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Direct photometric measurements of the cosmic optical background (COB) provide an important point of comparison to both other measurement methodologies and models of cosmic structure formation, and permit a cosmic consistency test with the potential to reveal additional diffuse sources of emission. The COB has been challenging to measure from Earth due to the difficulty of isolating it from the diffuse light scattered from interplanetary dust in our solar system. We present a measurement of the COB using data taken by the Long-Range Reconnaissance Imager on NASA's New Horizons mission, considering all data acquired to 47 au. We employ a blind methodology where our analysis choices are developed against a subset of the full data set, which is then unblinded. Dark current and other instrumental systematics are accounted for, including a number of sources of scattered light. We fully characterize and remove structured and diffuse astrophysical foregrounds including bright stars, the integrated starlight from faint unresolved sources, and diffuse galactic light. For the full data set, we find the surface brightness of the COB to be λ I λ COB = 21.98 ± 1.23 ( stat . ) ± 1.36 ( cal . ) nW m−2 sr−1. This result supports recent determinations that find a factor of 2-3× more light than expected from the integrated light from galaxies and motivate new diffuse intensity measurements with more capable instruments that can support spectral measurements over the optical and near-IR.

We present the first publicly released catalog of sources obtained from the Hobby-Eberly Telescope Dark Energy Experiment (HETDEX). HETDEX is an integral field spectroscopic survey designed to measure the Hubble expansion parameter and angular diameter distance at 1.88 < z < 3.52 by using the spatial distribution of more than a million Lyα-emitting galaxies over a total target area of 540 deg2. The catalog comes from contiguous fiber spectra coverage of 25 deg2 of sky from 2017 January through 2020 June, where object detection is performed through two complementary detection methods: one designed to search for line emission and the other a search for continuum emission. The HETDEX public release catalog is dominated by emission-line galaxies and includes 51,863 Lyα-emitting galaxy (LAE) identifications and 123,891 [O ii]-emitting galaxies at z < 0.5. Also included in the catalog are 37,916 stars, 5274 low-redshift (z < 0.5) galaxies without emission lines, and 4976 active galactic nuclei. The catalog provides sky coordinates, redshifts, line identifications, classification information, line fluxes, [O ii] and Lyα line luminosities where applicable, and spectra for all identified sources processed by the HETDEX detection pipeline. Extensive testing demonstrates that HETDEX redshifts agree to within Δz < 0.02, 96.1% of the time to those in external spectroscopic catalogs. We measure the photometric counterpart fraction in deep ancillary Hyper Suprime-Cam imaging and find that only 55.5% of the LAE sample has an r-band continuum counterpart down to a limiting magnitude of r ∼ 26.2 mag (AB) indicating that an LAE search of similar sensitivity to HETDEX with photometric preselection would miss nearly half of the HETDEX LAE catalog sample. Data access and details about the catalog can be found online at http://hetdex.org/. A copy of the catalogs presented in this work (Version 3.2) is available to download at Zenodo doi:10.5281/zenodo.7448504.

Despite previous reports on European growing seasons lengthening due to global warming, evidence shows that this trend has been reversing in the past decade due to increased transpiration needs. To asses this, we used an innovative method along with space-based observations to determine the timing of greening and dormancy and then to determine existing trends of them and causes. Early greening still occurs, albeit at slower rates than before. However, a recent (2011–2020) shift in the timing of dormancy has caused the season length to decrease back to 1980s levels. This shortening of season length is attributed primarily to higher atmospheric water demand in summer that suppresses transpiration even for soil moisture levels as of previous years. Transpiration suppression implies that vegetation is unable to meet the high transpiration needs. Our results have implications for future management of European ecosystems (e.g., net carbon balance and water and energy exchange with atmosphere) in a warmer world.

Knowledge on biodiversity is fundamental for conservation strategies. The Brazilian Pampa region, located in subtropical southern Brazil, is neglected in terms of conservation, and knowledge of its biodiversity is fragmented. We aim to answer the question: how many, and which, species occur in the Brazilian Pampa? In a collaborative effort, we built species lists for plants, animals, bacteria, and fungi that occur in the Brazilian Pampa. We included information on distribution patterns, main habitat types, and conservation status. Our study resulted in referenced lists totaling 12,503 species (12,854 taxa, when considering infraspecific taxonomic categories [or units]). Vascular plants amount to 3,642 species (including 165 Pteridophytes), while algae have 2,046 species (2,378 taxa) and bryophytes 316 species (318 taxa). Fungi (incl. lichenized fungi) contains 1,141 species (1,144 taxa). Animals total 5,358 species (5,372 taxa). Among the latter, vertebrates comprise 1,136 species, while invertebrates are represented by 4,222 species. Our data indicate that, according to current knowledge, the Pampa holds approximately 9% of the Brazilian biodiversity in an area of little more than 2% of Brazil’s total land. The proportion of species restricted to the Brazilian Pampa is low (with few groups as exceptions), as it is part of a larger grassland ecoregion and in a transitional climatic setting. Our study yielded considerably higher species numbers than previously known for many species groups; for some, it provides the first published compilation. Further efforts are needed to increase knowledge in the Pampa and other regions of Brazil. Considering the strategic importance of biodiversity and its conservation, appropriate government policies are needed to fund studies on biodiversity, create accessible and constantly updated biodiversity databases, and consider biodiversity in school curricula and other outreach activities.

BackgroundLarge-scale trials of multidomain interventions show that modifying lifestyle and psychological risk factors can slow cognitive decline. We aim to determine if a lower intensity, personally tailored secondary dementia prevention programme for older people with subjective or mild objective memory decline, informed by behaviour change theory, reduces cognitive decline over 2 years.MethodsA multi-site, single-blind randomised controlled trial recruiting 704 older adults at high dementia risk due to mild cognitive impairment (MCI) or subjective cognitive decline (SCD). Participants are randomised using 1:1 allocation ratio to the APPLE Tree intervention versus control arm (dementia prevention information), stratified by site. The intervention explores and implements strategies to promote healthy lifestyle, increase pleasurable activities and social connections and improve long-term condition self-management. Two facilitators trained and supervised by a clinical psychologist deliver ten, 1-h group video call sessions over 6 months (approximately every fortnight), video-call 'tea breaks' (less structured, facilitated social sessions) in intervening weeks and individual goal-setting phone calls every 2 weeks. From 6 to 12 months, participants meet monthly for 'tea breaks', with those not attending receiving monthly goal-setting phone calls. Participants receive a food delivery, pedometer and website access to cognitive training and information about lifestyle modification. Follow-ups for all outcome measures are at 12 and 24 months. The primary outcome is cognition (Neuropsychological Test Battery (NTB) score) at 24 months. Secondary outcomes are quality of life, cost per quality-adjusted life year (QALY) and wellbeing and lifestyle factors the intervention targets (diet, vascular risk, body weight, activity, sleep, anxiety, depression, social networks and loneliness, alcohol intake and smoking). Participants from purposively selected sites participate in qualitative process evaluation interviews, which will be analysed using thematic analytic methods.DiscussionIf effective, the intervention design, involving remote delivery and non-clinical facilitators, would facilitate intervention roll-out to older people with memory concerns.Trial registrationISRCTN17325135 . Registration date 27 November 2019.

Gastrointestinal stromal tumors (GIST) are the most common type of soft tissue sarcoma that occur throughout the gastrointestinal tract. Most of these tumors are caused by oncogenic activating mutations in the KIT or PDGFRA genes. The NCCN Guidelines for GIST provide recommendations for the diagnosis, evaluation, treatment, and follow-up of patients with these tumors. These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines, including revised systemic therapy options for unresectable, progressive, or metastatic GIST based on mutational status, and updated recommendations for the management of GIST that develop resistance to specific tyrosine kinase inhibitors.

Soft tissue sarcomas (STS) are rare malignancies of mesenchymal cell origin that display a heterogenous mix of clinical and pathologic characteristics. STS can develop from fat, muscle, nerves, blood vessels, and other connective tissues. The evaluation and treatment of patients with STS requires a multidisciplinary team with demonstrated expertise in the management of these tumors. The complete NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Soft Tissue Sarcoma provide recommendations for the diagnosis, evaluation, and treatment of extremity/superficial trunk/head and neck STS, as well as retroperitoneal/intra-abdominal STS, desmoid tumors, and rhabdomyosarcoma. This portion of the NCCN Guidelines discusses general principles for the diagnosis and treatment of retroperitoneal/intra-abdominal STS, outlines treatment recommendations, and reviews the evidence to support the guidelines recommendations.

Background and objectivesThe Covid-19 pandemic reduced access to social activities and routine health care that are central to dementia prevention. We developed a group-based, video-call, cognitive well-being intervention; and investigated its acceptability and feasibility; exploring through participants' accounts how the intervention was experienced and used in the pandemic context.Research design and methodWe recruited adults aged 60+ years with memory concerns (without dementia). Participants completed baseline assessments and qualitative interviews/focus groups before and after the 10-week intervention. Qualitative interview data and facilitator notes were integrated in a thematic analysis.Results12/17 participants approached completed baseline assessments, attended 100/120 (83.3%) intervention sessions and met 140/170 (82.4%) of goals set. Most had not used video calling before. In the thematic analysis, our overarching theme was social connectedness. Three sub-themes were as follows: Retaining independence and social connectedness: social connectedness could not be at the expense of independence; Adapting social connectedness in the pandemic: participants strived to compensate for previous social connectedness as the pandemic reduced support networks; Managing social connections within and through the intervention: although there were tensions, for example, between sharing of achievements feeling supportive and competitive, participants engaged with various lifestyle changes; social connections supported group attendance and implementation of lifestyle changes.Discussion and implicationsOur intervention was acceptable and feasible to deliver by group video-call. We argue that dementia prevention is both an individual and societal concern. For more vulnerable populations, messages that lifestyle change can help memory should be communicated alongside supportive, relational approaches to enabling lifestyle changes.

Mammalian brains feature exceptionally high levels of non-CpG DNA methylation alongside the canonical form of CpG methylation. Non-CpG methylation plays a critical regulatory role in cognitive function, which is mediated by the binding of MeCP2, the transcriptional regulator that when mutated causes Rett syndrome. However, it is unclear whether the non-CpG neural methylation system is restricted to mammalian species with complex cognitive abilities or has deeper evolutionary origins. To test this, we investigated brain DNA methylation across 12 distantly related animal lineages, revealing that non-CpG methylation is restricted to vertebrates. We discovered that in vertebrates, non-CpG methylation is enriched within a highly conserved set of developmental genes transcriptionally repressed in adult brains, indicating that it demarcates a deeply conserved regulatory program. We also found that the writer of non-CpG methylation, DNMT3A, and the reader, MeCP2, originated at the onset of vertebrates as a result of the ancestral vertebrate whole-genome duplication. Together, we demonstrate how this novel layer of epigenetic information assembled at the root of vertebrates and gained new regulatory roles independent of the ancestral form of the canonical CpG methylation. This suggests that the emergence of non-CpG methylation may have fostered the evolution of sophisticated cognitive abilities found in the vertebrate lineage.

Decades of empirical research have confirmed the prevalence of troublesome situations involving civil legal issues in everyday life. Although these problems can be associated with serious financial and social harm, they rarely involve recourse to lawyers or formal legal institutions. Contemporary scholars and practitioners increasingly integrate this reality into the definition of access to justice. They understand access to justice to be concerned with equality in the ability of individuals to achieve just resolutions to the problems they experience, regardless of whether they pursue formal legal action. To achieve this goal, an emerging international set of best practices calls for access to justice interventions that are proactively targeted to those groups most in need of assistance, linked to other social service providers, aimed at addressing problems early to avoid escalation, and customized to the user’s capabilities. In stark opposition to such an outward-facing, multifaceted approach, the civil justice system is structured to respond only to formal legal claims. We have few auxiliary institutions that provide alternative avenues to resolution and several barriers inhibit individuals’ ability to address civil legal problems. As a result, access to justice, as contemporarily understood, is largely an orphan issue—a social problem for which no institution bears responsibility. In this Article, I propose an agenda of institutional reforms to better align key social institutions with a contemporary, evidence-based understanding of access to justice. These institutional reforms would enhance individuals’ ability to access justice, within or without the courthouse walls.

A series of achiral tricatenar rod-like molecules with a 3,5-disubstitution pattern at one end and a single alkyl chain at the other end of a rod-like azobenzene derived core is reported. Depending on temperature and alkyl chain length, these Y-shaped compounds self-assemble into different types of liquid crystalline (LC) phases, ranging from non-tilted and synclinic tilted hexatic, via non-tilted and anticlinic tilted smectic and bicontinuous cubic LC phases, to a spontaneous mirror symmetry broken isotropic liquid (Iso1[∗]) or a related achiral liquid network phase (Iso1). An additional tilted, but uniaxial smectic phase was observed at the transition between anticlinic and synclinic tilt correlation and was investigated by soft resonant X-ray scattering with respect to possible helix formation. This work provides a new concept for the design of technological interesting azobenzene based LC materials with anticlinic tilted smectic C phases (SmCa) and with azobenzene units organized in the long range or short range helical network structures of bicontinuous cubic and chiral isotropic liquid phases, respectively. Core fluorination removes all lamellar phases, leaving only the cubic phase over wide temperature ranges, even at ambient temperature. This journal is

BackgroundThe AS04-adjuvanted HPV16/18 (AS04-HPV16/18) vaccine provides excellent protection against targeted human papillomavirus (HPV) types and a variable degree of cross-protection against others, including types 6/11/31/33/45. High efficacy against any cervical intraepithelial neoplasia grade 3 or greater (CIN3+; >90%) suggests that lower levels of protection may exist for a wide range of oncogenic HPV types, which is difficult to quantify in individual trials. Pooling individual-level data from two randomized controlled trials, we aimed to evaluate AS04-HPV16/18 vaccine efficacy against incident HPV infections and cervical abnormalities .MethodsData were available from the Costa Rica Vaccine Trial (NCT00128661) and Papilloma Trial Against Cancer in Young Adults trial (NCT00122681), two large-scale, double-blind randomized controlled trials of the AS04-HPV16/18 vaccine. Primary analyses focused on disease-free women with no detectable cervicovaginal HPV at baseline.ResultsA total of 12 550 women were included in our primary analyses (HPV arm = 6271, control arm = 6279). Incidence of 6-month persistent oncogenic and nononcogenic infections, excluding known and accepted protected types 6/11/16/18/31/33/45 (focusing on 34/35/39/40/42/43/44/51/52/53/54/56/58/59/66/68/73/70/74), was statistically significantly lower in the HPV arm than in the control arm (efficacy = 9.9%, 95% confidence interval [CI] = 1.7% to 17.4%). Statistically significant efficacy (P

The refilling of the lunar wake is facilitated by the wake ambipolar electric potential arising from the electron pressure gradient. Incident solar wind protons can be reflected by the lunar crustal magnetic fields and the lunar surface on the dayside and repicked up, entering the lunar wake due to their large gyroradii. This burst of positive charges can cause the lunar wake potential to be reduced by hundreds of volts. We utilize over 7 years of ARTEMIS (Acceleration, Reconnection, Turbulence, and Electrodynamics of the Moons Interaction with the Sun) measurements to systematically investigate how the reflected protons affect the lunar wake potential structure when the Moon is immersed in the solar wind. RPs have a peak occurrence rate of ~20% for downstream distances from the Moon at N × 2πR g and a preference of high occurrence rates and high densities in the direction of the motional electric field of the solar wind. We show that reflected protons in the lunar wake can significantly change the electrostatic ambipolar potentials in the wake, leading in turn to the formation of field-aligned, accelerated electron beams. Our case study also suggests a nonmonotonic field-aligned potential structure in the presence of reflected protons in the wake. Lastly, our results show that when the reflected proton density is larger than ~30% of the local proton density from refilling solar wind protons, the wake potential scales as the logarithmic density of reflected protons, which can be explained by the Boltzmann relation.

"Myxoid glioneuronal tumor, PDGFRA p.K385-mutant" is a recently described tumor entity of the central nervous system with a predilection for origin in the septum pellucidum and a defining dinucleotide mutation at codon 385 of the PDGFRA oncogene replacing lysine with either leucine or isoleucine (p.K385L/I). Clinical outcomes and optimal treatment for this new tumor entity have yet to be defined. Here, we report a comprehensive clinical, radiologic, and histopathologic assessment of eight cases. In addition to its stereotypic location in the septum pellucidum, we identify that this tumor can also occur in the corpus callosum and periventricular white matter of the lateral ventricle. Tumors centered in the septum pellucidum uniformly were associated with obstructive hydrocephalus, whereas tumors centered in the corpus callosum and periventricular white matter did not demonstrate hydrocephalus. While multiple patients were found to have ventricular dissemination or local recurrence/progression, all patients in this series remain alive at last clinical follow-up despite only biopsy or subtotal resection without adjuvant therapy in most cases. Our study further supports "myxoid glioneuronal tumor, PDGFRA p.K385-mutant" as a distinct CNS tumor entity and expands the spectrum of clinicopathologic and radiologic features of this neoplasm.

Introduction: Post-tonsillectomy hemorrhage is a potentially life-threatening, postoperative complication that is commonly encountered in the emergency department (ED).Case Report: Herein, we describe the case of a 22-year-old male who presented to the ED with an active post-tonsillectomy hemorrhage. He rapidly became hypotensive and experienced an episode of syncope. Immediate interventions included intravenous fluids, emergency release blood and nebulized tranexamic acid (TXA). After completion of the nebulized TXA, the patient’s bleeding was controlled.Conclusion: To our knowledge, this is the first case in the emergency medicine literature that describes the use of nebulized TXA in an adult to achieve hemostasis in post-tonsillectomy hemorrhage.

Non-human primate models have been useful in clarifying estradiol's role in cognitive processing. These animal studies indicate estradiol impacts cognitive processes supported by regions within dorsolateral prefrontal cortex (DLPFC). Although human functional neuroimaging studies have begun to find similar relationships between estradiol in women for some forms of 'cold' cognitive control, to date no studies have examined the relationship between estradiol and DLPFC function in the context of active attempts to regulate one's emotions. Here, we asked whether peripheral 17-beta estradiol levels in adolescent girls in different pubertal developmental stages (age = 14.9 years ± 1.74) were related to engagement of DLPFC regions during the use of a cognitive strategy for regulating emotion known as reappraisal using functional Magnetic Resonance Imaging. Findings indicated that higher estradiol levels predicted greater DLPFC activity during the down-regulation of negative emotion using reappraisal. This is the first report of an association between estradiol level and DLPFC activity during cognitive reappraisal of negative emotion. The study suggests a possibility that estradiol might positively contribute to regulatory function of a cortical system important for emotional experiences.

Non-human primate models have been useful in clarifying estradiol's role in cognitive processing. These animal studies indicate estradiol impacts cognitive processes supported by regions within dorsolateral prefrontal cortex (DLPFC). Although human functional neuroimaging studies have begun to find similar relationships between estradiol in women for some forms of 'cold' cognitive control, to date no studies have examined the relationship between estradiol and DLPFC function in the context of active attempts to regulate one's emotions. Here, we asked whether peripheral 17-beta estradiol levels in adolescent girls in different pubertal developmental stages (age = 14.9 years ± 1.74) were related to engagement of DLPFC regions during the use of a cognitive strategy for regulating emotion known as reappraisal using functional Magnetic Resonance Imaging. Findings indicated that higher estradiol levels predicted greater DLPFC activity during the down-regulation of negative emotion using reappraisal. This is the first report of an association between estradiol level and DLPFC activity during cognitive reappraisal of negative emotion. The study suggests a possibility that estradiol might positively contribute to regulatory function of a cortical system important for emotional experiences.

Interferon regulatory factor 2 binding protein-like (IRF2BPL) encodes a member of the IRF2BP family of transcriptional regulators. Currently the biological function of this gene is obscure, and the gene has not been associated with a Mendelian disease. Here we describe seven individuals who carry damaging heterozygous variants in IRF2BPL and are affected with neurological symptoms. Five individuals who carry IRF2BPL nonsense variants resulting in a premature stop codon display severe neurodevelopmental regression, hypotonia, progressive ataxia, seizures, and a lack of coordination. Two additional individuals, both with missense variants, display global developmental delay and seizures and a relatively milder phenotype than those with nonsense alleles. The IRF2BPL bioinformatics signature based on population genomics is consistent with a gene that is intolerant to variation. We show that the fruit-fly IRF2BPL ortholog, called pits (protein interacting with Ttk69 and Sin3A), is broadly detected, including in the nervous system. Complete loss of pits is lethal early in development, whereas partial knockdown with RNA interference in neurons leads to neurodegeneration, revealing a requirement for this gene in proper neuronal function and maintenance. The identified IRF2BPL nonsense variants behave as severe loss-of-function alleles in this model organism, and ectopic expression of the missense variants leads to a range of phenotypes. Taken together, our results show that IRF2BPL and pits are required in the nervous system in humans and flies, and their loss leads to a range of neurological phenotypes in both species.

The rapid diagnosis and treatment of tuberculosis (TB) is necessary to prevent the spread of infecti onto others and reduce morbidity and mortality. Atypical presentations are not often considered in the differential. This patient presented with fever and abdominal pain. Computed tomography of the abdomen and pelvis showed small bowel obstruction, initially attributed to the patient’s Crohn’s disease. Chest radiograph showed diffuse interstitial lung disease, consistent with his diagnosis of sarcoidosis. He had multiple recent negative tuberculin skin tests documented. After being admitted to the surgical service and started on antibiotics, the diagnosis of abdominal TB was discovered following surgical exploration and tissue sampling.

The cosmic optical background is an important observable that constrains energy production in stars and more exotic physical processes in the universe, and provides a crucial cosmological benchmark against which to judge theories of structure formation. Measurement of the absolute brightness of this background is complicated by local foregrounds like the Earths atmosphere and sunlight reflected from local interplanetary dust, and large discrepancies in the inferred brightness of the optical background have resulted. Observations from probes far from the Earth are not affected by these bright foregrounds. Here we analyse the data from the Long Range Reconnaissance Imager (LORRI) instrument on NASAs New Horizons mission acquired during cruise phase outside the orbit of Jupiter, and find a statistical upper limit on the optical backgrounds brightness similar to the integrated light from galaxies. We conclude that a carefully performed survey with LORRI could yield uncertainties comparable to those from galaxy counting measurements.

BackgroundBRCA1 and, more commonly, BRCA2 mutations are associated with increased risk of male breast cancer (MBC). However, only a paucity of data exists on the pathology of breast cancers (BCs) in men with BRCA1/2 mutations. Using the largest available dataset, we determined whether MBCs arising in BRCA1/2 mutation carriers display specific pathologic features and whether these features differ from those of BRCA1/2 female BCs (FBCs).MethodsWe characterised the pathologic features of 419 BRCA1/2 MBCs and, using logistic regression analysis, contrasted those with data from 9675 BRCA1/2 FBCs and with population-based data from 6351 MBCs in the Surveillance, Epidemiology, and End Results (SEER) database.ResultsAmong BRCA2 MBCs, grade significantly decreased with increasing age at diagnosis (P = 0.005). Compared with BRCA2 FBCs, BRCA2 MBCs were of significantly higher stage (P for trend = 2 × 10(-5)) and higher grade (P for trend = 0.005) and were more likely to be oestrogen receptor-positive [odds ratio (OR) 10.59; 95 % confidence interval (CI) 5.15-21.80] and progesterone receptor-positive (OR 5.04; 95 % CI 3.17-8.04). With the exception of grade, similar patterns of associations emerged when we compared BRCA1 MBCs and FBCs. BRCA2 MBCs also presented with higher grade than MBCs from the SEER database (P for trend = 4 × 10(-12)).ConclusionsOn the basis of the largest series analysed to date, our results show that BRCA1/2 MBCs display distinct pathologic characteristics compared with BRCA1/2 FBCs, and we identified a specific BRCA2-associated MBC phenotype characterised by a variable suggesting greater biological aggressiveness (i.e., high histologic grade). These findings could lead to the development of gender-specific risk prediction models and guide clinical strategies appropriate for MBC management.

Patients with schizophrenia (SZ) previously demonstrated specific deficits in an executive function known as goal maintenance, associated with reduced middle frontal gyrus (MFG) activity. This study aimed to validate a new tool-the Dot Pattern Expectancy (DPX) task-developed to facilitate multisite imaging studies of goal maintenance deficits in SZ or other disorders. Additionally, it sought to arrive at recommendations for scan length for future studies using the DPX. Forty-seven SZ and 56 healthy controls (HC) performed the DPX in 3-Tesla functional magnetic resonance imaging (fMRI) scanners at 5 sites. Group differences in DPX-related activity were examined with whole brain voxelwise analyses. SZs showed the hypothesized specific performance deficits with as little as 1 block of data. Reduced activity in SZ compared with HC was observed in bilateral frontal pole/MFG, as well as left posterior parietal lobe. Efficiency analyses found significant group differences in activity using 18 minutes of scan data but not 12 minutes. Several behavioral and imaging findings from the goal maintenance literature were robustly replicated despite the use of different scanners at different sites. We did not replicate a previous correlation with disorganization symptoms among patients. Results were consistent with an executive/attention network dysfunction in the higher levels of a cascading executive system responsible for goal maintenance. Finally, efficiency analyses found that 18 minutes of scanning during the DPX task is sufficient to detect group differences with a similar sample size.

BackgroundBRCA1 and, more commonly, BRCA2 mutations are associated with increased risk of male breast cancer (MBC). However, only a paucity of data exists on the pathology of breast cancers (BCs) in men with BRCA1/2 mutations. Using the largest available dataset, we determined whether MBCs arising in BRCA1/2 mutation carriers display specific pathologic features and whether these features differ from those of BRCA1/2 female BCs (FBCs).MethodsWe characterised the pathologic features of 419 BRCA1/2 MBCs and, using logistic regression analysis, contrasted those with data from 9675 BRCA1/2 FBCs and with population-based data from 6351 MBCs in the Surveillance, Epidemiology, and End Results (SEER) database.ResultsAmong BRCA2 MBCs, grade significantly decreased with increasing age at diagnosis (P = 0.005). Compared with BRCA2 FBCs, BRCA2 MBCs were of significantly higher stage (P for trend = 2 × 10(-5)) and higher grade (P for trend = 0.005) and were more likely to be oestrogen receptor-positive [odds ratio (OR) 10.59; 95 % confidence interval (CI) 5.15-21.80] and progesterone receptor-positive (OR 5.04; 95 % CI 3.17-8.04). With the exception of grade, similar patterns of associations emerged when we compared BRCA1 MBCs and FBCs. BRCA2 MBCs also presented with higher grade than MBCs from the SEER database (P for trend = 4 × 10(-12)).ConclusionsOn the basis of the largest series analysed to date, our results show that BRCA1/2 MBCs display distinct pathologic characteristics compared with BRCA1/2 FBCs, and we identified a specific BRCA2-associated MBC phenotype characterised by a variable suggesting greater biological aggressiveness (i.e., high histologic grade). These findings could lead to the development of gender-specific risk prediction models and guide clinical strategies appropriate for MBC management.

Host specialization by pathogens requires a repertoire of virulence factors as well as fine-tuned regulation of gene expression. The fungal wheat pathogen Zymoseptoria tritici (synonym Mycosphaerella graminicola) is a powerful model system for the discovery of genetic elements that underlie virulence and host specialization. We transcriptionally profiled the early stages of Z. tritici infection of a compatible host (wheat) and a noncompatible host (Brachypodium distachyon). The results revealed infection regulatory programs common to both hosts and genes with striking wheat-specific expression, with many of the latter showing sequence signatures of positive selection along the Z. tritici lineage. Genes specifically regulated during infection of wheat populated two large clusters of coregulated genes that may represent candidate pathogenicity islands. On evolutionarily labile, repeat-rich accessory chromosomes (ACs), we identified hundreds of highly expressed genes with signatures of evolutionary constraint and putative biological function. Phylogenetic analyses suggested that gene duplication events on these ACs were rare and largely preceded the diversification of Zymoseptoria species. Together, our data highlight the likely relevance for fungal growth and virulence of hundreds of Z. tritici genes, deepening the annotation and functional inference of the genes of this model pathogen.

Host specialization by pathogens requires a repertoire of virulence factors as well as fine-tuned regulation of gene expression. The fungal wheat pathogen Zymoseptoria tritici (synonym Mycosphaerella graminicola) is a powerful model system for the discovery of genetic elements that underlie virulence and host specialization. We transcriptionally profiled the early stages of Z. tritici infection of a compatible host (wheat) and a noncompatible host (Brachypodium distachyon). The results revealed infection regulatory programs common to both hosts and genes with striking wheat-specific expression, with many of the latter showing sequence signatures of positive selection along the Z. tritici lineage. Genes specifically regulated during infection of wheat populated two large clusters of coregulated genes that may represent candidate pathogenicity islands. On evolutionarily labile, repeat-rich accessory chromosomes (ACs), we identified hundreds of highly expressed genes with signatures of evolutionary constraint and putative biological function. Phylogenetic analyses suggested that gene duplication events on these ACs were rare and largely preceded the diversification of Zymoseptoria species. Together, our data highlight the likely relevance for fungal growth and virulence of hundreds of Z. tritici genes, deepening the annotation and functional inference of the genes of this model pathogen.