enhancing serotonin made subjects less likely to reject unfair offers. Furthermore, the prosocial effects of citalopram varied as a function of trait empathy. Individuals high in trait empathy showed stronger effects of citalopram on moral judgment and behavior than individuals low in trait empathy. Together, these findings provide unique evidence that serotonin could promote prosocial behavior by enhancing harm aversion, a prosocial sentiment that directly affects both moral judgment and moral behavior.


Structural Characterization of a Minimal Antibody against Human APOBEC3B.
APOBEC3B (A3B) is one of seven human APOBEC3 DNA cytosine deaminases that restrict viral infections as part of the overall innate immune response, but it also plays a major role in tumor evolution by mutating genomic DNA. Given the importance of A3B as a restriction factor of viral infections and as a driver of multiple human cancers, selective antibodies against A3B are highly desirable for its specific detection in various research and possibly diagnostic applications. Here, we describe a high-affinity minimal antibody, designated 5G7, obtained via a phage display screening against the C-terminal catalytic domain (ctd) of A3B. 5G7 also binds APOBEC3A that is highly homologous to A3Bctd but does not bind the catalytic domain of APOBEC3G, another Z1-type deaminase domain. The crystal structure of 5G7 shows a canonical arrangement of the heavy and light chain variable domains, with their complementarity-determining region (CDR) loops lining an antigen-binding cleft that accommodates a pair of α-helices. To understand the mechanism of A3Bctd recognition by 5G7, we used the crystal structures of A3Bctd and 5G7 as templates and computationally predicted the A3B-5G7 complex structure. Stable binding poses obtained by the simulation were further tested by site-directed mutagenesis and in vitro binding analyses. These studies mapped the epitope for 5G7 to a portion of C-terminal α6 helix of A3Bctd, with Arg374 playing an essential role. The same region of A3Bctd was used previously as a peptide antigen for generating a rabbit monoclonal antibody (mAb 5210-87-13), suggesting that this region is particularly immunogenic and that these antibodies from very different origins may share similar binding modes. Our studies provide a platform for the development of selective antibodies against A3B and other APOBEC3 family enzymes.


Category-length and category-strength effects using images of scenes.
Global matching models have provided an important theoretical framework for recognition memory. Key predictions of this class of models are that (1) increasing the number of occurrences in a study list of some items affects the performance on other items (list-strength effect) and that (2) adding new items results in a deterioration of performance on the other items (list-length effect). Experimental confirmation of these predictions has been difficult, and the results have been inconsistent. A review of the existing literature, however, suggests that robust length and strength effects do occur when sufficiently similar hard-to-label items are used. In an effort to investigate this further, we had participants study lists containing one or more members of visual scene categories (bathrooms, beaches, etc.). Experiments 1 and 2 replicated and extended previous findings showing that the study of additional category members decreased accuracy, providing confirmation of the category-length effect. Experiment 3 showed that repeating some category members decreased the accuracy of nonrepeated members, providing evidence for a category-strength effect. Experiment 4 eliminated a potential challenge to these results. Taken together, these findings provide robust support for global matching models of recognition memory. The overall list lengths, the category sizes, and the number of repetitions used demonstrated that scene categories are well-suited to testing the fundamental assumptions of global matching models. These include (A) interference from memories for similar items and contexts, (B) nondestructive interference, and (C) that conjunctive information is made available through a matching operation.


Smart pump technology: what we have learned.
Intravenous infusion may present the greatest preventable medication administration error risk to hospitalized patients. Smart pumps can provide clinical decision support at the bedside for nurses who are administering intravenously administered medications with the potential to significantly reduce medication errors and subsequent patient harm. However, implementations of smart pumps have yielded mixed results and mixed perceptions of their ability to actually decrease error. To realize the potential of smart pumps, there must exist a clear understanding of how these devices are being integrated into healthcare organizations, specifically nursing practice. The purpose of this article was to describe current smart pump evaluation studies and to suggest areas of future evaluation focus.


Differential contributions of BRCA1 and BRCA2 to early-onset breast cancer.
Germ-line mutations in the BRCA1 and BRCA2 genes predispose women to breast cancer. BRCA1 mutations are found in approximately 12 percent of women with breast cancer of early onset, and the specific mutation causing a deletion of adenine and guanine (185delAG), which is present in 1 percent of the Ashkenazi Jewish population, contributes to 21 percent of breast cancers among young Jewish women. The contribution of BRCA2 mutations to breast cancer of early onset is unknown. Lymphocyte specimens from 73 women with breast cancer diagnosed by the age of 32 were studied for heterozygous mutations of BRCA2 by a complementary-DNA-based protein-truncation assay, followed by automated nucleotide sequencing. In addition, specimens from 39 Jewish women with breast cancer diagnosed by the age of 40 were tested for specific mutations by an allele-specific polymerase chain reaction. Definite BRCA2 mutations were found in 2 of the 73 women with early-onset breast cancer (2.7 percent; 95 percent confidence interval, 0.4 to 9.6 percent), suggesting that BRCA2 is associated with fewer cases than BRCA1 (P=0.03). The specific BRCA2 mutation causing a deletion of thymine (6174delT), which is found in 1.3 percent of the Ashkenazi Jewish population, was observed in 1 of the 39 young Jewish women with breast cancer (2.6 percent; 95 percent confidence interval, 0.09 to 13.5 percent), indicating that it has a small role as a risk factor for early-onset breast cancer. Among young women with breast cancer, there are BRCA2 mutations that cause truncation of the extreme C terminus of the protein and that may be functionally silent, along with definite truncating mutations. Germ-line mutations in BRCA2 contribute to fewer cases of breast cancer among young women than do mutations in BRCA1. Carriers of BRCA2 mutations may have a smaller increase in the risk of early-onset breast cancer.


Coupling planar cell polarity signaling to morphogenesis.
Epithelial cells and other groups of cells acquire a polarity orthogonal to their apical-basal axes, referred to as Planar Cell Polarity (PCP). The process by which these cells become polarized requires a signaling pathway using Frizzled as a receptor. Responding cells sense cues from their environment that provide directional information, and they translate this information into cellular asymmetry. Most of what is known about PCP derives from studies in the fruit fly, Drosophila. We review what is known about how cells translate an unknown signal into asymmetric cytoskeletal reorganization. We then discuss how the vertebrate processes of convergent extension and cochlear hair-cell development may relate to Drosophila PCP signaling.


Early Human B Cell Response to Ebola Virus in Four U.S. Survivors of Infection.
The human B cell response to natural filovirus infections early after recovery is poorly understood. Previous serologic studies suggest that some Ebola virus survivors exhibit delayed antibody responses with low magnitude and quality. Here, we sought to study the population of individual memory B cells induced early in convalescence. We isolated monoclonal antibodies (MAbs) from memory B cells from four survivors treated for Ebola virus disease (EVD) 1 or 3 months after discharge from the hospital. At the early time points postrecovery, the frequency of Ebola-specific B cells was low and dominated by clones that were cross-reactive with both Ebola glycoprotein (GP) and with the secreted GP (sGP) form. Of 25 MAbs isolated from four donors, only one exhibited neutralization activity. This neutralizing MAb, designated MAb EBOV237, recognizes an epitope in the glycan cap of the surface glycoprotein. In vivo murine lethal challenge studies showed that EBOV237 conferred protection when given prophylactically at a level similar to that of the ZMapp component MAb 13C6. The results suggest that the human B cell response to EVD 1 to 3 months postdischarge is characterized by a paucity of broad or potent neutralizing clones. However, the neutralizing epitope in the glycan cap recognized by EBOV237 may play a role in the early human antibody response to EVD and should be considered in rational design strategies for new Ebola virus vaccine candidates.IMPORTANCE The pathogenesis of Ebola virus disease (EVD) in humans is complex, and the mechanisms contributing to immunity are poorly understood. In particular, it appears that the quality and magnitude of the human B cell response early after recovery from EVD may be reduced compared to most viral infections. Here, we isolated human monoclonal antibodies from B cells of four survivors of EVD at 1 or 3 months after hospital discharge. Ebola-specific memory B cells early in convalescence were low in frequency, and the antibodies they encoded demonstrated poor neutralizing potencies. One neutralizing antibody that protected mice from lethal infection, EBOV237, was identified in the panel of 25 human antibodies isolated. Recognition of the glycan cap epitope recognized by EBOV237 suggests that this antigenic site should be considered in vaccine design and treatment strategies for EVD.


The C-terminal 79 amino acids of the herpes simplex virus regulatory protein, Vmw65, efficiently activate transcription in yeast and mammalian cells in chimeric DNA-binding proteins.
Activation of herpes simplex virus immediate early gene expression normally requires the formation of a ternary complex between a virus trans-activator, Vmw65, a cellular octamer-binding protein, TRF and the cis-acting target sequence, the TAATGARAT motif. We report that the C-terminal 79 amino acids of Vmw65, which contain a potential acidic amphipathic helix, can activate transcription in both yeast and mammalian cells in the absence of TRF interaction when fused to the DNA-binding domain of the yeast transcription factor, GAL4. Together with our previous report which showed that the recruitment of TRF to the DNA by Vmw65 is insufficient for transcription activation, these results indicate that the octamer binding protein may not be directly involved in transcriptional induction mediated by Vmw65. The TRF-Vmw65 complex may therefore represent a novel class of transcription activator in which the protein domain responsible for sequence-specific DNA binding, present in TRF, and that necessary for induction of transcription, within Vmw65, are located on separate proteins. These results are discussed with reference to combinatorial transcriptional control and the role of octamer-binding proteins in other systems.


Toxic Tau Oligomers Modulated by Novel Curcumin Derivatives.
The pathological aggregation and accumulation of tau, a microtubule-associated protein, is a common feature amongst more than 18 different neurodegenerative diseases that are collectively known as tauopathies. Recently, it has been demonstrated that the soluble and hydrophobic tau oligomers are highly toxic in vitro due to their capacity towards seeding tau misfolding, thereby propagating the tau pathology seen across different neurodegenerative diseases. Modulating the aggregation state of tau oligomers through the use of small molecules could be a useful therapeutic strategy to target their toxicity, regardless of other factors involved in their formation. In this study, we screened and tested a small library of newly synthesized curcumin derivatives against preformed recombinant tau oligomers. Our results show that the curcumin derivatives affect and modulate the tau oligomer aggregation pathways, converting to a more aggregated non-toxic state as assessed in the human neuroblastoma SH-SY5Y cell line and primary cortical neuron cultures. These results provide insight into tau aggregation and may become a basis for the discovery of new therapeutic agents, as well as advance the diagnostic field for the detection of toxic tau oligomers.


What Happens to Patterns of Food Consumption when Food Prices Change? Evidence from A Systematic Review and Meta-Analysis of Food Price Elasticities Globally.
Recent years have seen considerable interest in examining the impact of food prices on food consumption and subsequent health consequences. Fiscal policies targeting the relative price of unhealthy foods are frequently put forward as ways to address the obesity epidemic. Conversely, various food subsidy interventions are used in attempts to reduce levels of under-nutrition. Information on price elasticities is essential for understanding how such changes in food prices affect food consumption. It is crucial to know not only own-price elasticities but also cross-price elasticities, as food substitution patterns may have significant implications for policy recommendations. While own-price elasticities are common in analyses of the impact of food price changes on health, cross-price effects, even though generally acknowledged, are much less frequently included in analyses, especially in the public health literature. This article systematically reviews the global evidence on cross-price elasticities and provides combined estimates for seven food groups in low-income, middle-income and high-income countries alongside previously estimated own-price elasticities. Changes in food prices had the largest own-price effects in low-income countries. Cross-price effects were more varied and depending on country income level were found to be reinforcing, undermining or alleviating own-price effects.


Fixation with bioabsorbable screws for the treatment of fractures of the ankle.
One hundred and fifty-five patients who had a closed, displaced medial malleolar, bimalleolar, or trimalleolar fracture of the ankle were managed with medial malleolar fixation with use of either 4.0-millimeter orientruded polylactide screws (eighty-three patients, study group) or 4.0-millimeter stainless-steel screws (seventy-two patients, control group). All lateral malleolar fractures were stabilized with standard metallic implants. At an average of thirty-seven months (range, twenty-one to fifty-nine months), the radiographic and functional results in the two groups were equivalent. Differences between the two groups with regard to the rates of operative and postoperative complications were not statistically significant. Late spontaneous drainage of the hydrolyzed polylactide was not noted in any patient in the study group. The prevalence of late tenderness over the medial malleolar implant was lower in the patients in whom the fracture had been stabilized with polylactide screws. We conclude that polylactide screws are a safe and effective alternative to stainless-steel screws for the fixation of displaced medial malleolar fractures.


Do we need an irritable subtype of ADHD? Replication and extension of a promising temperament profile approach to ADHD subtyping.
Attention deficit hyperactivity disorder (ADHD) is emblematic of unresolved heterogeneity in psychiatric disorders-the variation in biological, clinical, and psychological correlates that impedes progress on etiology. One approach to this problem is to characterize subgroups using measures rooted in biological or psychological theory, consistent with the National Institute of Mental Health's research domain criteria initiative. Within ADHD, a promising application involves using emotion trait profiles that can address the role of irritability as a complicating feature for ADHD. Here, a new sample of 186 children with ADHD was evaluated using community detection analysis to determine if meaningful subprofiles existed and if they replicated those previously identified. The new sample and a prior sample were pooled for evaluation of (a) method dependence, (b) longitudinal assessment of the stability of classifications, and (c) clinical prediction 2 years later. Three temperament profiles were confirmed within the ADHD group: one with normative emotional functioning ("mild"), one with high surgency ("surgent"), and one with high negative affect ("irritable"). Profiles were similar across statistical clustering approaches. The irritable group had the highest external validity: It was moderately stable over time and it enhanced prospective prediction of clinical outcomes beyond standard baseline indicators. The irritable group was not reducible to ADHD + oppositional defiant disorder, ADHD + disruptive mood dysregulation disorder, or other patterns of comorbidity. Among the negative affect domains studied, trait proneness to anger uniquely contributed to clinical prediction. Results extend our understanding of chronic irritability in psychiatric disorders and provide prospects for a fresh approach to assessing ADHD heterogeneity focused on the distinction between ADHD with and without anger/irritability. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Association between time interval to publication and statistical significance.
Studies have shown that reports from clinical trials with statistically significant results tend to be submitted and published more rapidly than reports from studies with null or insignificant findings. We wanted to determine whether manuscripts reporting positive results from controlled clinical trials are published more quickly than those reporting negative results. We tracked manuscripts from submission to JAMA until the publication decision. We classified results as positive if a statistically significant difference was reported for the primary outcome. Manuscripts were further classified according to indicators of methodologic quality and other study characteristics. We included manuscripts if they were submitted from February 1996 through August 1999, reported results of a prospective study in which participants were assigned to a treatment or comparison group, used statistical tests to compare differences between groups, and were accepted for publication. One hundred thirty-three manuscripts met our inclusion criteria, 78 (59%) reported positive results, 51 (38%) reported negative results. We were unable to classify the direction of results for 4 articles (3%). The time interval between submission and publication was not associated with positive results: median time between submission and publication was 7.8 months for reports with positive vs 7.6 months for reports with negative results (P =.44). Time to publication also was not associated with any marker of study quality or study characteristic. Among 133 published controlled trials, time to publication was not associated with statistical significance, methodologic quality, or other study characteristics.


Rapid ionic modifications during the aequorin-detected calcium transient in a skinned canine cardiac Purkinje cell.
A microprocessor-controlled system of microinjections and microaspirations has been developed to change, within approximately 1 ms, the [free Ca2+] at the outer surface of the sarcoplasmic reticulum (SR) wrapped around individual myofibrils (0.3-0.4 micron radius) of a skinned canine cardiac Purkinje cell (2.5-4.5 micron overall radius) at different phases of a Ca2+ transient. Simultaneously monitoring tension and aequorin bioluminescence provided two methods for estimating the peak myoplasmic [free Ca2+] reached during the spontaneous cyclic Ca2+ release from the SR obtained in the continuous presence of a bulk solution [free Ca2+] sufficiently high to overload the SR. These methods gave results in excellent agreement for the spontaneous Ca2+ release under a variety of conditions of pH and [free Mg2+], and of enhancement of Ca2+ release by calmodulin. Disagreement was observed, however, when the Ca2+ transient was modified during its ascending phase. The experiments also permitted quantification of the aequorin binding within the myofibrils and determination of its operational apparent affinity constant for Ca2+ at various [free Mg2+] levels. An increase of [free Ca2+] at the outer surface of the SR during the ascending phase of the Ca2+ transient induced further release of Ca2+. In contrast, an increase of [free Ca2+] during the descending phase of the Ca2+ transient did not cause further Ca2+ release. Varying [free H+], [free Mg2+], or the [Na+]/[K+] ratio had no significant effect on the Ca2+ transient during which the modification was applied, but it altered the subsequent Ca2+ transient. Therefore, Ca2+ appears to be the major, if not the only, ion controlling Ca2+ release from the SR rapidly enough to alter a Ca2+ transient during its course.


On having royal relatives: Interpreting misidentifications in a case of impaired person recognition.
We report data from a patient, NE, who after surviving encephalitis made misidentification responses to faces known to her premorbidly. NE frequently mistook one famous person for another, one relative for another, and, under some conditions, believed that a picture of a famous person actually depicted one of her relatives. Unlike previously reported patients who have misidentified faces, NE (1) performed reasonably well on tests of facial perception, (2) showed no obvious executive deficits in tests of frontal lobe function, and (3) showed an ability to constrain her misidentification responses in certain situations. A cognitive neuropsychological investigation revealed that NE was able to judge misidentified faces as familiar but failed to access precise semantic information. There were also semantic deficits when knowledge of people was probed through nonvisual modalities-for example, when naming people from definition. We argue that a semantic, as opposed to executive, deficit plays the major (though probably not sole) role in NE's misidentification responses, and we consider how the inter-active activation model of face recognition (Burton, Bruce, & Johnston, 1990) can account for such disorders of person recognition more comprehensively than the Bruce and Young (1986) model.


Potential kidney toxicity from the antiviral drug tenofovir: new indications, new formulations, and a new prodrug.
The antiviral agent tenofovir is highly effective for the treatment of HIV and hepatitis B virus infections, and the older prodrug tenofovir disoproxil fumarate (TDF) is also a component of daily preexposure prophylaxis (PrEP) to reduce the risk of HIV infection in high-risk populations. Although TDF is well tolerated, the potential for kidney and bone toxicity has important implications for public health given the large number of individuals exposed to TDF worldwide. This review summarizes the recent literature on kidney and bone health in individuals treated with TDF and the newer prodrug tenofovir alafenamide (TAF). Risk factors for TDF toxicity appear to be similar in patients treated for HIV or hepatitis B virus and in HIV-uninfected PrEP users, although drug-drug interactions are a more important concern in HIV-positive individuals. The risk of toxicity appears to be lower with TAF, but further studies are needed to confirm the safety of long-term use and to evaluate the efficacy of TAF-based PrEP. Nephrologists should be aware of the potential kidney and bone toxicity of TDF, as well as unique situations in which the newer prodrug TAF may contribute to kidney injury.


Comparison of Leaf Sheath Transcriptome Profiles with Physiological Traits of Bread Wheat Cultivars under Salinity Stress.
Salinity stress has significant negative effects on plant biomass production and crop yield. Salinity tolerance is controlled by complex systems of gene expression and ion transport. The relationship between specific features of mild salinity stress adaptation and gene expression was analyzed using four commercial varieties of bread wheat (Triticum aestivum) that have different levels of salinity tolerance. The high-throughput phenotyping system in The Plant Accelerator at the Australian Plant Phenomics Facility revealed variation in shoot relative growth rate and salinity tolerance among the four cultivars. Comparative analysis of gene expression in the leaf sheaths identified genes whose functions are potentially linked to shoot biomass development and salinity tolerance. Early responses to mild salinity stress through changes in gene expression have an influence on the acquisition of stress tolerance and improvement in biomass accumulation during the early "osmotic" phase of salinity stress. In addition, results revealed transcript profiles for the wheat cultivars that were different from those of usual stress-inducible genes, but were related to those of plant growth. These findings suggest that, in the process of breeding, selection of specific traits with various salinity stress-inducible genes in commercial bread wheat has led to adaptation to mild salinity conditions.


Time-dependent expression of Arc and zif268 after acquisition of fear conditioning.
Memory consolidation requires transcription and translation of new protein. Arc, an effector immediate early gene, and zif268, a regulatory transcription factor, have been implicated in synaptic plasticity underlying learning and memory. This study explored the temporal expression profiles of these proteins in the rat hippocampus following fear conditioning. We observed a time-dependent increase of Arc protein in the dorsal hippocampus 30-to-90-minute post training, returning to basal levels at 4 h. Zif268 protein levels, however, gradually increased at 30-minute post training before peaking in expression at 60 minute. The timing of hippocampal Arc and zif268 expression coincides with the critical period for protein synthesis-dependent memory consolidation following fear conditioning. However, the expression of Arc protein appears to be driven by context exploration, whereas, zif268 expression may be more specifically related to associative learning. These findings suggest that altered Arc and zif268 expression are related to neural plasticity during the formation of fear memory.


Bristle Maps: a multivariate abstraction technique for geovisualization.
We present Bristle Maps, a novel method for the aggregation, abstraction, and stylization of spatiotemporal data that enables multiattribute visualization, exploration, and analysis. This visualization technique supports the display of multidimensional data by providing users with a multiparameter encoding scheme within a single visual encoding paradigm. Given a set of geographically located spatiotemporal events, we approximate the data as a continuous function using kernel density estimation. The density estimation encodes the probability that an event will occur within the space over a given temporal aggregation. These probability values, for one or more set of events, are then encoded into a bristle map. A bristle map consists of a series of straight lines that extend from, and are connected to, linear map elements such as roads, train, subway lines, and so on. These lines vary in length, density, color, orientation, and transparency—creating the multivariate attribute encoding scheme where event magnitude, change, and uncertainty can be mapped as various bristle parameters. This approach increases the amount of information displayed in a single plot and allows for unique designs for various information schemes. We show the application of our bristle map encoding scheme using categorical spatiotemporal police reports. Our examples demonstrate the use of our technique for visualizing data magnitude, variable comparisons, and a variety of multivariate attribute combinations. To evaluate the effectiveness of our bristle map, we have conducted quantitative and qualitative evaluations in which we compare our bristle map to conventional geovisualization techniques. Our results show that bristle maps are competitive in completion time and accuracy of tasks with various levels of complexity.


Neutralizing antibodies to an immunodominant envelope sequence do not prevent gp120 binding to CD4.
Animals immunized with the human immunodeficiency virus type 1 gp160 glycoprotein or certain recombinant envelope components develop potent virus-neutralizing activity. This activity is principally due to antibodies directed toward a hypervariable region of gp120 between cysteine residues 302 and 337 and is virus isolate specific. These antisera, as well as two neutralizing monoclonal antibodies directed against the same hypervariable sequence, do not appreciably block gp120 from binding CD4. In contrast, serum samples from infected humans possess high titers of antibodies that block gp120-CD4 binding; these titers approximately correlate with the serum neutralization titers. Our results suggest that there are at least two targets on the envelope glycoprotein for virus neutralization. The target responsible for the broader neutralizing activity of human serum may be a conserved region of gp120 involved in CD4 binding. The antibodies directed at the hypervariable region of the envelope inhibit a different step in virus infection which is subsequent to receptor binding. The extent to which these two different epitopes of gp120 may be involved in protection against human immunodeficiency virus infection is discussed.


Access to alcohol and heart disease among patients in hospital: observational cohort study using differences in alcohol sales laws.
To investigate the relation between alcohol consumption and heart disease by using differences in county level alcohol sales laws as a natural experiment. Observational cohort study using differences in alcohol sales laws. Hospital based healthcare encounters in Texas, USA. 1 106 968 patients aged 21 or older who were residents of "wet" (no alcohol restrictions) and "dry" (complete prohibition of alcohol sales) counties and admitted to hospital between 2005 and 2010, identified using the Texas Inpatient Research Data File. Prevalent and incident alcohol misuse and alcoholic liver disease were used for validation analyses. The main cardiovascular outcomes were atrial fibrillation, acute myocardial infarction, and congestive heart failure. Residents of wet counties had a greater prevalence and incidence of alcohol misuse and alcoholic liver disease. After multivariable adjustment, wet county residents had a greater prevalence (odds ratio 1.05, 95% confidence interval 1.01 to 1.09; P=0.007) and incidence (hazard ratio 1.07, 1.01 to 1.13; P=0.014) of atrial fibrillation, a lower prevalence (odds ratio 0.83, 0.79 to 0.87; P<0.001) and incidence (hazard ratio 0.91, 0.87 to 0.99; P=0.019) of myocardial infarction, and a lower prevalence (odds ratio 0.87, 0.84 to 0.90; P<0.001) of congestive heart failure. Conversion of counties from dry to wet resulted in statistically significantly higher rates of alcohol misuse, alcoholic liver disease, atrial fibrillation, and congestive heart failure, with no detectable difference in myocardial infarction. Greater access to alcohol was associated with more atrial fibrillation and less myocardial infarction and congestive heart failure, although an increased risk of congestive heart failure was seen shortly after alcohol sales were liberalized.


Can it be harmful for parents to talk to their child about their weight? A meta-analysis.
Many parents express concern that raising the issue of weight risks harming their child's physical self-perceptions and wellbeing. Such concerns can deter families from engaging with weight management services. This systematic review aimed to investigate the evidence behind these concerns by analysing the association between parent-child weight-talk and child wellbeing. A systematic search of eight databases identified four intervention studies and 38 associative studies. Meta-analysis was only possible for the associative studies; to facilitate more meaningful comparisons, weight-talk was categorized into four communication types and effect size estimates for the association between these and wellbeing indicators were calculated through a random effects model. Encouraging children to lose weight and criticizing weight were associated with poorer physical self-perceptions and greater dieting and dysfunctional eating (effect sizes: 0.20 to 0.47). Conversely, parental encouragement of healthy lifestyles without explicit reference to weight was associated with better wellbeing, but this was only measured in two studies. Of the four intervention studies, only one isolated the effects of parents' communication on wellbeing outcomes, reporting a positive effect. There was no effect of age on the strength of associations, but dysfunctional eating was more strongly associated with parent communication for girls than boys. The findings indicate that some forms of parent-child weight-talk are associated with poor wellbeing, but suggest that this is not inevitable. Encouraging healthy behaviours without reference to weight-control, and positive parental involvement in acknowledging and addressing weight-concern may avoid such outcomes. More longitudinal research is needed to analyse the direction of these effects.


Abortion surveillance--United States, 2002.
CDC began abortion surveillance in 1969 to document the number and characteristics of women obtaining legal induced abortions. This report summarizes and describes data voluntarily reported to CDC regarding legal induced abortions obtained in the United States in 2002. For each year since 1969, CDC has compiled abortion data by state or area of occurrence. During 1973-1997, data were received from or estimated for 52 reporting areas in the United States: 50 states, the District of Columbia, and New York City. In 1998 and 1999, CDC compiled abortion data from 48 reporting areas. Alaska, California, New Hampshire, and Oklahoma did not report, and data for these states were not estimated. For 2000-2002, Oklahoma again reported these data, increasing the number of reporting areas to 49. A total of 854,122 legal induced abortions were reported to CDC for 2002 from 49 reporting areas, representing a 0.1% increase from the 853,485 legal induced abortions reported by the same 49 reporting areas for 2001. The abortion ratio, defined as the number of abortions per 1,000 live births, was 246 in 2002, the same as reported for 2001. The abortion rate was 16 per 1,000 women aged 15-44 years for 2002, the same as for 2001. For the same 48 reporting areas, the abortion rate remained relatively constant during 1997-2002. The highest percentages of reported abortions were for women who were unmarried (82%), white (55%), and aged <25 years (51%). Of all abortions for which gestational age was reported, 60% were performed at < or =8 weeks' gestation and 88% at <13 weeks. From 1992 (when detailed data regarding early abortions were first collected) through 2002, steady increases have occurred in the percentage of abortions performed at < or =6 weeks' gestation. A limited number of abortions was obtained at >15 weeks' gestation, including 4.1% at 16-20 weeks and 1.4% at > or =21 weeks. A total of 35 reporting areas submitted data stating that they performed and enumerated medical (nonsurgical) procedures, accounting for 5.2% of all known reported procedures from the 45 areas with adequate reporting on type of procedure. During 1990-1997, the number of legal induced abortions gradually declined. When the same 48 reporting areas were compared, the number of abortions decreased during 1996-2001, then slightly increased in 2002. In 2000 and 2001, even with one additional reporting state, the number of abortions declined slightly, with a minimal increase in 2002. Abortion surveillance in the United States continues to provide the data necessary for examining trends in numbers and characteristics of women who obtain legal induced abortions and to increase understanding of this pregnancy outcome. Policymakers and program planners use these data to improve the health and well-being of women and infants.


Effect of propranolol therapy on aldosterone responses to angiotensin II and adrenocorticotropic hormone in essential hypertension.
1. The plasma aldosterone responses to exogenous angiotensin II and adrenocorticotropic hormone (ACTH) were studied before and after 1 month of propranolol therapy (120-240 mg/day) in eight patients with essential hypertension. 2. Basal supine plasma renin activity was decreased (P less than 0.001) after propranolol, whereas plasma aldosterone was unchanged. After 3 h of upright posture the increases in both plasma renin activity and aldosterone were decreased (P less than 0.05) after propranolol. 3. Plasma aldosterone responses to exogenous angiotensin II and ACTH were not significantly different after propranolol. Serum and urinary electrolytes and plasma cortisol were also unaffected by propranolol therapy. 4. It is concluded that changes in adrenal sensitivity are not responsible for maintaining unchanged supine plasma aldosterone concentrations after beta-adrenoceptor antagonism in essential hypertension.