Interpreting archaeological site-formation processes at a mountain ice patch: A case study from Langfonne, Norway

In the context of global warming, ice patches are increasingly important foci of high-elevation archaeology. Langfonne in Jotunheimen, central southern Norway, is uniquely suited to provide a window onto site formation processes and taphonomy in this novel archaeological setting. Here the site record from systematic survey includes the largest number of arrows, bones and antlers from a single ice patch worldwide. Combining data from these finds with the results of glaciological investigations provides an opportunity to interpret the influence of archaeological site formation processes and taphonomy on chronological and spatial patterning. It is inferred that the spatial patterning of artefacts at Langfonne is partly a result of displacement by ice movement, meltwater and other natural processes. Nevertheless, the finds yield information regarding past hunting practices and the extent of ice at different times. An early cluster of finds from c.6000 cal yr BP may result from ice deformation which has brought early objects to the surface. The number of arrows increases from c. 1700 cal yr BP onwards, peaking around c.1200 cal yr BP. Artefacts from this period show a wide spatial distribution indicating both the preferential survival of more recent finds and that they were lost when the ice patch was large. Based on comparison with the chronology of natural bone and antler samples from the site, the greater number of finds of this date may also reflect a period of increased hunting. </jats:p

Interpreting archaeological site-formation processes at a mountain ice patch: A case study from Langfonne, Norway

In the context of global warming, ice patches are increasingly important foci of high-elevation archaeology. Langfonne in Jotunheimen, central southern Norway, is uniquely suited to provide a window onto site formation processes and taphonomy in this novel archaeological setting. Here the site record from systematic survey includes the largest number of arrows, bones and antlers from a single ice patch worldwide. Combining data from these finds with the results of glaciological investigations provides an opportunity to interpret the influence of archaeological site formation processes and taphonomy on chronological and spatial patterning. It is inferred that the spatial patterning of artefacts at Langfonne is partly a result of displacement by ice movement, meltwater and other natural processes. Nevertheless, the finds yield information regarding past hunting practices and the extent of ice at different times. An early cluster of finds from c.6000 cal yr BP may result from ice deformation which has brought early objects to the surface. The number of arrows increases from c. 1700 cal yr BP onwards, peaking around c.1200 cal yr BP. Artefacts from this period show a wide spatial distribution indicating both the preferential survival of more recent finds and that they were lost when the ice patch was large. Based on comparison with the chronology of natural bone and antler samples from the site, the greater number of finds of this date may also reflect a period of increased hunting. </jats:p

Psychological determinants of whole-body endurance performance

Background: No literature reviews have systematically identified and evaluated research on the psychological determinants of endurance performance, and sport psychology performance-enhancement guidelines for endurance sports are not founded on a systematic appraisal of endurance-specific research. Objective: A systematic literature review was conducted to identify practical psychological interventions that improve endurance performance and to identify additional psychological factors that affect endurance performance. Additional objectives were to evaluate the research practices of included studies, to suggest theoretical and applied implications, and to guide future research. Methods: Electronic databases, forward-citation searches, and manual searches of reference lists were used to locate relevant studies. Peer-reviewed studies were included when they chose an experimental or quasi-experimental research design, a psychological manipulation, endurance performance as the dependent variable, and athletes or physically-active, healthy adults as participants. Results: Consistent support was found for using imagery, self-talk, and goal setting to improve endurance performance, but it is unclear whether learning multiple psychological skills is more beneficial than learning one psychological skill. The results also demonstrated that mental fatigue undermines endurance performance, and verbal encouragement and head-to-head competition can have a beneficial effect. Interventions that influenced perception of effort consistently affected endurance performance. Conclusions: Psychological skills training could benefit an endurance athlete. Researchers are encouraged to compare different practical psychological interventions, to examine the effects of these interventions for athletes in competition, and to include a placebo control condition or an alternative control treatment. Researchers are also encouraged to explore additional psychological factors that could have a negative effect on endurance performance. Future research should include psychological mediating variables and moderating variables. Implications for theoretical explanations of endurance performance and evidence-based practice are described

Preclinical efficacy of azacitidine and venetoclax for infant KMT2A-rearranged acute lymphoblastic leukemia reveals a new therapeutic strategy

Infants with KMT2A-rearranged B-cell acute lymphoblastic leukemia (ALL) have a dismal prognosis. Survival outcomes have remained static in recent decades despite treatment intensification and novel therapies are urgently required. KMT2A-rearranged infant ALL cells are characterized by an abundance of promoter hypermethylation and exhibit high BCL-2 expression, highlighting potential for therapeutic targeting. Here, we show that hypomethylating agents exhibit in vitro additivity when combined with most conventional chemotherapeutic agents. However, in a subset of samples an antagonistic effect was seen between several agents. This was most evident when hypomethylating agents were combined with methotrexate, with upregulation of ATP-binding cassette transporters identified as a potential mechanism. Single agent treatment with azacitidine and decitabine significantly prolonged in vivo survival in KMT2A-rearranged infant ALL xenografts. Treatment of KMT2A-rearranged infant ALL cell lines with azacitidine and decitabine led to differential genome-wide DNA methylation, changes in gene expression and thermal proteome profiling revealed the target protein-binding landscape of these agents. The selective BCL-2 inhibitor, venetoclax, exhibited in vitro additivity in combination with hypomethylating or conventional chemotherapeutic agents. The addition of venetoclax to azacitidine resulted in a significant in vivo survival advantage indicating the therapeutic potential of this combination to improve outcome for infants with KMT2A-rearranged ALL

The long-term prediction of return to work following serious accidental injuries: A follow up study

Background Considerable indirect costs are incurred by time taken off work following accidental injuries. The aim of this study was to predict return to work following serious accidental injuries. Method 121 severely injured patients were included in the study. Complete follow-up data were available for 85 patients. Two weeks post trauma (T1), patients rated their appraisal of the injury severity and their ability to cope with the injury and its job-related consequences. Time off work was assessed at one (T2) and three years (T3) post accident. The main outcome was the number of days of sick leave taken due to the accidental injury. Results The patients' appraisals a) of the injury severity and b) of their coping abilities regarding the accidental injury and its job-related consequences were significant predictors of the number of sick-leave days taken. Injury severity (ISS), type of accident, age and gender did not contribute significantly to the prediction. Conclusions Return to work in the long term is best predicted by the patients' own appraisal of both their injury severity and the ability to cope with the accidental injury

The impact of ivermectin on onchocerciasis in villages co-endemic for lymphatic filariasis in an area of onchocerciasis recrudescence in Burkina Faso

In Burkina Faso, onchocerciasis was no longer a public health problem when the WHO Onchocerciasis Control Programme in West Africa closed at the end in 2002. However, epi-demiological surveillance carried out from November 2010 to February of 2011, showed a recrudescence of infection in the Cascades Region. This finding was made at a time when ivermectin, a drug recommended for the treatment of both onchocerciasis and lymphatic fila-riasis, had been distributed in this area since 2004 for the elimination of lymphatic filariasis. It was surprising that ivermectin distributed for treating lymphatic filariasis had not prevented the recrudescence of onchocerciasis. Faced with this situation, the aim of our study was to evaluate the effectiveness of ivermectin on the onchocerciasis parasite. The percentage reduction in microfilarial load after treatment with ivermectin was used as a proxy measure for assessing possible resistance. A cohort study was carried out with 130 individuals who had tested positive for microfilariae of Onchocerca volvulus in 2010 using microscopic examination of skin-snip biopsies from five endemic villages. Subjects were followed from July 2011 to June 2012. The microfilarial load of each individual was enumerated by skin-snip biopsy in 2010, prior to the first ivermectin treatment against onchocerciasis under community guidelines. All individuals received two ivermectin treatments six months apart. In 2012, the microfilarial loads were determined again, six months after the second round of ivermectin and the reductions in parasite loads were calculated to measure the impact of the drug. The percentage reduction of the microfilarial loads ranged from 87% to 98% in the vil-lages. In all villages, there was a statistically significant difference between the average microfilarial loads in 2010 and 2012. The level of reduction of microfilarial loads suggests that ivermectin is effective against the recrudescent population of O. volvulus in Cascades Region of Burkina Faso. Further investigations would be necessary to determine the causes of the recrudescence of onchocerciasis. (For French language abstract, see S1 Alternative Language Abstract—Translation of the Abstract into French by the authors.)

Effects of Global Warming on Ancient Mammalian Communities and Their Environments

Current global warming affects the composition and dynamics of mammalian communities and can increase extinction risk; however, long-term effects of warming on mammals are less understood. Dietary reconstructions inferred from stable isotopes of fossil herbivorous mammalian tooth enamel document environmental and climatic changes in ancient ecosystems, including C(3)/C(4) transitions and relative seasonality.Here, we use stable carbon and oxygen isotopes preserved in fossil teeth to document the magnitude of mammalian dietary shifts and ancient floral change during geologically documented glacial and interglacial periods during the Pliocene (approximately 1.9 million years ago) and Pleistocene (approximately 1.3 million years ago) in Florida. Stable isotope data demonstrate increased aridity, increased C(4) grass consumption, inter-faunal dietary partitioning, increased isotopic niche breadth of mixed feeders, niche partitioning of phylogenetically similar taxa, and differences in relative seasonality with warming.Our data show that global warming resulted in dramatic vegetation and dietary changes even at lower latitudes (approximately 28 degrees N). Our results also question the use of models that predict the long term decline and extinction of species based on the assumption that niches are conserved over time. These findings have immediate relevance to clarifying possible biotic responses to current global warming in modern ecosystems

Towards the clinical implementation of pharmacogenetics in bipolar disorder.

BackgroundBipolar disorder (BD) is a psychiatric illness defined by pathological alterations between the mood states of mania and depression, causing disability, imposing healthcare costs and elevating the risk of suicide. Although effective treatments for BD exist, variability in outcomes leads to a large number of treatment failures, typically followed by a trial and error process of medication switches that can take years. Pharmacogenetic testing (PGT), by tailoring drug choice to an individual, may personalize and expedite treatment so as to identify more rapidly medications well suited to individual BD patients.DiscussionA number of associations have been made in BD between medication response phenotypes and specific genetic markers. However, to date clinical adoption of PGT has been limited, often citing questions that must be answered before it can be widely utilized. These include: What are the requirements of supporting evidence? How large is a clinically relevant effect? What degree of specificity and sensitivity are required? Does a given marker influence decision making and have clinical utility? In many cases, the answers to these questions remain unknown, and ultimately, the question of whether PGT is valid and useful must be determined empirically. Towards this aim, we have reviewed the literature and selected drug-genotype associations with the strongest evidence for utility in BD.SummaryBased upon these findings, we propose a preliminary panel for use in PGT, and a method by which the results of a PGT panel can be integrated for clinical interpretation. Finally, we argue that based on the sufficiency of accumulated evidence, PGT implementation studies are now warranted. We propose and discuss the design for a randomized clinical trial to test the use of PGT in the treatment of BD

“I would rather be told than not know” - A qualitative study exploring parental views on identifying the future risk of childhood overweight and obesity during infancy

BACKGROUND: Risk assessment tools provide an opportunity to prevent childhood overweight and obesity through early identification and intervention to influence infant feeding practices. Engaging parents of infants is paramount for success however; the literature suggests there is uncertainty surrounding the use of such tools with concerns about stigmatisation, labelling and expressions of parental guilt. This study explores parents' views on identifying future risk of childhood overweight and obesity during infancy and communicating risk to parents. METHODS: Semi-structured qualitative interviews were conducted with 23 parents and inductive, interpretive and thematic analysis performed. RESULTS: Three main themes emerged from the data: 1) Identification of infant overweight and obesity risk. Parents were hesitant about health professionals identifying infant overweight as believed they would recognise this for themselves, in addition parents feared judgement from health professionals. Identification of future obesity risk during infancy was viewed positively however the use of a non-judgemental communication style was viewed as imperative. 2) Consequences of infant overweight. Parents expressed immediate anxieties about the impact of excess weight on infant ability to start walking. Parents were aware of the progressive nature of childhood obesity however, did not view overweight as a significant problem until the infant could walk as viewed this as a point when any excess weight would be lost due to increased energy expenditure. 3) Parental attributions of causality, responsibility, and control. Parents articulated a high level of personal responsibility for preventing and controlling overweight during infancy, which translated into self-blame. Parents attributed infant overweight to overfeeding however articulated a reluctance to modify infant feeding practices prior to weaning. CONCLUSION: This is the first study to explore the use of obesity risk tools in clinical practice, the findings suggest that identification, and communication of future overweight and obesity risk is acceptable to parents of infants. Despite this positive response, findings suggest that parents' acceptance to identification of risk and implementation of behaviour change is time specific. The apparent level of parental responsibility, fear of judgement and self-blame also highlights the importance of health professionals approach to personalised risk communication so feelings of self-blame are negated and stigmatisation avoided