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This study uses luminescence and 14C accelerator mass spectrometry procedures to date relevant glaciofluvial and glacial deposits from the south-central and southeastern Pyrenees (Andorra–France–Spain). We distinguish two types of end-moraine complexes: (1) those in which at least a far-flung moraine exists beyond a frequently nested end-moraine complex (the most common) and (2) those in which a close-nested end moraine encompasses at least two glacial cycles. Both types formed within six distinctive glacial intervals: (1) A penultimate glacial cycle during Marine Oxygen Isotope Stage (MIS) 6 and older glaciofluvial terraces occurred beyond the range of the luminescence dating method. (2) An early glacial advance in MIS 5d (~97 −15/+19 ka) was followed by glacial retreat during MIS 5c (< 91 ± 9 ka). (3) The last maximum ice extent (LMIE) was in early MIS 4 (~74 ± 4.5 ka). (4) Unexpectedly, glaciers thinned during the second half of MIS 3 (~39 −6/+11 ka). (5) During the MIS 3–2 transition, glaciers subsequently fluctuated behind the LMIE limits. (6) The global last glacial maximum (LGM) started as early as ~26.6 ± 0.365 ka b2k, and the corresponding end moraines were built behind the LMIE limits or merged with it, forming close-nested moraines.
We study the existence and structure of branch points in two-phase free boundary problems. More precisely, we construct a family of minimizers to an Alt–Caffarelli–Friedman-type functional whose free boundaries contain branch points in the strict interior of the domain. We also give an example showing that branch points in the free boundary of almost-minimizers of the same functional can have very little structure. This last example stands in contrast with recent results of De Philippis, Spolaor and Velichkov on the structure of branch points in the free boundary of stationary solutions.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Negative interactions with humans resulting from livestock predation is a major factor influencing the decline of African lion Panthera leo populations across Africa. Here we investigate lion depredation within two Maasai communities in southern Kenya where people and lions coexist in the absence of any formal protected areas. We explore the factors that increase the frequency and severity of lion attacks on pastoralists and their livestock and assess the effectiveness of livestock guarding to reduce damage. Finally, we examine in which circumstances lion depredation triggers retaliation by people. Over a period of 26 months, lions attacked livestock 29 times, resulting in 41 livestock deaths and 19 injuries. There were also two attacks on people. Lions preferred cattle over the more numerous sheep and goats. Attacks on livestock occurred mostly during the dry season and were not affected by changes in prey density or variation in pastoral settlement that brought livestock into closer proximity with lions. Livestock were guarded during 48.2% of lion attacks. Active guarding at pasture disrupted the majority of lion attacks, resulting in lower mortality rates. Passive guarding in corrals at night also disrupted attacks but did not lead to lower livestock mortality.
Cognitive behavioural therapy for psychosis (CBTp) is a recommended treatment for psychotic experiences, but its effectiveness has been questioned. One way of addressing this may be to tailor therapy materials to the phenomenology of specific psychotic experiences.
In this study, we investigated the acceptability of a novel treatment manual for subtypes of ‘voice-hearing’ experiences (i.e. auditory verbal hallucinations). An uncontrolled, single-arm design was used to assess feasibility and acceptability of using the manual in routine care for people with frequent voice-hearing experiences.
The manual was delivered on a smart tablet and incorporated recent research evidence and theory into its psychoeducation materials. In total, 24 participants completed a baseline assessment; 19 started treatment, 15 completed treatment and 12 participants completed a follow-up assessment (after 10 sessions of using the manual).
Satisfaction with therapy scores and acceptability ratings were high, while completion rates suggested that the manual may be more appropriate for help with participants from Early Intervention in Psychosis services rather than Community Mental Health Teams.
Within-group changes in symptom scores suggested that overall symptom severity of hallucinations – but not other psychosis features, or beliefs about voices – are likely to be the most appropriate primary outcome for further evaluation in a full randomised controlled trial.
Validation of biomarkers reporting on the intake or bioactivity of foods requests that the dose-response behaviour of relevant nutrients be known. Establishing this relationship is, however, challenging because of the complex composition of foods. In addition, humans respond differently to caloric intake depending on their metabolic health. By allowing the measure of multi-molecular profiles, omics technologies provide better insights into these issues. We have previously measured the response of the blood cell transcriptome of normal weight (NW) and obese (OB) men to increasing caloric doses of a high-fat meal (HFM). We now describe the dose-response of the serum metabolome of these subjects and discuss the results in light of the transcriptomic response.
Material and Methods
In a randomized crossover study, we challenged 19 NW and 18 OB men with 500, 1’000, and 1’500 kcal HFM. The blood cell transcriptome was measured before and 2, 4, and 6 h after meal ingestion. The untargeted serum metabolome was assessed at the same time points. The genes and metabolites responding postprandially in a dose-dependant manner were identified.
Among the 1’385 features with a postprandial response, 178 showed a significant dose-response between meals. A majority of them increased (amino acids, bile salt conjugates, metabolites in urea cycle), whereas circa one fifth, indicative of an endogenous response, decreased (e.g. carnitine esters). Overall, the postprandial metabolome showed caloric saturation, the metabolome after 1’500 kcal HFM being quantitatively only marginally different than after 1’000 kcal. Although a subset of metabolites responded differently to the caloric increase, the postprandial metabolomes of NW and OB subjects were, overall, mostly characterized by their similarity. This finding contrasted with the blood cell transcriptome, which identified a subset of OB subjects whose expression of genes of the oxidative phosphorylation pathway was, compared to the NW subjects, more increased after ingestion of 1’500 kcal HFM.
We report, for the first time, the response of the human serum metabolome to increasing caloric doses of a meal. The saturation observed between 1’000 and 1’500 kcal reflects on the control mechanisms regulating the metabolites entering the blood circulation. Interestingly, combining the analysis of the serum metabolome with the blood cell transcriptome indicated that the elevated cellular oxidative response to 1’500 kcal HFM in a subset of OB subjects results from a dysregulation of systemic cellular mechanisms in response to food intake, rather than from changes in gastrointestinal processing.
This paper presents the results of the work of the new field initiative launched by the British Museum at the Darband-i Rania pass in the Kurdistan Region of Iraq. The pass is located at the northeastern corner of Lake Dokan, where, though now subsumed into the lake, the Lower Zab flows from the Peshdar into the Rania Plain. It is a strategic location on a major route from Mesopotamia into Iran, and control of both the road and the river must always have been important. The aim of the work, which commenced in autumn of 2016, is to explore a cluster of sites that commanded the pass, with a particular focus on the first millennium b.c. Excavation is being carried out principally at two sites: Qalatga Darband, a large fortified site at the western end of the pass, and Usu Aska, a fort inside the pass itself. The occupations of these two sites are predominantly Parthian and Assyrian respectively. Smaller operations have also been carried out at Murad Rasu, a multi-period site situated on a headland across the waters on the southern shore of Lake Dokan. The results have included the discovery at Qalatga Darband of a monumental complex built of stone and roofed with terracotta roof tiles containing the smashed remains of Hellenistic statuary. Other features indicative of Hellenistic material culture are Mediterranean-type oil-presses and Corinthian column bases and capitals. At Usu Aska remains are being uncovered of an Assyrian fortification of massive proportions.
The production and use of masks at multiple scales and in diverse contexts is a millennia-long tradition in Mesoamerica. In this paper, we explore some implications of Mesoamerican masking practices in light of materiality studies and the archaeology of the senses. We also discuss a collection of 22 masks, miniature masks and representations of masks from the lower Río Verde valley of coastal Oaxaca, Mexico. The iconography of these artefacts as well as their recovery from well-documented archaeological contexts inform our interpretations of masking practices during an approximately 2000-year span of the Formative period (2000 bc–ad 250). Specifically, we argue that these masking-related artefacts index sociocultural changes in the region, from the first villages and the advent of ceramic technology during the Early Formative period (2000–1000 bc) to a time of increasing consolidation of iconographic influence in the hands of the elite in the final centuries before the Classic period. As indicated by their continued use today, masks have long been intimates of communal activities in Oaxaca.
The widespread use of herbicides in cropping systems has led to the evolution of resistance in major weeds. The resultant loss of herbicide efficacy is compounded by a lack of new herbicide sites of action, driving demand for alternative weed control technologies. While there are many alternative methods for control, identifying the most appropriate method to pursue for commercial development has been hampered by the inability to compare techniques in a fair and equitable manner. Given that all currently available and alternative weed control methods share an intrinsic energy consumption, the aim of this review was to compare methods based on energy consumption. Energy consumption was compared for chemical, mechanical, and thermal weed control technologies when applied as broadcast (whole-field) and site-specific treatments. Tillage systems, such as flex-tine harrow (4.2 to 5.5 MJ ha−1), sweep cultivator (13 to 14 MJ ha−1), and rotary hoe (12 to 17 MJ ha−1) consumed the least energy of broadcast weed control treatments. Thermal-based approaches, including flaming (1,008 to 4,334 MJ ha−1) and infrared (2,000 to 3,887 MJ ha−1), are more appropriate for use in conservation cropping systems; however, their energy requirements are 100- to 1,000-fold greater than those of tillage treatments. The site-specific application of weed control treatments to control 2-leaf-stage broadleaf weeds at a density of 5 plants m−2 reduced energy consumption of herbicidal, thermal, and mechanical treatments by 97%, 99%, and 97%, respectively. Significantly, this site-specific approach resulted in similar energy requirements for current and alternative technologies (e.g., electrocution [15 to 19 MJ ha−1], laser pyrolysis [15 to 249 MJ ha−1], hoeing [17 MJ ha−1], and herbicides [15 MJ ha−1]). Using similar energy sources, a standardized energy comparison provides an opportunity for estimation of weed control costs, suggesting site-specific weed management is critical in the economically realistic implementation of alternative technologies.
Seven AMS radiocarbon dates (1950–1525 cal BC) from controlled contexts demonstrate Early Formative period occupation in coastal Oaxaca, Mexico. These dated elements from the site of La Consentida include hearths, occupational surfaces, carbon adhering to pottery from a midden, and human bone collagen processed with XAD purification. They were excavated from primary contexts and do not represent redeposited materials. An eighth sample, dated to the Middle Formative period, is considered postoccupational. The diversity of dated deposits and features, their distribution, and their overlapping calibrated ranges indicate settlement by an initial Early Formative period village.
Our research group recently evaluated a minimally invasive surgical procedure in order to inform a reimbursement decision. The application for funding was designed around the study selection criteria from a single pivotal randomized controlled trial (RCT). The aim of this study review was to evaluate the safety and effectiveness of this minimally invasive surgical procedure, and document challenges faced in evaluating a technology based on a highly targeted population.
A systematic literature search of four biomedical databases was conducted (PubMed, Embase, Cochrane library, York CRD) up to 8 August 2017. Specific elements related to the population were patient age, together with level and duration of pain. Primary effectiveness outcomes included pain, patient reported quality of life, mortality and adverse events. The included RCTs were critically appraised against the Cochrane risk of bias tool. Meta-analysis was not possible due to the limited availability of evidence with consistent outcomes.
From 4,718 search results, only one pivotal RCT specifically met the inclusion criteria, which demonstrated favorable safety and effectiveness of the procedure; however, the sample population in the trial had limited external validity to the proposed reimbursement population and follow-up was limited to six months. As a result, the selection criteria were broadened to better reflect the manner in which the service may be provided in clinical practice, and capture longer-term safety concerns. Four additional RCTs were included, which provided contradictory results.
The results of this review identified two important issues in evaluating a health technology where the assessment has been focused to the results of a single trial. In particular, the generalizability of a trial is defined by the demographic distribution of the sample, not the selection criteria. Designing the review selection criteria around the selection criteria for a single trial can have consequences for a funding decision.
The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)–pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D–pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (Prace difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (Prace difference=0·56). Among EA, the 25(OH)D–FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.
Background: There is growing trend for some surgical procedures previously performed in hospitals to be done in alternative settings, including office-based facilities. There has been some safety concerns reported in the media, which document serious adverse events following procedures performed in an office-based setting. To understand the current regulatory oversight of surgery in this setting ASERNIP-S conducted a review of the legislative and accreditation process governing these facilities in Australia.
Methods: Using rapid review methodology, internet searches targeted government Web sites for relevant publicly-available documents. Use of consolidated versions of legislative instruments ensured currency of information. Standards were sourced directly from the issuing authorities or those that oversee the accreditation process.
Results: Within Australia, healthcare facilities for surgery and their licensing are defined by each state and territory, which results in significant jurisdictional variation. These variations relate to the need for anesthesia beyond conscious sedation and listing of procedures in legislative instruments. In 2013, Australia adopted National Safety and Quality Health Service standards (NSQHS standards) for the accreditation of hospitals and day surgery centers; however, there is no NSQHS standard for office-based facilities. The main legislative driver for compliance is access to reimbursement schemes for service delivery.
Conclusions: The legislative and accreditation framework creates a situation whereby healthcare facilities that provide services outside the various legal definitions of surgery and those not covered by a reimbursement scheme, can operate without licensing and accreditation oversight. This situation exposes patients to potential increased risk of harm when receiving treatment in such unregulated facilities.
Network meta-analysis (NMA) is a statistical technique for making direct and indirect comparisons between different treatment and control groups. Despite its many advantages, NMA may be misleading when evaluating networks that are disconnected, inconsistent or of low reliability and validity. We review how well the analysis of trials of adjunctive psychosocial treatment in bipolar disorder is served by NMA. We conclude with recommendations for future treatment trials in bipolar disorder and guidelines for NMAs.
FFQ, food diaries and 24 h recall methods represent the most commonly used dietary assessment tools in human studies on nutrition and health, but food intake biomarkers are assumed to provide a more objective reflection of intake. Unfortunately, very few of these biomarkers are sufficiently validated. This review provides an overview of food intake biomarker research and highlights present research efforts of the Joint Programming Initiative ‘A Healthy Diet for a Healthy Life’ (JPI-HDHL) Food Biomarkers Alliance (FoodBAll). In order to identify novel food intake biomarkers, the focus is on new food metabolomics techniques that allow the quantification of up to thousands of metabolites simultaneously, which may be applied in intervention and observational studies. As biomarkers are often influenced by various other factors than the food under investigation, FoodBAll developed a food intake biomarker quality and validity score aiming to assist the systematic evaluation of novel biomarkers. Moreover, to evaluate the applicability of nutritional biomarkers, studies are presently also focusing on associations between food intake biomarkers and diet-related disease risk. In order to be successful in these metabolomics studies, knowledge about available electronic metabolomics resources is necessary and further developments of these resources are essential. Ultimately, present efforts in this research area aim to advance quality control of traditional dietary assessment methods, advance compliance evaluation in nutritional intervention studies, and increase the significance of observational studies by investigating associations between nutrition and health.