Modelling competition and dispersal in a statistical phylogeographic framework.
Competition between organisms influences the processes governing the colonization of new habitats. As a consequence, species or populations arriving first at a suitable location may prevent secondary colonization. Although adaptation to environmental variables (e.g., temperature, altitude, etc.) is essential, the presence or absence of certain species at a particular location often depends on whether or not competing species co-occur. For example, competition is thought to play an important role in structuring mammalian communities assembly. It can also explain spatial patterns of low genetic diversity following rapid colonization events or the "progression rule" displayed by phylogenies of species found on archipelagos. Despite the potential of competition to maintain populations in isolation, past quantitative analyses have largely ignored it because of the difficulty in designing adequate methods for assessing its impact. We present here a new model that integrates competition and dispersal into a Bayesian phylogeographic framework. Extensive simulations and analysis of real data show that our approach clearly outperforms the traditional Mantel test for detecting correlation between genetic and geographic distances. But most importantly, we demonstrate that competition can be detected with high sensitivity and specificity from the phylogenetic analysis of genetic variation in space.


Comparison of machine learning classifiers for influenza detection from emergency department free-text reports.
Influenza is a yearly recurrent disease that has the potential to become a pandemic. An effective biosurveillance system is required for early detection of the disease. In our previous studies, we have shown that electronic Emergency Department (ED) free-text reports can be of value to improve influenza detection in real time. This paper studies seven machine learning (ML) classifiers for influenza detection, compares their diagnostic capabilities against an expert-built influenza Bayesian classifier, and evaluates different ways of handling missing clinical information from the free-text reports. We identified 31,268 ED reports from 4 hospitals between 2008 and 2011 to form two different datasets: training (468 cases, 29,004 controls), and test (176 cases and 1620 controls). We employed Topaz, a natural language processing (NLP) tool, to extract influenza-related findings and to encode them into one of three values: Acute, Non-acute, and Missing. Results show that all ML classifiers had areas under ROCs (AUC) ranging from 0.88 to 0.93, and performed significantly better than the expert-built Bayesian model. Missing clinical information marked as a value of missing (not missing at random) had a consistently improved performance among 3 (out of 4) ML classifiers when it was compared with the configuration of not assigning a value of missing (missing completely at random). The case/control ratios did not affect the classification performance given the large number of training cases. Our study demonstrates ED reports in conjunction with the use of ML and NLP with the handling of missing value information have a great potential for the detection of infectious diseases.


Web GIS in practice VII: stereoscopic 3-D solutions for online maps and virtual globes.
Because our pupils are about 6.5 cm apart, each eye views a scene from a different angle and sends a unique image to the visual cortex, which then merges the images from both eyes into a single picture. The slight difference between the right and left images allows the brain to properly perceive the 'third dimension' or depth in a scene (stereopsis). However, when a person views a conventional 2-D (two-dimensional) image representation of a 3-D (three-dimensional) scene on a conventional computer screen, each eye receives essentially the same information. Depth in such cases can only be approximately inferred from visual clues in the image, such as perspective, as only one image is offered to both eyes. The goal of stereoscopic 3-D displays is to project a slightly different image into each eye to achieve a much truer and realistic perception of depth, of different scene planes, and of object relief. This paper presents a brief review of a number of stereoscopic 3-D hardware and software solutions for creating and displaying online maps and virtual globes (such as Google Earth) in "true 3D", with costs ranging from almost free to multi-thousand pounds sterling. A practical account is also given of the experience of the USGS BRD UMESC (United States Geological Survey's Biological Resources Division, Upper Midwest Environmental Sciences Center) in setting up a low-cost, full-colour stereoscopic 3-D system.


The interaction between dietary fructose and magnesium adversely affects macromineral homeostasis in men.
Studies with rats have found that an interaction between fructose and magnesium affects macromineral metabolism; high dietary fructose significantly increased kidney calcification in both male and female rats, particularly when dietary magnesium was low. This study tests the hypothesis that an interaction between dietary fructose and magnesium adversely affects macromineral homeostasis in men. Eleven men aged 22 to 40 years were fed a mixed, Western diet for four 42-day dietary periods in which dietary magnesium was either approximately 170 or 370 mg/day and dietary fructose was either 4% or 20% of energy. A decaffeinated beverage containing high fructose corn syrup replaced cornstarch, bread and rice in the low fructose diet to give the high fructose diet. High dietary fructose significantly (p<0.01) increased magnesium balance during both low and high dietary magnesium intakes. Ultrafilterable and ionized serum magnesium also apparently were related to magnesium and fructose intakes; they were higher when fructose was fed and when Mg intakes were high. High fructose depressed calcium balance: the effect tended to be more marked when dietary Mg was low. High dietary fructose also significantly (p<0.005) decreased phosphorous balance. Urinary phosphorous losses were significantly (p<0.001) higher when high dietary fructose was fed. High dietary fructose also increased the concentration of serum alkaline phosphatase (p<0.005). These findings indicate that dietary fructose adversely affects macromineral homeostasis in humans and suggest further studies to see if a high fructose diet coupled with low dietary magnesium and marginal calcium leads to bone loss.


Separation of plasmid DNA isoforms by highly converging flow through small membrane pores.
Plasmid DNA isoforms can be separated by both agarose gel electrophoresis and a variety of chromatographic methods, but both of these approaches have significant shortcomings in terms of scalability, throughput, and/or resolution. This study provides the first demonstration that the supercoiled, linear, and open-circular isoforms of plasmid DNA can be effectively separated based on differences in their elongational flexibility in the highly converging flow field that is established during membrane ultrafiltration. Data were obtained with plasmids from 3 to 17 kbp in size using commercially available cellulose ultrafiltration membranes with pores an order of magnitude smaller than the DNA root-mean-square radius of gyration. High-resolution separations were achieved by controlling the filtrate flux between the critical flux values required for transmission of the individual isoforms. The separation behavior in ultrafiltration was very different than that observed in size exclusion chromatography or agarose gel electrophoresis due to differences in the underlying separation mechanisms. The simplicity of the ultrafiltration process makes this approach attractive for a wide range of applications, including large-scale purification of plasmid DNA for gene therapy.


Disparities in the evaluation and diagnosis of abuse among infants with traumatic brain injury.
To evaluate in a national database the association of race and socioeconomic status with radiographic evaluation and subsequent diagnosis of child abuse after traumatic brain injury (TBI) in infants. We conducted a retrospective study of infants with non-motor vehicle-associated TBI who were admitted to 39 pediatric hospitals from January 2004 to June 2008. Logistic regression controlling for age, type, and severity of TBI and the presence of other injuries was performed to examine the association of race and socioeconomic status with the principal outcomes of radiographic evaluation for suspected abuse and diagnosis of abuse. Regression coefficients were transformed to probabilities. After adjustment for type and severity of TBI, age, and other injuries, publicly insured/uninsured infants were more likely to have had skeletal surveys performed than were privately insured infants (81% vs 59%). The difference in skeletal survey performance for infants with public or no insurance versus private insurance was greater among white (82% vs 53%) infants than among black (85% vs 75%) or Hispanic (72% vs 55%) infants (P=.022). Although skeletal surveys were performed in a smaller proportion of white than black or Hispanic infants, the adjusted probability for diagnosis of abuse among infants evaluated with a skeletal survey was higher among white infants (61%) than among black (51%) or Hispanic (53%) infants (P=.009). National data suggest continued biases in the evaluation for abusive head trauma. The conflicting observations of fewer skeletal surveys among white infants and higher rates of diagnosis among those screened elicit concern for overevaluation in some infants (black or publicly insured/uninsured) or underevaluation in others (white or privately insured).


The progressive nature of Wallerian degeneration in wild-type and slow Wallerian degeneration (WldS) nerves.
The progressive nature of Wallerian degeneration has long been controversial. Conflicting reports that distal stumps of injured axons degenerate anterogradely, retrogradely, or simultaneously are based on statistical observations at discontinuous locations within the nerve, without observing any single axon at two distant points. As axon degeneration is asynchronous, there are clear advantages to longitudinal studies of individual degenerating axons. We recently validated the study of Wallerian degeneration using yellow fluorescent protein (YFP) in a small, representative population of axons, which greatly improves longitudinal imaging. Here, we apply this method to study the progressive nature of Wallerian degeneration in both wild-type and slow Wallerian degeneration (WldS) mutant mice. In wild-type nerves, we directly observed partially fragmented axons (average 5.3%) among a majority of fully intact or degenerated axons 37-42 h after transection and 40-44 h after crush injury. Axons exist in this state only transiently, probably for less than one hour. Surprisingly, axons degenerated anterogradely after transection but retrogradely after a crush, but in both cases a sharp boundary separated intact and fragmented regions of individual axons, indicating that Wallerian degeneration progresses as a wave sequentially affecting adjacent regions of the axon. In contrast, most or all WldS axons were partially fragmented 15-25 days after nerve lesion, WldS axons degenerated anterogradely independent of lesion type, and signs of degeneration increased gradually along the nerve instead of abruptly. Furthermore, the first signs of degeneration were short constrictions, not complete breaks. We conclude that Wallerian degeneration progresses rapidly along individual wild-type axons after a heterogeneous latent phase. The speed of progression and its ability to travel in either direction challenges earlier models in which clearance of trophic or regulatory factors by axonal transport triggers degeneration. WldS axons, once they finally degenerate, do so by a fundamentally different mechanism, indicated by differences in the rate, direction and abruptness of progression, and by different early morphological signs of degeneration. These observations suggest that WldS axons undergo a slow anterograde decay as axonal components are gradually depleted, and do not simply follow the degeneration pathway of wild-type axons at a slower rate.


Good things come in threes: single-parent multigenerational family structure and adolescent adjustment.
Using data from the National Educational Longitudinal Study (NELS), we found that teenagers who live in nonmarried families are less likely to graduate from high school or to attend college, more likely to smoke or drink, and more likely to initiate sexual activity. Not all nonmarried families are alike, however. In particular, teenagers living with their single mothers and with at least one grandparent in multigenerational households have developmental outcomes that are at least as good and often better than the outcomes of teenagers in married families. These findings obtain when a wide array of economic resources, parenting behavior, and home and school characteristics are controlled for.


Controlled study on the therapeutic efficacy of propionyl-L-carnitine in patients with congestive heart failure.
A double-blind phase II study of propionyl-L-carnitine (CAS 17298-37-2) versus placebo was carried out on a group of 60 patients with mild to moderate (II and III NYHA class) congestive heart failure. The group was made up of men and women aged between 48 and 73 years in chronic treatment with digitalis and diuretics for at least 3 months and who still displayed symptoms. Thirty of these patients were chosen randomly and for 180 days, 500 mg of propionyl-L-carnitine was orally administered, 3 times a day in addition to their usual treatment. At basal conditions and after 30, 90 and 180 days the maximum exercise time was evaluated using an exercise tolerance test performed on an ergometer bicycle and the left ventricular ejection fraction was tested by means of bidimensional echocardiography. After one month of treatment, the patients treated with propionyl-L-carnitine, compared to the control group, showed significant increases in the values of both tests, increases which became even more evident after 90 and 180 days. At the stated times the increases in the maximum exercise time were 16.4%, 22.9%, and 25.9%, respectively. The ventricular ejection fraction increased by 8.4%, 11.6% and 13.6%, respectively. On the basis of these results, having studied the particular mechanism of action of propionyl-L-carnitine the authors conclude that it represents a drug of undoubted therapeutic interest in patients with congestive heart failure, in whom it could be efficaciously administered along with a standard pharmacological therapy.


Formation and fates of nitrosamines and their formation potentials from a surface water source to drinking water treatment plants in Southern Taiwan.
Nitrosamines are toxic and emerging disinfection byproducts. In this study, three drinking water treatment plants (DWTPs) in southern Taiwan treating the same source water in Gaoping River with comparable technologies were selected. The objective was to evaluate the formation and fates of six nitrosamines and their formation potentials (FPs) from a surface water source to drinking water. Albeit decreased further downstream in the river, four nitrosamine-FPs were observed in the source water due to anthropogenic pollution in the upstream areas. In the DWTPs, nitrosamines were formed and NDMA was the main species. While high organic carbon concentrations indicated elevated nitrosamine-FPs in the source water, NDMA formation in the DWTPs was more positively associated with reductions of water parameters that quantify organic matters with double bonded ring structures. Although precursor removal via pre-oxidation is a viable approach to limit nitrosamine formation during post-disinfection, this study clearly indicates that a great portion of NDMA in treated water has been formed in the 1st oxidation step of drinking water treatment. The pre-oxidation simulations in the lab demonstrated the impact of pre-chlorination on nitrosamine formation. Given the limited removal in conventional treatment processes, avoiding nitrosamine-FPs in sources and/or nitrosamine formation during pre-oxidation become important issues to control the threats of nitrosamines in drinking water. Under current circumstance in which pre-oxidation is widely used to optimize the treatment effectiveness in many DWTPs, its adverse effect by forming nitrosamines needs to be carefully minimized and using technologies other than pre-chlorination (e.g., pre-ozonation) may be considered.


In-Vitro Comparison Of Micro-Leakage Between Nanocomposite And Microhybrid Composite In Class V Cavities Treated With The Self-Etch Technique.
When a light cure composite resin is used to restore a class V lesion, certain stresses are generated at the tooth-restoration interface. If these stresses exceed the bond strength of the restorative material, microscopic gaps are formed which eventually cause micro-leakage at the tooth-restoration interface. The objective of the present study was to compare the micro-leakage values at the tooth-restoration interface using dye penetration method between a Nano filled and a Micro hybrid light cured composite resin in class V cavities using the self-etch technique. Sixty class V cavities were made coronal to the cemento-enamel junction in the extracted premolars. These were then randomly divided into two study groups. Group A: Self-etch; filled with P-60 (microhybrid) n=30. Group B: Self-etch; filled with Z-350 (nano-filled) n=30. Specimens were subjected to thermo-cycling at 5-55 °C±2 °C with a 30 seconds dwell time. After which they were stained with 2% methylene blue. Later, sectioned bucco-lingually and examined using a stereo microscope (magnification X4) at the occlusal, axial and gingival surfaces. Micro-leakage around the toothrestoration interface was assessed by using the degree of dye penetration in millimetres. There was 100% micro leakage seen at both the occlusal and gingival surfaces when using the P-60 composite. With the Z-350 composite 84% occlusal and 88% of the gingival surfaces exhibited microleakage.. With respect to micro-leakage in class V cavities, Z-350 was found to be a superior restorative material compared to P-60 on the occlusal surface. Overall, there is no statistically significant difference in the micro-leakage exhibited by the two restorative materials in class V preparations subjected to self-etch protocol.


Role of the prostaglandin E2 receptor in mammary tumor metastasis.
Both clinical and experimental breast tumors often synthesize high levels of prostaglandins, most notably prostaglandin E2 (PGE2). We have reported previously that metastatic murine mammary tumor cells also express a high-affinity PGE2 receptor. We have now shown that the receptor plays a functional role in the metastasis of two mammary tumor cell subpopulations, lines 66 and 4526. We showed that three agents, LEO101 (LEO Pharmaceuticals), SC19220 (Searle Co.), and AH6809 (Glaxo Co.), antagonize [3H]PGE2 binding to these cells and block PGE2-mediated elevation of intracellular cyclic AMP. Pretreatment of line 66 cells with nontoxic concentrations of any of the three receptor antagonists prior to i.v. injection results in more experimental lung colonies. As shown previously, and confirmed here, pretreatment of these cells with indomethacin (which inhibits endogenous PGE synthesis and therefore increases detectable PGE receptor) inhibits metastasis. Thus, the tumor cell PGE2 receptor contributes to the ability of murine mammary tumor cells to metastasize.


Computer-assisted management of attention-deficit/hyperactivity disorder.
Medication management of attention-deficit/hyperactivity disorder (ADHD) is often suboptimal. We examined whether (1) brief physician training plus computer-assisted medication management led to greater reduction in ADHD symptoms and (2) adherence to the recommended titration protocol produced greater symptomatic improvement. A randomized medication trial was conducted that included 24 pediatric practices. Children who met criteria for ADHD were randomly assigned by practice to treatment-as-usual or a specialized care group in which physicians received 2 hours of didactic training on medication management of ADHD plus training on a software program to assist in monitoring improvement. Parent and teacher reports were obtained before treatment and 4, 9, and 12 months after starting medication. Children in both specialized care and treatment-as-usual groups improved on the ADHD Rating Scales and SNAP-IV, but there were no group differences in improvement rates. Brief physician training alone did not produce improvements. When recommended titration procedures were followed, however, outcomes were better for total and inattentive ADHD symptoms on both the ADHD Rating Scales and SNAP-IV parent and teacher scales. Results were not attributable to discontinuation because of adverse effects or failure to find an effective medication dose. Brief physician training alone did not lead to reductions in ADHD symptoms, but adherence to a protocol that involved titration until the child's symptoms were in the average range and had shown a reliable change led to better symptom reduction. Computer-assisted medication management can contribute to better treatment outcomes in primary care medication treatment of ADHD.


An oncology nurses' guide to new targeted agents for metastatic colorectal cancer.
Colorectal cancer (CRC) that has metastasized before being discovered, or reoccurs following surgery, remains a major treatment challenge. Trials have established the usefulness of antiangiogenic agents and new regimens in prolonging survival in patients with advanced disease. In the United States, the antiangiogenic agents approved for treating metastatic CRC often are combined with traditional chemotherapeutic agents and include bevacizumab (Avastin®), ziv-aflibercept (Zaltrap®), and regorafenib (Stivarga®). This article reviews factors that guide the development of a nursing plan for monitoring and managing patients who are receiving antiangiogenic therapies. Regorafenib and ziv-aflibercept, two newer agents that nurses and other healthcare professionals may have had less experience with, were reviewed. The key to maximizing the potential benefit of these agents is understanding where these new therapies fit in the overall scheme of treatment options and how to help patients tolerate treatment.


Alpha thalassaemia and the haematology of normal Jamaican children.
Haematological indices were studied from birth to 9 years in a representative sample of 195 children with a normal haemoglobin (AA) genotype subdivided according to the number of alpha globin genes. These were 5 homozygotes for alpha-thalassaemia 2 (two-gene group), 60 heterozygotes for alpha-thalassaemia 2 (three-gene group), and 130 with a normal alpha globin gene complement (four-gene group). HbF and HbA2 showed no differences between the groups. Compared to the four-gene group, the three-gene group tended to have significantly lower levels of total haemoglobin, MCHC, MCV, and MCH, and higher levels of red cell count. These differences became apparent with increasing age in the order of MCV, RBC, MCHC, and total haemoglobin. The data suggested that haematological differences were more marked in the two-gene group but with the small numbers available, the differences were not significant.


Effects of mycorrhizae on growth and demography of tallgrass prairie forbs.
The effects of arbuscular mycorrhizal (AM) symbiosis on ramet and genet densities, vegetative growth rates, and flowering of three forb species were studied in native tallgrass prairie in northeastern Kansas. Mycorrhizal activity was experimentally suppressed for six growing seasons on replicate plots in an annually burned and an infrequently burned watershed with the fungicide benomyl. Benomyl reduced mycorrhizal root colonization to an average of 4.2%, approximately a two-thirds reduction relative to controls (13.7% colonization). Mycorrhizae influenced the population structure of these forbs. Although mycorrhizal suppression had no long-term effect on genet densities and no effect on ramet survivorship throughout the growing season, the number of ramets per individual was significantly increased such that ramet densities of all three species were approximately doubled in response to long-term mycorrhizal suppression. Effects of mycorrhizae on ramet growth and reproduction varied among species. Ramet growth rates, biomass, and flowering of Salvia azurea were greater in plots with active mycorrhizal symbiosis, whereas mycorrhizae reduced ramet growth rates and biomass of Artemesia ludoviciana. Aster sericeus ramet growth rates and biomass were unaffected by the fungicide applications, but its flowering was reduced.The pattern of responses of these three species to mycorrhizae differed considerably between the two sites of contrasting fire regime, indicating that the interaction of fire-induced shifts in resource availability and mycorrhizal symbiosis together modulates plant responses and the intensity and patterns of interspecific competition between and among tallgrass prairie grass and forb species. Further, the results indicate that effects of mycorrhizae on community structure are a result of interspecific differences in the balance between direct positive effects of the symbiosis on host plant performance and indirect negative effects mediated through altered competitive interactions.


Visibility of comet nuclei.
Photography of the nucleus of comet Halley is the goal of several planned space missions. The nucleus of a comet is surrounded by a cloud of dust particles. If this cloud is optically thick, it will prevent observation of the nuclear surface. Broadband photometry of nine comets has been analyzed to determine the visibility of their nuclei. Only in the case of comet West near perihelion was the dust dense enough to interfere with imaging. Comparison of the visual brightness of the well-observed comets with that of Halley in 1910 leads to the conclusion that the nucleus of Halley can be imaged without significant obscuration by the dust.


Trends in Mortality Disparities by Area-Based Poverty in New York City, 1990-2010.
Residing in a high-poverty area has consistently been associated with higher mortality rates, but the association between poverty and mortality can change over time. We examine the association between neighborhood poverty and mortality in New York City (NYC) during 1990-2010 to document mortality disparity changes over time and determine causes of death for which disparities are greatest. We used NYC and New York state mortality data for years 1990, 2000, and 2010 to calculate all-cause and cause-specific age-adjusted death rates (AADRs) by census tract poverty (CTP), which is the proportion of persons in a census tract living below the federal poverty threshold. We calculated mortality disparities, measured as the difference in AADR between the lowest and highest CTP groups, within and across race/ethnicity, nativity, and sex categories by year. We observed higher all-cause AADRs with higher CTP for each year for all race/ethnicities, both sexes, and US-born persons. Mortality disparities decreased progressively during 1990-2010 for the NYC population overall, for each race/ethnic group, and for the majority of causes of death. The overall mortality disparity between the highest and lowest CTP groups during 2010 was 2.55 deaths/1000 population. The largest contributors to mortality disparities were heart disease (51.52 deaths/100,000 population), human immunodeficiency virus (19.96/100,000 population), and diabetes (19.59/100,000 population). We show that progress was made in narrowing socioeconomic disparities in mortality during 1990-2010, but substantial disparities remain. Future efforts toward achieving health equity in NYC mortality should focus on areas contributing most to disparities.


Healthy Aging and Sentence Production: Disrupted Lexical Access in the Context of Intact Syntactic Planning.
Healthy aging does not affect all features of language processing equally. In this study, we investigated the effects of aging on different processes involved in fluent sentence production, a complex task that requires the successful execution and coordination of multiple processes. In Experiment 1, we investigated age-related effects on the speed of syntax selection using a syntactic priming paradigm. Both young and older adults produced target sentences quicker following syntactically related primes compared to unrelated primes, indicating that syntactic facilitation effects are preserved with age. In Experiment 2, we investigated age-related effects in syntactic planning and lexical retrieval using a planning scope paradigm: participants described moving picture displays designed to elicit sentences with either initial coordinate or simple noun phrases and, on half of the trials, the second picture was previewed. Without preview, both age groups were slower to initiate sentences with larger coordinate phrases, suggesting a similar phrasal planning scope. However, age-related differences did emerge relating to the preview manipulation: while young adults displayed speed benefits of preview in both phrase conditions, older adults only displayed speed preview benefits within the initial phrase (coordinate condition). Moreover, preview outside the initial phrase (simple condition) caused older adults to become significantly more error-prone. Thus, while syntactic planning scope appears unaffected by aging, older adults do appear to encounter problems with managing the activation and integration of lexical items into syntactic structures. Taken together, our findings indicate that healthy aging disrupts the lexical, but not the syntactic, processes involved in sentence production.


Combined Pulse-Echo Ultrasound and Multispectral Optoacoustic Tomography With a Multi-Segment Detector Array.
The high complementarity of ultrasonography and optoacoustic tomography has prompted the development of combined approaches that utilize the same transducer array for detecting both optoacoustic and pulse-echo ultrasound responses from tissues. Yet, due to the fundamentally different physical contrast and image formation mechanisms, the development of detection technology optimally suited for image acquisition in both modalities remains a major challenge. Herein, we introduce a multi-segment detector array approach incorporating array segments of linear and concave geometry to optimally support both ultrasound and optoacoustic image acquisition. The various image rendering strategies are tested and optimized in numerical simulations and calibrated tissue-mimicking phantom experiments. We subsequently demonstrate real-time hybrid optoacoustic ultrasound image acquisition in a healthy volunteer. The new approach enables the acquisition of high-quality anatomical data by both modalities complemented by functional information on blood oxygenation status provided by the multispectral optoacoustic tomography.


[Evaluation of the smoking cessation course (1984-1990) of the Cancer and Lung Society of canton Zurich].
The present study is to evaluate the smoking cessation therapy of the working team of the Cancer Association and Lung Association of the State of Zurich. Roughly 1/3 of all 913 participants of the therapy from 1984 to July 1990 have responded to the survey. Of these 1/3, more than a quarter did not smoke any more one year after the therapy. An antismoking program with a 1-year smoking cessation rate of 20 to 30% is considered successful in professional circles. The smoking cessation rate of all 913 therapy participants is probably below the 27% obtained in as much as the share of the successful ones among those replying, by experience is bigger than the share of those failling. Also the more precise inquiry in the first 7 therapies of 1990 confirms these findings. There the rate of success is barely 15% after 1 to 1 1/2 year. It cannot be ascertained whether the smoking cessation rate of all therapy courses is that high or only at the time after the program restructurations at the beginning of 1990. Only a precise achievement control can guarantee a consequent and continuous therapy evaluation within the next years.


New actigraph for long-term tremor recording.
A new method of movement analysis is validated, allowing an actigraph to discriminate tremor from other movements and store duration and intensity measures of both movement types. For algorithm optimization, wrist acceleration was recorded in nine controls and nine Parkinson's disease patients, while simultaneously rating their observed tremor minute by minute on item 20 of the Unified Parkinson's Disease Rating Scale. An optimization procedure to minimize false positives in controls while maximizing tremor detection in patients resulted in false positive tremor classification in 2.4% +/- 2.5% of the movement time of control subjects (range, 0%-7%), while providing tremor classification in 82.1% +/- 15.4% of the movement time in patients (range, 55%-100%), correlating r = 0.93 with their averaged observed tremor score. A second, generalizability study showed that application of the optimized algorithm resulted in accurate classification of 71% +/- 14% of the observed tremor time (range, 46%-90%) in another 9 patients and in a false positive classification in only 0.5% +/- 0.8% of the time in another 10 controls (range, 0%-2.4%). The commercial availability of this actigraph now for the first time makes it possible to investigate tremor fluctuations over several weeks. An example is given of how long-term monitoring can be of use in evaluation of symptom management.


Invited review: A systematic review of the effects of prolonged cow-calf contact on behavior, welfare, and productivity.
Separation of calves from cows within hours or days of birth is common on dairy farms. Stakeholders have conflicting perspectives on whether this practice is harmful or beneficial for the animals' welfare and production. Our objective was to critically evaluate the scientific evidence for both acute and long-term effects of early separation versus an extended period of cow-calf contact. The outcomes investigated were the behavior, welfare (excluding physical health), and performance (milk yield and growth, respectively) of dairy cows and calves. Primary research papers were found through targeted Web of Science searches, the reference lists of recent reviews for each topic, and the reference lists of papers identified from these sources. Studies were included if they were published in English, the full text was accessible, and they compared treatments with and without contact between dairy cows and calves for a specified period. Early separation (within 24 h postpartum) was found to reduce acute distress responses of cows and calves. However, longer cow-calf contact typically had positive longer-term effects on calves, promoting more normal social behavior, reducing abnormal behavior, and sometimes reducing responses to stressors. In terms of productivity, allowing cows to nurse calves generally decreased the volume of milk available for sale during the nursing period, but we found no consistent evidence of reduced milk production over a longer period. Allowing a prolonged period of nursing increased calf weight gains during the milk-feeding period. In summary, extended cow-calf contact aggravates the acute distress responses and reduces the amount of saleable milk while the calves are suckling, but it can have positive effects on behaviors relevant to welfare in the longer term and benefit calf growth. The strength of these conclusions is limited, however, given that relatively few studies address most of these effects and that experimental design including timing of contact and observations are often inconsistent across studies. Few studies presented indicators of long-term welfare effects other than abnormal and social behavior of the calves.


Exploring the Impact of Childhood Abuse on HIV Social and Attitudinal Factors Among Adults With and Without this History in Sub-Saharan Africa: Findings from NIMH Project Accept (HPTN 043).
Using data from four sites in three African countries, this community randomized study examined the association between childhood sexual and/or physical abuse (CSA and/or CPA) and HIV disclosure, HIV-related stigma, stress, and social support among adults with and without a history of abuse. A history of abuse among men was associated with higher levels of adult-reported stress and HIV-related stigma, and with significantly lower rates of HIV test result disclosure to current partners. Women with a history of CSA and/or CPA had significantly higher perceived stigma, discrimination and stress. Although childhood abuse was significantly associated with adult stress and stigmatization, participants with histories of CSA and/or CPA also reported significantly higher perceived social support compared to people without such experiences. These findings may reflect support received in response to disclosure of CSA or CPA or emotional ambivalence in relationships that have been found to be associated with child abuse. We conclude that it is critical for HIV prevention interventions to advocate for the primary prevention of child abuse, for early identification of adolescents and adults who report experiencing childhood abuse, and to address stigma and stress-related attitudinal, behavioral and relationship difficulties experiences as an aftermath of early abuse that increase their risk of HIV.


A novel role for calcium-independent phospholipase A in alpha-amino-3-hydroxy-5-methylisoxazole-propionate receptor regulation during long-term potentiation.
A considerable body of evidence indicates that phospholipase A(2) (PLA(2)) enzymes participate in long-term potentiation (LTP) of excitatory synaptic transmission. In the present study, we have undertaken experiments to identify which calcium-independent isoform of PLA(2) is involved in synaptic plasticity and to determine whether calcium-independent PLA(2) (iPLA(2)) contributes to post-synaptic processes of LTP. Using field recordings from rat CA1 hippocampal slices, we found that theta-burst stimulation (TBS)-induced LTP of field excitatory post-synaptic potentials (fEPSPs) was abolished by the iPLA(2) inhibitor bromoenol lactone (BEL) but not by the Ca(2+)-dependent PLA(2) inhibitor arachidonyl trifluoromethyl ketone (AACOCF(3)). The ionic currents generated during TBS were not affected during iPLA(2) inhibition as BEL by itself had no effect on the magnitude of facilitation during burst responses. In addition, (R)-BEL, an enantioselective inhibitor of iPLA(2)gamma, precluded TBS-induced LTP, an action that was not replicated by the iPLA(2)beta inhibitors (S)-BEL and methyl arachidonyl fluorophosphonate. (R)-BEL was, however, ineffective on pre-established LTP. Finally, BEL also prevented the potentiation of fEPSPs elicited by brief exposure to 50 microM N-methyl-d-aspartate, as well as the associated up-regulation of alpha-amino-3-hydroxy-5-methylisoxazole-propionate (AMPA) receptor GluR1 subunit levels and the increase of (3)H-AMPA binding in crude synaptic fractions. Collectively, these results unravel a new role for iPLA(2)gamma in LTP, which appears to favor the insertion of AMPA receptors at post-synaptic membranes.


Cognition at age 70: Life course predictors and associations with brain pathologies.
To investigate predictors of performance on a range of cognitive measures including the Preclinical Alzheimer Cognitive Composite (PACC) and test for associations between cognition and dementia biomarkers in Insight 46, a substudy of the Medical Research Council National Survey of Health and Development. A total of 502 individuals born in the same week in 1946 underwent cognitive assessment at age 69-71 years, including an adapted version of the PACC and a test of nonverbal reasoning. Performance was characterized with respect to sex, childhood cognitive ability, education, and socioeconomic position (SEP). In a subsample of 406 cognitively normal participants, associations were investigated between cognition and β-amyloid (Aβ) positivity (determined from Aβ-PET imaging), whole brain volumes, white matter hyperintensity volumes (WMHV), and APOE ε4. Childhood cognitive ability was strongly associated with cognitive scores including the PACC more than 60 years later, and there were independent effects of education and SEP. Sex differences were observed on every PACC subtest. In cognitively normal participants, Aβ positivity and WMHV were independently associated with lower PACC scores, and Aβ positivity was associated with poorer nonverbal reasoning. Aβ positivity and WMHV were not associated with sex, childhood cognitive ability, education, or SEP. Normative data for 339 cognitively normal Aβ-negative participants are provided. This study adds to emerging evidence that subtle cognitive differences associated with Aβ deposition are detectable in older adults, at an age when dementia prevalence is very low. The independent associations of childhood cognitive ability, education, and SEP with cognitive performance at age 70 have implications for interpretation of cognitive data in later life.


An investigation of EEG, genetic and cognitive markers of treatment response to antidepressant medication in patients with major depressive disorder: a pilot study.
The aim of this study was to investigate if biomarkers in QEEG, genetic and neuropsychological measures are suitable for the prediction of antidepressant treatment outcome in depression. Twenty-five patients diagnosed with major depressive disorder were assessed twice, pretreatment and at 8-wk follow-up, on a variety of QEEG and neuropsychological tasks. Additionally, cheek swab samples were collected to assess genetic predictors of treatment outcome. The primary outcome measure was the absolute decrease on the HAM-D rating scale. Regression models were built in order to investigate which markers contribute most to the decrease in absolute HAM-D scores. Patients who had a better clinical outcome were characterized by a decrease in the amplitude of the Auditory Oddball N1 at baseline. The 'Met/Met' variant of the COMT gene was the best genetic predictor of treatment outcome. Impaired verbal memory performance was the best cognitive predictor. Raised frontal Theta power was the best EEG predictor of change in HAM-D scores. A tentative integrative model showed that a combination of N1 amplitude at Pz and verbal memory performance accounted for the largest part of the explained variance. These markers may serve as new biomarkers suitable for the prediction of antidepressant treatment outcome.


An experimental design approach to optimization of the liquid chromatographic separation conditions for the determination of metformin and glibenclamide in pharmaceutical formulation.
An optimization methodology is introduced for investigating the retention behavior and the separation factor of metformin, gliclazide (I.S.) and glibenclamide. This investigation has been focused on studying the influence of pH value of the mobile phase, concentration of acetonitrile and column temperature, which affect a complete separation of the chromatographic peaks of these compounds. The significant factors were optimized using full factorial design. Retention factor and separation factor were chosen as dependent variable. Optimum RP-LC chromatographic conditions for the separation of metformin, glibenclamide and gliclazide were obtained using X Terra column (150 mm × 4.6 mm I.D., 5 µm). The results show that the percentage of acetonitrile are the most important to investigate and sspH of the mobile phase and column temperature do not significantly affect the experimental results. The procedure was validated for linearity, accuracy, precision and recovery. Quantitation was accomplished using internal standard method.


Experiencing a probabilistic approach to clarify and disclose uncertainties when setting occupational exposure limits.
Assessment factors (AFs) are commonly used for deriving reference concentrations for chemicals. These factors take into account variabilities as well as uncertainties in the dataset, such as inter-species and intra-species variabilities or exposure duration extrapolation or extrapolation from the lowest-observed-adverse-effect level (LOAEL) to the noobserved- adverse-effect level (NOAEL). In a deterministic approach, the value of an AF is the result of a debate among experts and, often a conservative value is used as a default choice. A probabilistic framework to better take into account uncertainties and/or variability when setting occupational exposure limits (OELs) is presented and discussed in this paper. Each AF is considered as a random variable with a probabilistic distribution. A short literature was conducted before setting default distributions ranges and shapes for each AF commonly used. A random sampling, using Monte Carlo techniques, is then used for propagating the identified uncertainties and computing the final OEL distribution. Starting from the broad default distributions obtained, experts narrow it to its most likely range, according to the scientific knowledge available for a specific chemical. Introducing distribution rather than single deterministic values allows disclosing and clarifying variability and/or uncertainties inherent to the OEL construction process. This probabilistic approach yields quantitative insight into both the possible range and the relative likelihood of values for model outputs. It thereby provides a better support in decision-making and improves transparency. Int J Occup Med Environ Health 2018;31(4):475-489.


Genetic evidence identifying the true gluconeogenic fructose-1,6-bisphosphatase in Thermococcus kodakaraensis and other hyperthermophiles.
Fructose-1,6-bisphosphatase (FBPase) is one of the key enzymes in gluconeogenesis. Although FBPase activity has been detected in several hyperthermophiles, no orthologs corresponding to the classical FBPases from bacteria and eukaryotes have been identified in their genomes. An inositol monophosphatase (IMPase) from Methanococcus jannaschii which displayed both FBPase and IMPase activities and a structurally novel FBPase (FbpTk) from the hyperthermophilic archaeon Thermococcus kodakaraensis KOD1 have been proposed as the "missing" FBPase. For this study, using T. kodakaraensis, we took a genetic approach to elucidate which candidate is the major gluconeogenic enzyme in vivo. The IMPase/FBPase ortholog in T. kodakaraensis, ImpTk, was confirmed to possess high FBPase activity along with IMPase activity, as in the case of other orthologs. We therefore constructed Deltafbp and Deltaimp strains by applying a gene disruption system recently developed for T. kodakaraensis and investigated their phenotypes. The Deltafbp strain could not grow under gluconeogenic conditions while glycolytic growth was unimpaired, and the disruption resulted in the complete abolishment of intracellular FBPase activity. Evidently, fbpTk is an indispensable gene for gluconeogenesis and is responsible for almost all intracellular FBPase activity. In contrast, the endogenous impTk gene could not complement the defect of the fbp deletion, and its disruption did not lead to any detectable phenotypic changes under the conditions examined. These facts indicated that impTk is irrelevant to gluconeogenesis, despite the high FBPase activity of its protein product, probably due to insufficient transcription. Our results provide strong evidence that the true FBPase for gluconeogenesis in T. kodakaraensis is the FbpTk ortholog, not the IMPase/FBPase ortholog.


Smallanthus sonchifolius and Lepidium meyenii - prospective Andean crops for the prevention of chronic diseases.
Smallanthus sonchifolius (yacon) and Lepidium meyenii (maca) were the traditional crops of the original population of Peru where they are also still used in folk medicine. These plants are little known in Europe and Northern America although at least yacon can be cultivated in the climatic conditions of these regions. This article deals with the botany and the composition, the structure of main constituents, biological activity of these plants and the cultivation of yacon in the Czech Republic. The potential of yacon tubers to treat hyperglycemia, kidney problems and for skin rejuvenation and the antihyperglycemic and cytoprotective activity of its leaves seems to be related mostly to its oligofructan and phenolic content, respectively. Maca alkaloids, steroids, glucosinolates, isothicyanates and macamides are probably responsible for its aptitude to act as a fertility enhancer, aphrodisiac, adaptogen, immunostimulant, anabolic and to influence hormonal balance. Yacon and maca are already on the European market as prospective functional foods and dietary supplements, mainly for use in certain risk groups of the population, e.g. seniors, diabetics, postmenopausal women etc.


Comparative evaluation of honey, chlorhexidine gluconate (0.2%) and combination of xylitol and chlorhexidine mouthwash (0.2%) on the clinical level of dental plaque: A 30 days randomized control trial.
To compare the effect of honey, chlorhexidine mouthwash and combination of xylitol chewing gum and chlorhexidine mouthwash on the dental plaque level. Ninety healthy dental students, both male and female, aged between 21 to 25 years participated in the study. The subjects were randomly divided into three groups, i.e. the honey group, the chlorhexidine gluconate mouthwash group and the combination of xylitol chewing gum and chlorhexidine (CHX) mouthwash group. The data was collected at the baseline, 15(th) day and 30(th) day; the plaque was disclosed using disclosing solution and their scores were recorded at six sites per tooth using the Quigley and Hein plaque index modified by Turesky-Gilmore-Glickman. Statistical analysis was carried out later to compare the effect of all the three groups. P ≤ 0.05 was considered as statistically significant. Our result showed that all the three groups were effective in reducing the plaque but post-hoc LSD (Least Significant Difference) showed that honey group and chlorhexidine + xylitol group were more effective than chlorhexidine group alone. The results demonstrated a significant reduction of plaque indices in honey group and chlorhexidine + xylitol group over a period of 15 and 30 days as compared to chlorhexidine.


Are US degree-granting institutions associated with better community health determinants and outcomes?
The impact of individual education level on health outcomes is well-established, but the effect of degree-granting institutions on county health rankings (CHRs) is unknown. The objective of this study is to determine if there is an association between the presence of degree-granting institutions and CHRs. This is an ecologic study. Data for 3062 counties were derived from the Robert Wood Johnson County Health Rankings and the Integrated Postsecondary Education Data System for year 2016. Ordinal logistic regression was utilized to determine the association between presence of a degree-granting institution and county rankings for health behaviors, health outcomes, clinical care, social and economic factors, and physical environment. All models were adjusted for potential confounding factors including age, sex, race/ethnicity, English language proficiency, and urban/rural location. The presence of a degree-granting institution was positively associated with CHRs for length of life (odds ratio [OR] = 1.28; 95% confidence interval [CI]: 1.05, 1.58), health behaviors (OR = 1.46; 95% CI: 1.19, 1.79), and clinical care (OR = 1.36; 95% CI: 1.11, 1.67). Counties with the highest rankings in one health category were more likely to score in the highest rankings for other health categories. These findings suggest that degree-granting institutions are associated with CHRs. Partnerships between public health agencies and degree-granting institutions are recommended to improve population health.


Does exercise intensity affect wellness scores in a dose-like fashion?
Wellness questionnaires are common in monitoring systems, yet the sensitivity to variations in acute training intensity is unclear. This study examined the controlled dosage effects of differing exercise intensities on wellness variables and subsequent associations with neuromuscular performance. Participants (n = 10) completed low-, moderate- and high-intensity conditions of a 90 min simulated football match shuttle running protocol scaled relative to beep test scores. The protocols were completed in a randomised and counterbalanced fashion matched for time of day. Wellness (sleep quality, readiness to train, soreness, fatigue, stress, mood, motivation) and neuromuscular performance (maximal voluntary contraction, countermovement jump, 6 s cycle-ergometer sprint) were assessed pre-, post- and 24 h post-exercise. Heart rate (HR) and rating of perceived exertion (RPE) were recorded during, and session RPE (sRPE) after exercise. Generalised linear mixed models demonstrated main effects between conditions with increased HR, RPE and sRPE (P < 0.03; d > 0.8) responses from the low-high condition. Total and z-score wellness showed no significant differences between trials at any time-point (P > 0.05; d = 0.03-0.91). Fatigue was lower 24 h post-exercise for the low, compared to moderate and high conditions (P = 0.006-0.047; d = 1.20-1.77). Ratings of fatigue and soreness increased from pre- to 24 h post-trial (P < 0.003; d = 0.96-2.48), while total wellness and readiness to train decreased over time (P < 0.04; d = 0.91-1.86). Wellness showed limited capacity to differentiate training intensities. Practitioners should be aware while wellness may be highly practical, it may be limited to solely determine athlete accommodation of load considering the strength of association observed with the applied load.


Is Gram staining still useful in prosthetic joint infections?
Introduction: Staphylococcus aureus is an independent risk factor for DAIR failure in patients with a late acute prosthetic joint infection (PJI). Therefore, identifying the causative microorganism in an acute setting may help to decide if revision surgery should be chosen as a first surgical approach in patients with additional risk factors for DAIR failure. The aim of our study was to determine the sensitivity of Gram staining in late acute S. aureus PJI. Material and methods: We retrospectively evaluated all consecutive patients between 2005-2015 who were diagnosed with late acute PJI due to S. aureus. Late acute PJI was defined as the development of acute symptoms and signs of PJI, at least three months after the index surgery. Symptoms existing for more than three weeks were excluded from the analysis. Gram staining was evaluated solely for synovial fluid. Results: A total of 52 cases were included in the analysis. Gram staining was positive with Gram positive cocci in clusters in 31 cases (59.6%). Patients with a C-reactive protein (CRP) > 150 mg/L at clinical presentation had a significantly higher rate of a positive Gram stain (30/39, 77%) compared to patients with a CRP ≤ 150 mg/L (4/10, 40%) (p=0.02). A positive Gram stain was not related to a higher failure rate (60.6% versus 57.9%, p 0.85). Conclusion: Gram staining may be a useful diagnostic tool in late acute PJI to identify S. aureus PJI. Whether a positive Gram stain should lead to revision surgery instead of DAIR should be determined per individual case.


Technology-facilitated depression care management among predominantly Latino diabetes patients within a public safety net care system: comparative effectiveness trial design.
Health disparities in minority populations are well recognized. Hispanics and Latinos constitute the largest ethnic minority group in the United States; a significant proportion receives their care via a safety net. The prevalence of diabetes mellitus and comorbid depression is high among this group, but the uptake of evidence-based collaborative depression care management has been suboptimal. The study design and baseline characteristics of the enrolled sample in the Diabetes-Depression Care-management Adoption Trial (DCAT) establishes a quasi-experimental comparative effectiveness research clinical trial aimed at accelerating the adoption of collaborative depression care in safety net clinics. The study was conducted in collaboration with the Los Angeles County Department of Health Services at eight county-operated clinics. DCAT has enrolled 1406 low-income, predominantly Hispanic/Latino patients with diabetes to test a translational model of depression care management. This three-group study compares usual care with a collaborative care team support model and a technology-facilitated depression care model that provides automated telephonic depression screening and monitoring tailored to patient conditions and preferences. Call results are integrated into a diabetes disease management registry that delivers provider notifications, generates tasks, and issues critical alerts. All subjects receive comprehensive assessments at baseline, 6, 12, and 18 months by independent English-Spanish bilingual interviewers. Study outcomes include depression outcomes, treatment adherence, satisfaction, acceptance of assessment and monitoring technology, social and economic stress reduction, diabetes self-care management, health care utilization, and care management model cost and cost-effectiveness comparisons. DCAT's goal is to optimize depression screening, treatment, follow-up, outcomes, and cost savings to reduce health disparities.


Deformation-induced bandgap tuning of 2D silicon-based photonic crystals.
We address the issue of tuning the absolute bandgap in 2D silicon-based photonic crystals by mechanical deformation. The moving least-square (MLS) method, recently proposed by the authors for photonic bandgap materials, is employed for the real-space computation of band structures. The uniaxial tension mode is shown to be more effective for bandgap tuning than both pure and simple shear deformations. We verify that bandgap modifications are strongly influenced by the deformation-induced distortion of interfaces between inclusions and matrix. This result ensures the usefulness of real-space technique for the accurate calculation of strained photonic bandgap materials.


An autocatalytic cycle in autoxidation of triethylborane.
An autocatalytic cycle was found in the mechanism of autoxidation of triethylborane using density functional theory calculations. The reaction starts with the generation of an ethyl radical via slow homolytic substitution. Fast radical propagation then takes place through a catalytic cycle in which the ethyl radical acts as a catalyst.


A conceptual model of barriers and facilitators to primary clinical teams requesting pediatric palliative care consultation based upon a narrative review.
Despite evidence that referral to pediatric palliative care reduces suffering and improves quality of life for patients and families, many clinicians delay referral until the end of life. The purpose of this article is to provide a conceptual model for why clinical teams delay discussing palliative care with parents. Building on a prior model of parent regoaling and relevant research literature, we argue for a conceptual model of the challenges and facilitators a clinical team might face in shifting from a restorative-focused treatment plan to a plan that includes palliative aspects, resulting in a subspecialty palliative care referral. Like patients and families, clinicians and clinical teams may recognize that a seriously ill patient would benefit from palliative care and shift from a restorative mindset to a palliative approach. We call this transition "clinician regoaling". Clinicians may experience inhibitors and facilitators to this transition at both the individual and team level which influence the clinicians' willingness to consult subspecialty palliative care. The 8 inhibitors to team level regoaling include: 1) team challenges due to hierarchy, 2) avoidance of criticizing colleagues, 3) structural communication challenges, 4) group norms in favor of restorative goals, 5) diffusion of responsibility, 6) inhibited expression of sorrow, 7) lack of social support, 8) reinforcement of labeling and conflict. The 6 facilitators of team regoaling include: 1) processes to build a shared mental model, 2) mutual trust to encourage dissent, 3) anticipating conflict and team problem solving, 4) processes for reevaluation of goals, 5) sharing serious news as a team, 6) team flexibility. Recognizing potential team level inhibitors to transitioning to palliative care can help clinicians develop strategies for making the transition more effectively when appropriate.


E2Fs regulate adipocyte differentiation.
When preadipocytes reenter the cell cycle, PPAR gamma expression is induced, coincident with an increase in DNA synthesis, suggesting the involvement of the E2F family of cell cycle regulators. We show here that E2F1 induces PPAR gamma transcription during clonal expansion, whereas E2F4 represses PPARg amma expression during terminal adipocyte differentiation. Using a combination of in vivo experiments with knockout and chimeric animals and in vitro experiments, we demonstrate that the absence of E2F1 impairs, whereas depletion of E2F4 stimulates, adipogenesis. E2Fs hence represent the link between proliferative signaling pathways, triggering clonal expansion, and terminal adipocyte differentiation through regulation of PPAR gamma expression. This underscores the complex role of the E2F protein family in the control of both cell proliferation and differentiation.


Current selection for lower migratory activity will drive the evolution of residency in a migratory bird population.
Global warming is impacting biodiversity by altering the distribution, abundance, and phenology of a wide range of animal and plant species. One of the best documented responses to recent climate change is alterations in the migratory behavior of birds, but the mechanisms underlying these phenotypic adjustments are largely unknown. This knowledge is still crucial to predict whether populations of migratory birds will adapt to a rapid increase in temperature. We monitored migratory behavior in a population of blackcaps (Sylvia atricapilla) to test for evolutionary responses to recent climate change. Using a common garden experiment in time and captive breeding we demonstrated a genetic reduction in migratory activity and evolutionary change in phenotypic plasticity of migration onset. An artificial selection experiment further revealed that residency will rapidly evolve in completely migratory bird populations if selection for shorter migration distance persists. Our findings suggest that current alterations of the environment are favoring birds wintering closer to the breeding grounds and that populations of migratory birds have strongly responded to these changes in selection. The reduction of migratory activity is probably an important evolutionary process in the adaptation of migratory birds to climate change, because it reduces migration costs and facilitates the rapid adjustment to the shifts in the timing of food availability during reproduction.


Global health training and postgraduate medical education in Australia: the case for greater integration.
Global health (GH) training is well established overseas (particularly in North America) and reflects an increasing focus on social accountability in medical education. Despite significant interest among trainees, GH is poorly integrated with specialty training programs in Australia. While there are numerous benefits from international rotations in resource-poor settings, there are also risks to the host community, trainee and training provider. Safe and effective placements rely on firm ethical foundations as well as strong and durable partnerships between Australian and overseas health services, educational institutions and GH agencies. More formal systems of GH training in Australia have the potential to produce fellows with the skills and knowledge necessary to engage in regional health challenges in a global context.


The therapeutic use of isometamidium chloride against Cryptobia salmositica in rainbow trout Oncorhynchus mykiss.
Rainbow trout Oncorhynchus mykiss injected intramuscularly with isometamidium chloride (0.01 or 0.1 mg kg-1) at 3 wk post-infection and given a booster 2 wk later had significantly lower parasitaemias than infected controls. Packed cell volume increased after treatment and remained higher than in infected controls. The concentration of isometamidium in plasma was highest at 2 wk after injection and then declined. An intramuscular dose of 1.0 mg kg-1 of isometamidium chloride at 1, 2 and 3 wk postinfection (preclinical) significantly reduced the parasitaemia in rainbow trout 2 wk after treatment. A booster at 9 wk postinfection (chronic disease phase) reduced the parasitaemia further in all fish. The packed cell volume in these fish was higher than in infected controls. Treatment at 5, 6, and 7 wk postinfection (acute disease) had no effects and parasitaemias in treated fish were higher than in infected controls; also, anti-Cryptobia salmositica antibodies and titres of complement-fixing antibody were higher in these than in infected controls. Incubation of immune plasma or complement with isometamidium for 3 h did not affect the lytic titres of complement-fixing antibodies nor rainbow trout complement.


How do adolescents regulate distress according to attachment style? A combined eye-tracking and neurophysiological approach.
According to attachment theory, attachment representations influence emotion regulation (ER) across the lifespan. However, research into attachment-related ER in adolescence is still scarce. The aim of this study was to assess attachment-related ER using a multimodal approach, relying on behavioral and neurophysiological parameters. Attachment styles in eighty-one adolescents were assessed with the Attachment Style Interview (ASI). A distress-then-comfort paradigm based on visual stimuli (the Besancon Affective Picture Set-Adolescents) was employed to "activate" then "deactivate" the attachment system. Gaze and neurophysiological parameters of ER strategies were assessed using eye-tracking synchronized with a physiological device. During the first phase "distress exposure", attachment style was associated with the early stage of distress processing indexed by first fixation duration. Withdrawn adolescents fixated distress pictures less than other groups. Fearful adolescents showed a longer first fixation duration than withdrawn adolescents. During the following phase, "comfort-seeking", all groups initially fixed joy-complicity and comfort pictures earlier than neutral pictures, except for withdrawn adolescents, who fixated comfort pictures later than neutral pictures. Additionally, withdrawn adolescents explored comfort pictures less than enmeshed adolescents. Enmeshed adolescents explored neutral pictures less than comfort and joy-complicity pictures. Concerning neurophysiological parameters, first fixation duration correlated positively with Skin Conductance Response (SCR) rise time in fearful adolescents, while glance count correlated negatively with SCR latency in withdrawn adolescents. This study provides an innovative and objective evaluation of behavioral and neurophysiological parameters for attachment-related ER in adolescents, with a temporal resolution. These parameters constitute potential biomarkers that could contribute to our understanding of ER differences in insecure adolescents. This study was registered with the clinical trials database ClinicalTrials.gov on August 01, 2016, under the number NCT02851810.


Laparoscopic cholecystectomy for acute cholecystitis in the elderly: is it safe?
The purpose of this study was to evaluate the outcome of laparoscopic cholecystectomy (LC) in patients with acute cholecystitis aged 75 years and older. A retrospective chart review was performed on the 1216 cholecystectomies performed in our department from 2000 to 2005. A total of 225 patients underwent attempted LC for acute cholecystitis, of whom 42 were more than 75 years old and 183 younger. There was no difference in mean duration of symptoms before admission and length of hospital stay before surgery (3.8 d in elderly vs. 3.1 in younger patients, and 2.8 vs. 2.3 d, respectively). In all, 21% of the elderly patients had American Society of Anesthesiologists score III and IV. Mean operative time and conversion rate to open surgery were similar in both groups. Postoperative stay was longer in elderly (3.9 vs. 2.8). The postoperative complications rate and mortality were significantly higher in the elderly group (31% vs. 15%, and 4.8% vs. 0.5%, respectively). LC in elderly patients suffering from acute cholecystitis is feasible and effective. It is associated with a higher rate of morbidity unrelated to the surgical site and mortality in elderly compared with younger patients. Stronger selection of elderly patients for surgery is needed.


Symptom assessment in palliative care: a need for international collaboration.
This article describes the research strategy for the development of a computerized assessment tool as part of a European Union (EU)-funded project, the European Palliative Care Research Collaborative (EPCRC). The EPCRC is funded through the Sixth Framework Program of the EU with major objectives to develop a computer-based assessment and classification tool for pain, depression, and cachexia. A systematic approach will be applied for the tool development with emphasis on multicultural and multilanguage challenges across Europe. The EPCRC is based on a long lasting collaboration within the European Association for Palliative Care Research Network. The ongoing change in society towards greatly increased use of communication as well as information transfer via digital systems will rapidly change the health care system. Therefore, patient-centered outcome assessment tools applicable for both clinic and research should be developed. Report of symptoms via digital media provides a start for face-to-face communication, treatment decisions, and assessment of treatment effects. The increased use of electronic media for exchange of information may facilitate the development and use of electronic assessment tools and decision-making systems in oncology. In the future, patients may find that a combination of a face-to-face interview plus a transfer of information of subjective symptoms by electronic means will optimize treatment.


DNA topoisomerase I as one of the cellular targets of certain tyrphostin derivatives.
DNA topoisomerases (topo) are the cellular targets of several anticancer drugs used today in the clinic. Our previous work demonstrated that certain tyrphostin derivatives, known as protein tyrosine kinase antagonists, are catalytic inhibitors of DNA topoisomerases I (topo I) in vitro. In this study, we examined the ability of tyrphostin derivatives to affect the activity of topo I in the cell (in vivo) and determined their in vivo mode of action. Two approaches were used; in the first, we examined the direct effect of the treatment of tumor cells with tyrphostins on the activity, level, and post-translational modifications of the cellular topo I. The second approach was to determine the influence of pretreatment of tumor cells with tyrphostin on the cellular induced effects of camptothecin (CPT), a known inhibitor of topo I. The results show that treatment of fibrosarcoma cells with tyrphostin inhibited the DNA relaxation activity of topo I but did not reduce the level of topo I protein. Tyrphostin treatments caused conformational changes of the cellular topo I probably by binding to the enzyme. Pretreatment of the cells with tyrphostin before CPT prevented the CPT-induced degradation of topo I and reduced the enzyme-DNA cleavable complexes and the ubiquitination/sumoylation of the enzyme. These data suggest that topo I is one of the cellular targets of tyrphostin and that this drug acts in vivo (in the cell) as a catalytic inhibitor of the enzyme that alters the binding of the enzyme to the DNA.


Kinematics fingerprints of leader and follower role-taking during cooperative joint actions.
Performing online complementary motor adjustments is quintessential to joint actions since it allows interacting people to coordinate efficiently and achieve a common goal. We sought to determine whether, during dyadic interactions, signaling strategies and simulative processes are differentially implemented on the basis of the interactional role played by each partner. To this aim, we recorded the kinematics of the right hand of pairs of individuals who were asked to grasp as synchronously as possible a bottle-shaped object according to an imitative or complementary action schedule. Task requirements implied an asymmetric role assignment so that participants performed the task acting either as (1) Leader (i.e., receiving auditory information regarding the goal of the task with indications about where to grasp the object) or (2) Follower (i.e., receiving instructions to coordinate their movements with their partner's by performing imitative or complementary actions). Results showed that, when acting as Leader, participants used signaling strategies to enhance the predictability of their movements. In particular, they selectively emphasized kinematic parameters and reduced movement variability to provide the partner with implicit cues regarding the action to be jointly performed. Thus, Leaders make their movements more "communicative" even when not explicitly instructed to do so. Moreover, only when acting in the role of Follower did participants tend to imitate the Leader, even in complementary actions where imitation is detrimental to joint performance. Our results show that mimicking and signaling are implemented in joint actions according to the interactional role of the agent, which in turn is reflected in the kinematics of each partner.


A deletion in the STA1 promoter determines maltotriose and starch utilization in STA1+ Saccharomyces cerevisiae strains.
Diastatic strains of Saccharomyces cerevisiae are common contaminants in beer fermentations and are capable of producing an extracellular STA1-encoded glucoamylase. Recent studies have revealed variable diastatic ability in strains tested positive for STA1, and here, we elucidate genetic determinants behind this variation. We show that poorly diastatic strains have a 1162-bp deletion in the promoter of STA1. With CRISPR/Cas9-aided reverse engineering, we show that this deletion greatly decreases the ability to grow in beer and consume dextrin, and the expression of STA1. New PCR primers were designed for differentiation of highly and poorly diastatic strains based on the presence of the deletion in the STA1 promoter. In addition, using publically available whole genome sequence data, we show that the STA1 gene is prevalent among the 'Beer 2'/'Mosaic Beer' brewing strains. These strains utilize maltotriose efficiently, but the mechanisms for this have been unknown. By deleting STA1 from a number of highly diastatic strains, we show here that extracellular hydrolysis of maltotriose through STA1 appears to be the dominant mechanism enabling maltotriose use during wort fermentation in STA1+ strains. The formation and retention of STA1 seems to be an alternative evolutionary strategy for efficient utilization of sugars present in brewer's wort. The results of this study allow for the improved reliability of molecular detection methods for diastatic contaminants in beer and can be exploited for strain development where maltotriose use is desired.


The PGI enzyme system and fitness response to temperature as a measure of environmental tolerance in an invasive species.
In the field of invasion ecology, the determination of a species' environmental tolerance, is a key parameter in the prediction of its potential distribution, particularly in the context of global warming. In poikilothermic species such as insects, temperature is often considered the most important abiotic factor that affects numerous life-history and fitness traits through its effect on metabolic rate. Therefore the response of an insect to challenging temperatures may provide key information as to its climatic and therefore spatial distribution. Variation in the phosphoglucose-6-isomerase (PGI) metabolic enzyme-system has been proposed in some insects to underlie their relative fitness, and is recognised as a key enzyme in their thermal adaptation. However, in this context it has not been considered as a potential mechanism contributing to a species invasive cability. The present study aimed to compare the thermal tolerance of an invasive scarabaeid beetle, Costelytra zealandica (White) with that of the closely related, and in part sympatrically occurring, congeneric non-invasive species C. brunneum (Broun), and to consider whether any correlation with particular PGI genotypes was apparent. Third instar larvae of each species were exposed to one of three different temperatures (10, 15 and 20 °C) over six weeks and their fitness (survival and growth rate) measured and PGI phenotyping performed via cellulose acetate electrophoresis. No consistent relationship between PGI genotypes and fitness was detected, suggesting that PGI may not be contributing to the invasion success and pest status of C. zealandica.


Response of Escherichia coli to Prolonged Berberine Exposure.
Berberine is a plant-derived alkaloid possessing antimicrobial activity; unfortunately, its efflux through multidrug resistance pumps reduces its efficacy. Cellular life span of Escherichia coli is generally shorter with prolonged berberine exposure; nevertheless, about 30% of the cells still remain robust following this treatment. To elucidate its mechanism of action and to identify proteins that could be involved in development of antimicrobial resistance, protein profiles of E. coli cells treated with berberine for 4.5 and 8 hours were compared with control cells. A total of 42 proteins were differentially expressed in cells treated with berberine for 8 hours when compared to control cells. In both 4.5 and 8 hours of berberine-treated cells, carbohydrate and peptide uptake regimens remained unchanged, although amino acid maintenance regimen switched from transport to synthesis. Defect in cell division persisted and this condition was confirmed by images obtained from scanning electron microscopy. Universal stress proteins were not involved in stress response. The significant increase in the abundance of elongation factors could suggest the involvement of these proteins in protection by exhibiting chaperone activities. Furthermore, the involvement of the outer membrane protein OmpW could receive special attention as a protein involved in response to antimicrobial agents, since the expression of only this porin protein was upregulated after 8 hours of exposure.


Structure and Mechanism of Acetylation by the N-Terminal Dual Enzyme NatA/Naa50 Complex.
NatA co-translationally acetylates the N termini of over 40% of eukaryotic proteins and can associate with another catalytic subunit, Naa50, to form a ternary NatA/Naa50 dual enzyme complex (also called NatE). The molecular basis of association between Naa50 and NatA and the mechanism for how their association affects their catalytic activities in yeast and human are poorly understood. Here, we determined the X-ray crystal structure of yeast NatA/Naa50 as a scaffold to understand coregulation of NatA/Naa50 activity in both yeast and human. We find that Naa50 makes evolutionarily conserved contacts to both the Naa10 and Naa15 subunits of NatA. These interactions promote catalytic crosstalk within the human complex, but do so to a lesser extent in the yeast complex, where Naa50 activity is compromised. These studies have implications for understanding the role of the NatA/Naa50 complex in modulating the majority of the N-terminal acetylome in diverse species.


Vitamin D and calcium intake and risk of early menopause.
Background: Early menopause, defined as the cessation of ovarian function before the age of 45 y, affects ∼10% of women and is associated with higher risk of cardiovascular disease, osteoporosis, and other conditions. Few modifiable risk factors for early menopause have been identified, but emerging data suggest that high vitamin D intake may reduce risk.Objective: We evaluated how intakes of vitamin D and calcium are associated with the incidence of early menopause in the prospective Nurses' Health Study II (NHS2).Design: Intakes of vitamin D and calcium from foods and supplements were measured every 4 y with the use of a food-frequency questionnaire. Cases of incident early menopause were identified from all participants who were premenopausal at baseline in 1991; over 1.13 million person-years, 2041 women reported having natural menopause before the age of 45 y. We used Cox proportional hazards regression to evaluate relations between intakes of vitamin D and calcium and incident early menopause while accounting for potential confounding factors.Results: After adjustment for age, smoking, and other factors, women with the highest intake of dietary vitamin D (quintile median: 528 IU/d) had a significant 17% lower risk of early menopause than women with the lowest intake [quintile median: 148 IU/d; HR: 0.83 (95% CI: 0.72, 0.95); P-trend = 0.03]. Dietary calcium intake in the highest quintile (median: 1246 mg/d) compared with the lowest (median: 556 mg/d) was associated with a borderline significantly lower risk of early menopause (HR: 0.87; 95% CI: 0.76, 1.00; P-trend = 0.03). Associations were stronger for vitamin D and calcium from dairy sources than from nondairy dietary sources, whereas high supplement use was not associated with lower risk.Conclusions: Findings suggest that high intakes of dietary vitamin D and calcium may be modestly associated with a lower risk of early menopause. Further studies evaluating 25-hydroxyvitamin D concentrations, other dairy constituents, and early menopause are warranted.


Control of pyrethroid-resistant Anopheles gambiae and Culex quinquefasciatus mosquitoes with chlorfenapyr in Benin.
To compare the efficacy of chlorfenapyr applied on mosquito nets and as an indoor residual spray against populations of Anopheles gambiae and Culex quinquefasciatus in an area of Benin that shows problematic levels of pyrethroid resistance. Eight-week trial conducted in experimental huts. Indoor residual spraying killed 82.9% of An. gambiae overall (mean mortality: 79.5%) compared to 53.5% overall (mean mortality: 61.7%) in the hut containing the lower dosed ITN. Analysis of data on a fortnightly basis showed high levels of mosquito mortality and blood-feeding inhibition during the first few weeks after treatment. Control of C. quinquefasciatus by the IRS and ITN interventions showed a similar trend to that of An. gambiae and though the average level of mortality was lower it was still much higher than with pyrethroid treatments against this population. Chlorfenapyr's reputation for being rather slow acting was evident particularly at lower dosages. The treatments showed no evidence of excito-repellent activity in this trial. Chlorfenapyr has the potential to control pyrethroid resistant populations of A. gambiae. There is a need to develop long-lasting formulations of chlorfenapyr to prolong its residual life on nets and sprayed surfaces. On nets it could be combined with a contact irritant pyrethroid to give improved protection against mosquito biting while killing pyrethroid-resistant mosquitoes that come into contact with the net.


Synergistic effects of climate and land-use change influence broad-scale avian population declines.
Climate and land-use changes are expected to be the primary drivers of future global biodiversity loss. Although theory suggests that these factors impact species synergistically, past studies have either focused on only one in isolation or have substituted space for time, which often results in confounding between drivers. Tests of synergistic effects require congruent time series on animal populations, climate change and land-use change replicated across landscapes that span the gradient of correlations between the drivers of change. Using a unique time series of high-resolution climate (measured as temperature and precipitation) and land-use change (measured as forest change) data, we show that these drivers of global change act synergistically to influence forest bird population declines over 29 years in the Pacific Northwest of the United States. Nearly half of the species examined had declined over this time. Populations declined most in response to loss of early seral and mature forest, with responses to loss of early seral forest amplified in landscapes that had warmed over time. In addition, birds declined more in response to loss of mature forest in areas that had dried over time. Climate change did not appear to impact populations in landscapes with limited habitat loss, except when those landscapes were initially warmer than the average landscape. Our results provide some of the first empirical evidence of synergistic effects of climate and land-use change on animal population dynamics, suggesting accelerated loss of biodiversity in areas under pressure from multiple global change drivers. Furthermore, our findings suggest strong spatial variability in the impacts of climate change and highlight the need for future studies to evaluate multiple drivers simultaneously to avoid potential misattribution of effects.


Assessment of Electrolyte Replacement in Critically Ill Patients During a Drug Shortage.
Purpose: The purpose of this study was to determine if national drug shortages of electrolyte replacement products negatively impact patient care. Methods: This study was a single-center, retrospective, observational cohort of adults admitted to the medical, surgical, or trauma intensive care unit (ICU) that were ordered or would have qualified for the general or continuous renal replacement therapy electrolyte replacement protocol (ERP) between April 2017 and August 2018. In October 2017, ERP use was suspended and enteral replacement was promoted due to inability to maintain consistent inventory of intravenous replacement products. The primary objective was to compare the percentage of patient days that at least 1 critically low value of potassium, magnesium, and/or phosphorus existed between protocolized and nonprotocolized electrolyte replacement. Secondary objectives included characterizing the ratio of enteral replacement to duration of critically low electrolyte values during protocolized and nonprotocolized electrolyte replacement. Results: A total of 288 patients were included. The mean percentage of ICU days with low electrolyte levels in the protocolized period was significantly higher than in the nonprotocolized period (21.4% vs 17.5%, P = .0238). There was a negative relationship between the total electrolyte replacement that was given enterally and the percentage of patient days with critically low values indicating that as enteral replacement increased, percentage of days with low values decreased. The association between percentage of enteral replacement and days with critically low electrolyte values was significantly lower in the protocolized period. Conclusion: Intravenous electrolyte replacement product shortages did not result in an increased incidence of critically low electrolyte values. Enteral replacement was associated with a decreased incidence of low electrolyte values.


Structural reinforcement of microvascular networks using electrostatic layer-by-layer assembly with halloysite nanotubes.
We demonstrate a method for tailoring local mechanical properties near channel surfaces of vascular structural polymers in order to achieve high structural performance in microvascular systems. While synthetic vascularized materials have been created by a variety of manufacturing techniques, unreinforced microchannels act as stress concentrators and lead to the initiation of premature failure. Taking inspiration from biological tissues such as dentin and bone, these mechanical deficiencies can be mitigated by complex hierarchical structural features near to channel surfaces. By employing electrostatic layer-by-layer assembly (ELbL) to deposit films containing halloysite nanotubes onto scaffold surfaces followed by matrix infiltration and scaffold removal, we are able to controllably deposit nanoscale reinforcement onto 200 micron diameter channel surface interiors in microvascular networks. High resolution strain measurements on reinforced networks under load verify that the halloysite reduces strain concentrations and improves mechanical performance.


Particle size distributions by transmission electron microscopy: an interlaboratory comparison case study.
This paper reports an interlaboratory comparison that evaluated a protocol for measuring and analysing the particle size distribution of discrete, metallic, spheroidal nanoparticles using transmission electron microscopy (TEM). The study was focused on automated image capture and automated particle analysis. NIST RM8012 gold nanoparticles (30 nm nominal diameter) were measured for area-equivalent diameter distributions by eight laboratories. Statistical analysis was used to (1) assess the data quality without using size distribution reference models, (2) determine reference model parameters for different size distribution reference models and non-linear regression fitting methods and (3) assess the measurement uncertainty of a size distribution parameter by using its coefficient of variation. The interlaboratory area-equivalent diameter mean, 27.6 nm ± 2.4 nm (computed based on a normal distribution), was quite similar to the area-equivalent diameter, 27.6 nm, assigned to NIST RM8012. The lognormal reference model was the preferred choice for these particle size distributions as, for all laboratories, its parameters had lower relative standard errors (RSEs) than the other size distribution reference models tested (normal, Weibull and Rosin-Rammler-Bennett). The RSEs for the fitted standard deviations were two orders of magnitude higher than those for the fitted means, suggesting that most of the parameter estimate errors were associated with estimating the breadth of the distributions. The coefficients of variation for the interlaboratory statistics also confirmed the lognormal reference model as the preferred choice. From quasi-linear plots, the typical range for good fits between the model and cumulative number-based distributions was 1.9 fitted standard deviations less than the mean to 2.3 fitted standard deviations above the mean. Automated image capture, automated particle analysis and statistical evaluation of the data and fitting coefficients provide a framework for assessing nanoparticle size distributions using TEM for image acquisition.


Conflicting Selection Pressures Will Constrain Viral Escape from Interfering Particles: Principles for Designing Resistance-Proof Antivirals.
The rapid evolution of RNA-encoded viruses such as HIV presents a major barrier to infectious disease control using conventional pharmaceuticals and vaccines. Previously, it was proposed that defective interfering particles could be developed to indefinitely control the HIV/AIDS pandemic; in individual patients, these engineered molecular parasites were further predicted to be refractory to HIV's mutational escape (i.e., be 'resistance-proof'). However, an outstanding question has been whether these engineered interfering particles-termed Therapeutic Interfering Particles (TIPs)-would remain resistance-proof at the population-scale, where TIP-resistant HIV mutants may transmit more efficiently by reaching higher viral loads in the TIP-treated subpopulation. Here, we develop a multi-scale model to test whether TIPs will maintain indefinite control of HIV at the population-scale, as HIV ('unilaterally') evolves toward TIP resistance by limiting the production of viral proteins available for TIPs to parasitize. Model results capture the existence of two intrinsic evolutionary tradeoffs that collectively prevent the spread of TIP-resistant HIV mutants in a population. First, despite their increased transmission rates in TIP-treated sub-populations, unilateral TIP-resistant mutants are shown to have reduced transmission rates in TIP-untreated sub-populations. Second, these TIP-resistant mutants are shown to have reduced growth rates (i.e., replicative fitness) in both TIP-treated and TIP-untreated individuals. As a result of these tradeoffs, the model finds that TIP-susceptible HIV strains continually outcompete TIP-resistant HIV mutants at both patient and population scales when TIPs are engineered to express >3-fold more genomic RNA than HIV expresses. Thus, the results provide design constraints for engineering population-scale therapies that may be refractory to the acquisition of antiviral resistance.


Using 'may contain' labelling to inform food choice: a qualitative study of nut allergic consumers.
Precautionary 'may contain' warnings are used to indicate possible allergen contamination. Neither food safety nor foods labelling legislation address this issue. The aim of this study is to understand how peanut and nut allergic adults interpret 'may contain' labelling and how they use this information when purchasing food. Qualitative methods were used to explore both behaviour and attitudes. The behaviour and 'thinking aloud' of 32 participants were recorded during their normal food shop. A semi-structured interview also explored participants' views about 13 potentially problematic packaged foods. Transcribed data from these tasks were analysed to explore the interpretation of 'may contain' labelling and how this influenced food choice decisions. Peanut and nut allergic individuals adopt a complex range of responses and strategies to interpret 'may contain' labelling. Many claimed such labelling was not credible or desirable; many ignored it whilst some found it helpful and avoided products with all such labelling. Interpretation and consequent decisions were not only based on the detail of the labelling but also on external factors such as the nature of the product, the perceived trustworthiness of the producer and on the previous experience of the nut allergic individual. 'May contain' labelling was interpreted in the light of judgements about the product, producer and previous personal experience. It is vital that these interpretation strategies are taken into account by those responsible for labelling itself and for the provision of advice to nut allergic individuals. Suggestions to improve labelling and advice to the allergic individual are considered.


Timing of Antidepressant Discontinuation During Pregnancy and Postpartum Psychiatric Outcomes in Denmark and Norway.
Approximately one-half of women treated for affective disorders discontinue antidepressant use during pregnancy, yet this discontinuation could lead to relapse post partum. To investigate the associations between longitudinal antidepressant fill trajectories during pregnancy and postpartum psychiatric outcomes. This cohort study used nationwide registers in Denmark and Norway. The sample included 41 475 live-born singleton pregnancies in Denmark (1997-2016) and 16 459 in Norway (2009-2018) for women who filled at least 1 antidepressant prescription within 6 months before pregnancy. Antidepressant prescription fills were obtained from the prescription registers. Antidepressant treatment during pregnancy was modeled using the k-means longitudinal method. Initiation of psycholeptics, psychiatric emergencies, or records of self-harm within 1 year post partum. Between April 1 and October 30, 2022, hazard ratios (HRs) for each psychiatric outcome were estimated using Cox proportional hazards regression models. Inverse probability of treatment weighting was used to control for confounding. Country-specific HRs were pooled using random-effects meta-analytic models. Among 57 934 pregnancies (mean [SD] maternal age, 30.7 [5.3] years in Denmark and 29.9 [5.5] years in Norway), 4 antidepressant fill trajectories were identified: early discontinuers (31.3% and 30.4% of the included pregnancies in Denmark and Norway, respectively), late discontinuers (previously stable users) (21.5% and 27.8%), late discontinuers (short-term users) (15.9% and 18.4%), and continuers (31.3% and 23.4%). Early discontinuers and late discontinuers (short-term users) had a lower probability of initiating psycholeptics and having postpartum psychiatric emergencies vs continuers. A moderately increased probability of initiation of psycholeptics was found among late discontinuers (previously stable users) vs continuers (HR, 1.13; 95% CI, 1.03-1.24). This increase in late discontinuers (previously stable users) was more pronounced among women with previous affective disorders (HR, 1.28; 95% CI, 1.12-1.46). No association between antidepressant fill trajectories and postpartum self-harm risk was found. Based on pooled data from Denmark and Norway, a moderately elevated probability of initiation of psycholeptics in late discontinuers (previously stable users) vs continuers was found. These findings suggest that women with severe mental illness who are currently on stable treatment may benefit from continuing antidepressant treatment and personalized treatment counseling during pregnancy.


The psychological risks of Vietnam for U.S. veterans: a revisit with new data and methods.
In 1988, the National Vietnam Veterans Readjustment Study (NVVRS) of a representative sample of 1200 veterans estimated that 30.9% had developed posttraumatic stress disorder (PTSD) during their lifetimes and that 15.2% were currently suffering from PTSD. The study also found a strong dose-response relationship: As retrospective reports of combat exposure increased, PTSD occurrence increased. Skeptics have argued that these results are inflated by recall bias and other flaws. We used military records to construct a new exposure measure and to cross-check exposure reports in diagnoses of 260 NVVRS veterans. We found little evidence of falsification, an even stronger dose-response relationship, and psychological costs that were lower than previously estimated but still substantial. According to our fully adjusted PTSD rates, 18.7% of the veterans had developed war-related PTSD during their lifetimes and 9.1% were currently suffering from PTSD 11 to 12 years after the war; current PTSD was typically associated with moderate impairment.