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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.
The alternative mitigation program that the Bureau of Land Management (BLM) established in 2008 to address impacts to the archaeological resources in the Permian Basin of southeastern New Mexico, now one of the most active of the nation's oil and gas energy fields, has supported more than $10 million in field research programs and is poised to be able to fund about $1 million in field research annually for the foreseeable future. The financial success of the program is mirrored by the program's outstanding contributions to our understanding of the Permian Basin's long and complex history of human occupation. Surprisingly, although other public lands under the auspices of the BLM are seeing similar rates of energy development, the critical elements of this program have not been picked up elsewhere in the BLM. The Permian Basin program appears doomed to be an example of a “one-off” alternative mitigation solution. The factors barring more widespread adoption include the ebb and flow of energy production activity, complications arising from mixed land status and the ability to work across jurisdictional boundaries, hesitation to change procedures that are working adequately for the time being, and a lack of capacity to institute systemic change.
Childhood maltreatment (CM) plays an important role in the development of major depressive disorder (MDD). The aim of this study was to examine whether CM severity and type are associated with MDD-related brain alterations, and how they interact with sex and age.
Within the ENIGMA-MDD network, severity and subtypes of CM using the Childhood Trauma Questionnaire were assessed and structural magnetic resonance imaging data from patients with MDD and healthy controls were analyzed in a mega-analysis comprising a total of 3872 participants aged between 13 and 89 years. Cortical thickness and surface area were extracted at each site using FreeSurfer.
CM severity was associated with reduced cortical thickness in the banks of the superior temporal sulcus and supramarginal gyrus as well as with reduced surface area of the middle temporal lobe. Participants reporting both childhood neglect and abuse had a lower cortical thickness in the inferior parietal lobe, middle temporal lobe, and precuneus compared to participants not exposed to CM. In males only, regardless of diagnosis, CM severity was associated with higher cortical thickness of the rostral anterior cingulate cortex. Finally, a significant interaction between CM and age in predicting thickness was seen across several prefrontal, temporal, and temporo-parietal regions.
Severity and type of CM may impact cortical thickness and surface area. Importantly, CM may influence age-dependent brain maturation, particularly in regions related to the default mode network, perception, and theory of mind.
Sauropod bone histology has provided a great deal of insight into the life history of these enormous animals. However, because of high growth rates, annual growth rings are not common in sauropod long bones, so directly measuring growth rates and determining sexual maturity require alternative measures. Histological ontogenetic stages (HOS) have been established to describe the changes in bone histology through development for basal Macronaria and Diplodocoidea, and subsequently for Titanosauria. Despite this, the current HOS model is not able to discriminate bone tissues in late ontogeny, when sauropods had reached asymptotic size and continued to live into senescence but their long bones became extensively remodeled by secondary osteons and all primary bone was destroyed. Here we establish remodeling stages (RS) to characterize the Haversian bone development through ontogeny in eight sauropod taxa (Apatosaurinae, Giraffatitan brancai, Camarasaurus spp., Dicraeosaurus spp., Ampelosaurus atacis, Phuwiangosaurus sirindhornae, Magyarosaurus dacus, and Alamosaurus sanjuanensis) and find significant correlation of RS with corresponding femur length (CFL) for the studied taxa, with the exception of Dicraeosaurus and Magyarosaurus. Remodeling stages are based on the maximum number of observable generations of crosscutting osteons from the innermost, mid-, and outermost part of the cortex. The correlation with CFL indicates that secondary osteons present an ontogenetic signal that could extend the histological ontogenetic stages. Remodeling stages also provide additional insight into the changes in histology through ontogeny for Sauropoda. This method has the potential to be used in other taxa, such as thyreophorans and many ornithischians, that develop Haversian tissue through development.
Most of the previous studies attempted to disentangle the relationship between disability and depressive symptoms were limited to observation periods of only few years. Moreover, evidence is missing regarding the complex co-occurrence of disability and depressive symptoms in old age in Germany. In order to close the research gap, we aimed at disentangling the complex co-occurrence of disability and depressive symptoms in old age in Germany over a longer time frame.
Based on data from a representative survey of the German general population aged 75 years and older, the course of disability as well as depressive symptoms was observed every 1.5 years over six waves. While disability was quantified by the Lawton and Brody Instrumental Activities of Daily Living scale, the Geriatric Depression Scale was used to measure depressive symptoms. Taking into account the complex co-occurrence of depressive symptoms and disability, a panel vector autoregressive model was used. By taking the first differences, unobserved heterogeneity was taken into account.
In the total sample and in both sexes, we revealed a robust positive association between an initial change in depressive symptoms and subsequent changes in disability. No robust association between an initial change in disability and a subsequent change in depressive symptoms was detected.
Our findings highlight the importance of changes in depressive symptoms for future changes in disability in old age.
If patients are treated according to their personal preferences, depression treatment success is higher. It is not known which treatment options for late-life depression are preferred by patients aged 75 years and over and whether there are determinants of these preferences.
The data were derived from the German “Late-life depression in primary care: needs, health care utilization, and costs (AgeMooDe)” study. Patients aged 75+ years (N = 1,230) were recruited from primary care practices. Depressive symptoms were determined using the Geriatric Depression Scale (GDS-15). Support for eight treatment options was determined.
Medication, psychotherapy, talking to friends and family, and exercise were the preferred treatment options. Having a GDS score ≥ 6 significantly lowered the endorsement of some treatment options. For each treatment option, the probability of choosing the indecisive category “I do not know” was significantly increased in participants with moderate depressive symptoms.
Depressive symptoms influence the preference for certain treatment options and also increase indecision in patients. The high preference for psychotherapy suggests a much higher demand for late-life psychotherapy in the future. Healthcare systems should begin to prepare to meet this anticipated need. Future studies should include previous experience with treatment methods as a confounding variable.
The Permian Basin Programmatic Agreement (PA) is an alternative form of Section 106 compliance offered mainly to the oil and gas industry in southeastern New Mexico for projects located on Bureau of Land Management (BLM) land. Proponents of projects within the PA area may contribute to a dedicated archaeological research fund in lieu of contracting for project specific archaeological surveys, provided their proposed projects avoid recorded archaeological sites. Dedicated funding goes toward research on the archaeology and history of southeastern New Mexico. The PA calls for the consulting parties to evaluate its effectiveness during its seventh year of implementation. As a result of that recent evaluation in May 2015, the PA will be extended for 10 additional years. We discuss the reasons for the PA, successes and missteps during its first seven years, and ways that the Permian Basin PA might be used as a model elsewhere.
Although evidence exists for abnormal brain function across various
anxiety disorders, direct comparison of neural function across diagnoses
is needed to elicit abnormalities common across disorders and those
distinct to a particular diagnosis.
To delineate common and distinct abnormalities within generalised anxiety
(GAD), panic and social anxiety disorder (SAD) during affective
Fifty-nine adults (15 with GAD, 15 with panic disorder, 14 with SAD, and
15 healthy controls) underwent functional magnetic resonance imaging
while completing a facial emotion matching task with fearful, angry and
Greater differential right amygdala activation to matching fearful
v. happy facial expressions related to greater
negative affectivity (i.e. trait anxiety) and was heightened across all
anxiety disorder groups compared with controls. Collapsing across
emotional face types, participants with panic disorder uniquely displayed
greater posterior insula activation.
These preliminary results highlight a common neural basis for clinical
anxiety in these diagnoses and also suggest the presence of
Paired isotope dilution – thermal ionization mass spectrometry (ID-TIMS) and secondary ion mass spectrometry (SIMS) zircon U–Pb data elucidate geochronological relations in the historically important Knaben molybdenum mining district, Sveconorwegian Orogen, south Norway. This polyphase district provided c. 8.5 Mt of ore with a grade of 0.2%. It consists of mineralized quartz veins, silica-rich gneiss, pegmatites and aplites associated with a heterogeneous, locally sulphide-bearing, amphibolites facies gneiss called Knaben Gneiss, and hosted in a regional-scale monotonous, commonly weakly foliated, granitic gneiss. An augen gneiss at the Knaben I deposit yields a 1257±6 Ma magmatic zircon age, dating the pre-Sveconorwegian protolith of the Knaben Gneiss. Mineralized and non-mineralized granitic gneiss samples at the Knaben II and Kvina deposits contain some 1488–1164 Ma inherited zircon and yield consistent intrusion ages of 1032±4, 1034±6 and 1036±6 Ma. This age links magmatism in the district to the regional 1050–1020 Ma Sirdal I-type granite suite, corresponding to voluminous crustal melting during the Sveconorwegian orogeny. A high-U, low-Th/U zircon rim is present in all samples. It defines several age clusters between 1039±6 and 1009±7 Ma, peaking at c. 1016 Ma and overlapping with a monazite age of 1013±5 Ma. The rim records protracted hydrothermal activity, which started during the main magmatic event and outlasted it. This process was coeval with regional high-grade Sveconorwegian metamorphism. Molybdenum deposition probably started during this event when silica-rich mineralizing fluids or hydrous magmas were released from granite magma batches. An analogy between the Knaben district and shallow, short-lived porphyry Mo deposits is inappropriate.
Fe-Al alloys with about 55 to 65 at.% Al undergo a eutectoid transformation at 1095 °C: Fe5Al8 (ε) ↔ FeAl + FeAl2. Hence, as-cast Fe-Al alloys in this composition range show a very fine-scaled lamellar microstructure (average lamellar spacing below 500 nm) consisting of the two phases FeAl and FeAl2. The microstructure looks similar to the α2 + γ lamellar microstructure of Ti-Al-based alloys, which is known for having well-balanced properties in terms of creep, ductility and strength. However, there is limited knowledge about the properties of Fe-Al-based alloys in this composition range. In this study, a series of as-cast as well as heat-treated Fe-Al alloys with compositions between 57 and 63 at.% Al were investigated. The microstructures and crystal structures were analysed by scanning electron microscopy (SEM) and X-ray diffraction (XRD), respectively. The composition dependence of all transition temperatures was obtained by differential thermal analysis (DTA).
In 2008, the Carlsbad Field Office of the Bureau of Land Management (BLM) made a fundamental change in how they work with the energy industry in the Permian Basin of southeastern New Mexico, one of the nation's busiest “oil patches.” Through a collaborative effort that involved the Bureau of Land Management, the New Mexico State Historic Preservation Officer, the Advisory Council on Historic Preservation, the Mescalero Apache Tribe, and industry representatives, they developed and implemented the Permian Basin Memorandum of Agreement (MOA). This agreement allows energy development proponents to contribute funds to archaeological research in lieu of spending an equivalent amount of money on traditional archaeological field survey. The mitigation program governs how BLM addresses long-term damage and cumulative impacts to archaeological resources as new development proceeds in the Permian Basin MOA area. Now in its fifth year, the program has succeeded in key ways: industry has gained control over schedules and time, while archaeologists have gained control over where and how they do archaeology. Key lessons have been learned along the way: The funding mechanisms of the program work well, but doing archaeology through a collaborative working group takes a lot of time and energy.
Different lifestyle patterns across Europe may influence plasma concentrations of B-vitamins and one-carbon metabolites and their relation to chronic disease. Comparison of published data on one-carbon metabolites in Western European regions is difficult due to differences in sampling procedures and analytical methods between studies. The present study aimed, to compare plasma concentrations of one-carbon metabolites in Western European regions with one laboratory performing all biochemical analyses. We performed the present study in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort among 5446 presumptively healthy individuals. Quantile regression was used to compare sex-specific median concentrations between Northern (Denmark and Sweden), Central (France, Germany, The Netherlands and United Kingdom) and Southern (Greece, Spain and Italy) European regions. The lowest folate concentrations were observed in Northern Europe (men, 10·4 nmol/l; women, 10·7 nmol/l) and highest concentrations in Central Europe. Cobalamin concentrations were slightly higher in Northern Europe (men, 330 pmol/l; women, 352 pmol/l) compared with Central and Southern Europe, but did not show a clear north–south gradient. Vitamin B2 concentrations were highest in Northern Europe (men, 22·2 nmol/l; women, 26·0 nmol/l) and decreased towards Southern Europe (Ptrend< 0·001). Vitamin B6 concentrations were highest in Central Europe in men (77·3 nmol/l) and highest in the North among women (70·4 nmol/l), with decreasing concentrations towards Southern Europe in women (Ptrend< 0·001). In men, concentrations of serine, glycine and sarcosine increased from the north to south. In women, sarcosine increased from Northern to Southern Europe. These findings may provide relevant information for the study of regional differences of chronic disease incidence in association with lifestyle.
The Briar Creek Bonebed (Artinskian, Nocona Formation) in Archer County is one of the richest sources of Dimetrodon bones in the Lower Permian of Texas, USA. Based on size, a small (D. natalis), an intermediate (D. booneorum), and a large species (D. limbatus) have been described from this locality. It has been proposed that these traditionally recognised species represent an ontogenetic series of only one species. However, the ontogenetic series hypothesis is inconsistent with the late ontogenetic state of the small bones, as suggested by their osteology and degree of ossification. Histological analysis of newly excavated material from the Briar Creek Bonebed has resolved some of the discretion between these two competing hypothesis, confirming the coexistence of a small (D. natalis) with at least one larger Dimetrodon species. An external fundamental system is present in the largest sampled long bones identified as D. natalis. The histology of D. natalis postcrania is described as incipient fibro lamellar bone. This tissue is a combination of parallel-fibred and woven-fibred bone that is highly vascularised by incipient primary osteons. The species status of D. booneorum and D. limbatus remain unresolved.
The development of late-onset Alzheimer's disease (LOAD) is under strong genetic control and there is great interest in the genetic variants that confer increased risk. The Alzheimer's disease risk gene, growth factor receptor bound protein 2-associated protein (GAB2), has been shown to provide a 1.27–1.51 increased odds of developing LOAD for rs7101429 major allele carriers, in case-control analysis. GAB2 is expressed across the brain throughout life, and its role in LOAD pathology is well understood. Recent studies have begun to examine the effect of genetic variation in the GAB2 gene on differences in the brain. However, the effect of GAB2 on the young adult brain has yet to be considered. Here we found a significant association between the GAB2 gene and morphological brain differences in 755 young adult twins (469 females) (M = 23.1, SD = 3.1 years), using a gene-based test with principal components regression (PCReg). Detectable differences in brain morphology are therefore associated with variation in the GAB2 gene, even in young adults, long before the typical age of onset of Alzheimer's disease.
A couple of FeAl alloys containing up to 1.4 at.% Li have been produced by vacuum induction melting. Though previous reports indicated a significant effect of Li on the properties of FeAl, no marked changes with respect to binary FeAl are observed. Specifically, no decrease of the lattice constant and no significant increase in ductility are found by alloying with Li. If at all, there is a slight increase of the lattice constant.
Large, defect-free single-phase samples of the hexagonal C14 NbFe2 and Nb(Fe,Al)2, and the cubic C15 NbCo2 Laves phases have been produced by a modified levitation melting technique. The compressive strength of NbFe2 and NbCo2 has been determined in dependence on the Nb content, that of Nb(Fe,Al)2 in dependence on the Al content. The binary phases did not show either a maximum (defect softening) or minimum (defect hardening) in strength when the Nb content was varied. Instead, for both phases an increase of the compressive strength with increasing Nb content is observed.
Objectives: This study investigates the use of information graphics to display the outputs of health technology assessment (HTA) in the United Kingdom and proposes a more structured approach founded in an analysis of the decision-making requirements of the key stakeholders.
Methods: A scoping review of HTA reports was conducted to investigate current practice in the use of information graphics in HTA literature. A classification framework using dimensions of report section, graphical type, and originating research center was devised and used for a full content analysis of the graphical figures in the fifty most recent reports produced for the UK National Health Service's HTA process.
Results: Our survey shows that graphical tools are used extensively in HTA reports although less frequently than tables. Use of information graphics varies widely between different report sections and tends to follow conventional lines with little evidence of variance from established practice. The largest variance was found between the quantities of graphics used by different research centers responsible for authoring the reports.
Conclusions: HTA makes extensive use of graphics; however, there is little evidence of a systematic or standardized approach, or of much innovation. Significant potential exists to explore the application of information graphics in this field, but there are many research challenges. A contextually based, structured approach to the design of effective information graphics in HTA is proposed as a basis both to investigate the application of existing graphical tools in HTA, and to explore the considerable scope for innovation.