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A widely cited but poorly supported idea in the couples therapy field is that the average couple waits six years before starting therapy for serious relationship problems. This figure is often accompanied by the notion that many couples come "too late" and have poor prospects for recovery. This is the first large-sample study on the delay between the onset of serious marital problems and entry into couples therapy (N = 270) and individual therapy (N = 101) for relationship problems. We found an average interval of 2.68 years from onset of problems and entering couples therapy, with the great majority of couples entering therapy within two years. Findings were similar for seeking individual therapy for relationship problems. The main clinical implication is that therapists have little reason to be pessimistic about the majority of couples waiting so long before starting therapy that their problems are not resolvable.

Guided by the Stages of Change (SOC) model, we explored relationship-repair behaviors among those thinking about divorce, employing a recent national longitudinal survey of married individuals (N = 745). Person-centered analyses explored whether there were distinct typologies of relationship-repair behaviors. We found four distinct classes: Intense Seekers (6%), who engaged at high levels of all kinds of repair behaviors, including professional services; Moderate-fading Seekers (14%), who engaged in moderate levels of various repair behaviors, including professional services, but did not sustain that behavior over a year; and Minimal-private Seekers (42%) and Private-sustained Seekers (38%), who eschewed professional services and engaged in low-to-moderate personal and private repair behaviors. We discuss possible applications of the SOC model to the divorce decision-making process and conclude with implications for practice, including the need to allocate greater attention to personal and self-help interventions that match the way most people try to repair their relationships.

Reducing fracture risk is the objective of osteoporosis treatment. Bone-forming osteoporosis drugs increase bone mass, restore bone microarchitecture, and reduce fracture risk more effectively than oral bisphosphonates, providing strong justification for the use of these agents as the initial therapy or after anti-remodeling agents in patients at very high risk of fracture. At the end of a 12-to-24-month course of osteoanabolic therapy, transitioning to a potent anti-remodeling agent maintains and enhances the treatment benefit. This review describes the clinical applications of osteoanabolic therapy for osteoporosis.

Discernment counseling is designed to help couples considering divorce arrive at a greater sense of clarity and confidence in their decision making about the future of their marriage. Possible outcomes include making no change to the marriage, divorcing, or attempting reconciliation through couples therapy. To date, no research has been done on whether or not discernment counseling helps couples who decide to divorce with their post‐divorce family life (i.e., coparenting). We surveyed 11 people (from male–female couples) and conducted in‐depth interviews with eight who had undergone discernment counseling and subsequently divorced to see what impact discernment counseling had on their post‐divorce coparenting relationship. We analyzed the data from a phenomenological perspective. Respondents described their discernment counseling experience as helpful for achieving clarity and honesty in the divorce decision‐making process, they shared their appreciation for the structure of the intervention, and indicated that it led to a greater coparental cooperation post‐divorce.

The transcriptome and phosphoproteome of the filamentous fungus Aspergillus nidulans was monitored after cell wall stress. Over 1800 genes and 700 phosphorylation sites showed dynamic expression and occupancy, respectively. These data guided selection of kinase deletion strains for testing for cell-wall related phenotypes. Kinase-substrate analysis revealed possible connections between CWIS, SIN, HOG, and calcium pathways. Fungi exposed to wall stress experience an increase in septation formation, which may function as a biological defense mechanism., Graphical Abstract Highlights • Dynamic transcriptomic and phosphoproteomic study of response to cell-wall stress. • MARS model identifies significantly dynamic gene expression and phosphorylation. • Septation formation increases during cell-wall stress (via micafungin exposure). • Cell wall phenotype assays identified 8 putative CWIS related kinases., The fungal cell-wall integrity signaling (CWIS) pathway regulates cellular response to environmental stress to enable wall repair and resumption of normal growth. This complex, interconnected, pathway has been only partially characterized in filamentous fungi. To better understand the dynamic cellular response to wall perturbation, a β-glucan synthase inhibitor (micafungin) was added to a growing A. nidulans shake-flask culture. From this flask, transcriptomic and phosphoproteomic data were acquired over 10 and 120 min, respectively. To differentiate statistically-significant dynamic behavior from noise, a multivariate adaptive regression splines (MARS) model was applied to both data sets. Over 1800 genes were dynamically expressed and over 700 phosphorylation sites had changing phosphorylation levels upon micafungin exposure. Twelve kinases had altered phosphorylation and phenotypic profiling of all non-essential kinase deletion mutants revealed putative connections between PrkA, Hk-8–4, and Stk19 and the CWIS pathway. Our collective data implicate actin regulation, endocytosis, and septum formation as critical cellular processes responding to activation of the CWIS pathway, and connections between CWIS and calcium, HOG, and SIN signaling pathways.

Cytokinesis, as the final step of cell division, plays an important role in fungal growth and proliferation. In the filamentous fungus Aspergillus nidulans, defective cytokinesis is able to induce abnormal multinuclear or nonnucleated cells and then result in reduced hyphal growth and abolished sporulation. Previous studies have reported that a conserved contractile actin ring (CAR) protein complex and the septation initiation network (SIN) signaling kinase cascade are required for cytokinesis and septation; however, little is known about the role(s) of scaffold proteins involved in these two important cellular processes. In this study, we show that a septum-localized scaffold protein paxillin B (PaxB) is essential for cytokinesis/septation in A. nidulans. The septation defects observed in a paxB deletion strain resemble those caused by the absence of another identified scaffold protein, α-actinin (AcnA). Deletion of α-actinin (AcnA) leads to undetectable PaxB at the septation site, whereas deletion of paxB does not affect the localization of α-actinin at septa. However, deletion of either α-actinin (acnA) or paxB causes the actin ring to disappear at septation sites during cytokinesis. Notably, overexpression of α-actinin acnA partially rescues the septum defects of the paxB mutant but not vice versa, suggesting AcnA may play a dominant role over that of PaxB for cytokinesis and septation. In addition, PaxB and α-actinin affect the septal dynamic localization of MobA, a conserved component of the SIN pathway, suggesting they may affect the SIN protein complex function at septa. Protein pull-down assays combined with liquid chromatography–mass spectrometry identification indicate that α-actinin AcnA and PaxB likely do not directly interact, but presumably belong to an actin cytoskeleton protein network that is required for the assembly and contraction of the CAR. Taken together, findings in this study provide novel insights into the roles of conserved scaffold proteins during fungal septation in A. nidulans.

This study examined the prevalence of relationship undermining statements by psychotherapists as reported by clients in individual therapy who presented with relationship problems, and whether these statements were associated with worse outcomes for client relationships. Participants (n = 101) reported on recollections of whether their therapist had suggested that their partner would never change, had a diagnosable personality/mental health disorder, had negative motives, that the relationship was doomed from the start or beyond repair now, or that divorce/breakup was their best option. Findings showed high prevalence of these undermining statements and associations with poorer relationship outcomes and shorter duration of therapy. We discuss potential explanations for this phenomenon and offer implications for the training of therapists who treat individual clients with relationship problems.对婚姻和其他亲密关系问题的关注是个体心理治疗中常见的表现问题 (FARRELL, CAMPLAIR,MCCULLOUGH, 1987; 格林斯潘和库利什, 1985年; NAKASH, COHEN,NAGAR, 2018; 洋纺, 2018; ROSEN, ADLER,TIET, 2013)。然而, 个体治疗师缺乏如何处理这些关系问题的培训(GURMANBURTON, 2014)。多年来, 当个体治疗师接受他们(个人)客户对伴侣的观点或建议他们从未见过的配偶的诊断时, 一些伴侣治疗师表达了可能会对夫妻关系造成损害的担忧(DOHERTY, 2002; FOX,1968; HURVITZ, 1967)。这样的言论可能会破坏来访者之间的关系。然而, 当来访者在关系问题上寻求帮助时, 人们对个别治疗师的实际做法知之甚少。我们介绍了一项针对在个人治疗中出现关系问题的个人的试点研究结果。我们特别感兴趣的是, 正如来访者回忆的那样, 治疗师说出被认为是有损关系的陈述的情况是否普遍存在, 以及这些陈述是否与治疗结果有关。.

Septation in filamentous fungi is a normal part of development, which involves the formation of cross-hyphal bulkheads, typically containing pores, allowing cytoplasmic streaming between compartments. Based on previous findings regarding septa and cell wall stress, we hypothesized that septa are critical for survival during cell wall stress. To test this hypothesis, we used known Aspergillus nidulans septation-deficient mutants (Δ

In this work, we estimate how much bulk viscosity driven by Urca processes is likely to affect the gravitational wave signal of a neutron star coalescence. In the late inspiral, we show that bulk viscosity affects the binding energy at fourth post-Newtonian (PN) order. Even though this effect is enhanced by the square of the gravitational compactness, the coefficient of bulk viscosity is likely too small to lead to observable effects in the waveform during the late inspiral, when only considering the orbital motion itself. In the post-merger, however, the characteristic time-scales and spatial scales are different, potentially leading to the opposite conclusion. We post-process data from a state-of-the-art equal-mass binary neutron star merger simulation to estimate the effects of bulk viscosity (which was not included in the simulation itself). In that scenario, we find that bulk viscosity can reach high values in regions of the merger. We compute several estimates of how much it might directly affect the global dynamics of the considered merger scenario, and find that it could become significant. Even larger effects could arise in different merger scenarios or in simulations that include non-linear effects. This assessment is reinforced by a quantitative comparison with relativistic heavy-ion collisions where such effects have been explored extensively., Comment: 12 pages, 6 figures

Black yeasts are polyextremotolerant fungi that contain high amounts of melanin in their cell wall and maintain a primarily yeast form. These fungi grow in xeric, nutrient deplete environments which implies that they require highly flexible metabolisms and have been suggested to contain the ability to form lichen-like mutualisms with nearby algae and bacteria. However, the exact ecological niche and interactions between these fungi and their surrounding community is not well understood. We have isolated two novel black yeasts from the genusExophialathat were recovered from dryland biological soil crusts. Despite notable differences in colony and cellular morphology, both fungi appear to be members of the same species, which has been namedExophiala viscosa (i.e., E. viscosaJF 03-3 Goopyand E. viscosaJF 03-4F Slimy). A combination of whole genome sequencing, phenotypic experiments, and melanin regulation experiments have been performed on these isolates to fully characterize these fungi and help decipher their fundamental niches within the biological soil crust consortium. Our results reveal thatE. viscosais capable of utilizing a wide variety of carbon and nitrogen sources potentially derived from symbiotic microbes, can withstand many forms of abiotic stresses, and excrete melanin that can potentially provide UV resistance to the biological soil crust community. Besides the identification of a novel species within the genusExophiala, our study also provides new insight into the regulation of melanin production in polyextremotolerant fungi.

We calculate the nonzero-temperature correction to the beta equilibrium condition in nuclear matter under neutron star merger conditions, in the temperature range $1\,$MeV$ < T \lesssim 5\,$MeV. We improve on previous work by using a consistent description of nuclear matter based on the IUF and SFHo relativistic mean field models. This includes using relativistic dispersion relations for the nucleons, which we show is essential in these models. We find that the nonzero-temperature correction can be of order $10$ to $20\,$MeV, and plays an important role in the correct calculation of Urca rates, which can be wrong by factors of $10$ or more if it is neglected., v2: version published in Universe, minor changes in nomenclature, 20 pages, 14 figures

Diabetic foot complications are increasingly burdensome for patients, clinicians, and society. Development of innovative therapies to support good quality basic care is a priority among those with an interest in this area. One of these involves scanning and printing tissues to match and conform to a defect (so-called 3D printing).A single-arm pilot study of ten consecutive patients with a history of a chronic diabetic foot ulcer (DFU), treated with autologous minimally manipulated homologous adipose tissue (AMHAT), dispensed by a specialized 3D bioprinter, Dr. INVIVO, was performed. Patients with nonhealing DFUs present for more than 4 weeks and refractory to standard-of-care therapies were included. Wounds were treated with a single application of AMHAT, and then followed up weekly for up to 12 weeks, or until the wounds healed. The primary outcome measure was complete epithelialization of the wound up to 12 weeks after the treatment. Secondary outcome measures included wound size and/or volume reduction, assessment of ulcer grade, and time to closure.Five wounds were healed by 5 weeks and one at 8 weeks. The mean percent area reduction at 12 weeks was 78.3% (SD: 33.23). Complete closure was achieved in 60% of wounds. The mean time to closure in these wounds was 49.1 days (95% CI, 29.9-68.3). No adverse events were reported.Single treatment of bioprinted AMHAT appears to be a safe and potentially effective treatment modality for patients with chronic DFUs. Further studies are warranted to explore the full potential of 3D bioprinting for tissue repair in this high-risk population.

Researchers have long treated marital separation as a linear transition that inevitably leads to divorce. Popular sources suggest that some couples separate without clarity about how the separation will end, often to assess whether to divorce or stay married. However, to date, we could not locate any empirical research on this kind of ambiguous separation. With a sample of 20 currently separated persons from around the United States, this study employed a hermeneutic phenomenological design to inquire about the experience of separating from one's spouse when the separation was initiated without clarity about how it would end. Six essential themes emerged: (a) our relationship feels ambiguous, (b) separation is a private experience, (c) separation is a lonely experience, (d) benefits to separating, (e) separation is not sustainable, and (f) the outcome is unclear. The article concludes with a discussion of and implications for the study findings.

The genus Orthotrichia was last reviewed in 1961 by Kingsolver & Ross, but drawings of the males were primarily restricted to ventral views, and females of only one species was included. The six species comprising the genus in North America are all known from Florida and extensive collecting throughout the state has allowed us to associate the females with the males. With this paper, we provide new drawings and keys of the males and females of the Orthotrichia in Florida, which should be applicable to all of North America, and describe the females of O. curta Kingsolver & Ross, O. dentata Kingsolver & Ross, and O. instabilis Denning.

Protein concentration determination is a necessary in-process control for the downstream operations within biomanufacturing. As production transitions from batch mode to an integrated continuous bioprocess paradigm, there is a growing need to move protein concentration quantitation from off-line to in-line analysis. One solution to fulfill this process analytical technology need is an in-line index of refraction (IoR) sensor to measure protein concentration in real time. Here the performance of an IoR sensor is evaluated through a series of experiments to assess linear response, buffer matrix effects, dynamic range, sensor-to-sensor variability, and the limits of detection and quantitation. The performance of the sensor was also tested in two bioprocessing scenarios, ultrafiltration and capture chromatography. The implementation of this in-line IoR sensor for real-time protein concentration analysis and monitoring has the potential to improve continuous bioprocess manufacturing.

Fungal cell wall receptors relay messages about the state of the cell wall to the nucleus through the Cell Wall Integrity Signaling (CWIS) pathway. The ultimate role of the CWIS pathway is to coordinate repair of cell wall damage and to restore normal hyphal growth. Echinocandins such as micafungin represent a class of antifungals that trigger cell wall damage by affecting synthesis of β-glucans, filamentous fungi’s response to these antifungals are fundamentally unknown. To obtain a better understanding of the dynamics of the CWIS response and its multiple effects, we have coupled dynamic transcriptome analysis with morphological studies of Aspergillus nidulans hyphae responding to micafungin. Our results reveal that expression of the master regulator of asexual development, BrlA, is induced by micafungin exposure. Further study showed that micafungin elicits microcycle conidiation in a BrlA-dependent manner, and that this response is abolished in the absence of MpkA. Our results suggest that microcycle conidiation may be a general response to cell wall perturbation which in some cases would enable fungi to tolerate or survive otherwise lethal damage.

We review topics in searches for axion-like-particles (ALPs), covering material that is complementary to other recent reviews. The first half of our review covers ALPs in the extreme environments of neutron star cores, the magnetospheres of highly magnetized neutron stars (magnetars), and in neutron star mergers. The focus is on possible signals of ALPs in the photon spectrum of neutron stars and gravitational wave/electromagnetic signals from neutron star mergers. We then review recent developments in laboratory-produced ALP searches, focusing mainly on accelerator-based facilities including beam-dump type experiments and collider experiments. We provide a general-purpose discussion of the ALP search pipeline from production to detection, in steps, and our discussion is straightforwardly applicable to most beam-dump type and reactor experiments. We end with a selective look at the rapidly developing field of ultralight dark matter, specifically the formation of Bose-Einstein Condensates (BECs). We review the properties of BECs of ultralight dark matter and bridge these properties with developments in numerical simulations, and ultimately with their impact on experimental searches., Invited review, submitted to IJMPD. 58 pages, 11 figures. Comments welcome

Quiescent hard X-ray and soft gamma-ray emission from neutron stars constitute a promising frontier to explore axion-like-particles (ALPs). ALP production in the core peaks at energies of a few keV to a few hundreds of keV; subsequently, the ALPs escape and convert to photons in the magnetosphere. The emissivity goes as $\sim T^6$ while the conversion probability is enhanced for large magnetic fields, making magnetars, with their high core temperatures and strong magnetic fields, ideal targets for probing ALPs. We compute the energy spectrum of photons resulting from conversion of ALPs in the magnetosphere and then compare it against hard X-ray data from NuSTAR, INTEGRAL, and XMM-Newton, for a set of eight magnetars for which such data exists. Upper limits are placed on the product of the ALP-nucleon and ALP-photon couplings. For the production in the core, we perform a calculation of the ALP emissivity in degenerate nuclear matter modeled by a relativistic mean field theory. The reduction of the emissivity due to improvements to the one-pion exchange approximation is incorporated, as is the suppression of the emissivity due to proton superfluidity in the neutron star core. A range of core temperatures is considered, corresponding to different models of the steady heat transfer from the core to the stellar surface. For the subsequent conversion, we solve the coupled differential equations mixing ALPs and photons in the magnetosphere. The conversion occurs due to a competition between the dipolar magnetic field and the photon refractive index induced by the external magnetic field. Semi-analytic expressions are provided alongside the full numerical results. We also present an analysis of the uncertainty on the axion limits we derive due to the uncertainties in the magnetar masses, nuclear matter equation of state, and the proton superfluid critical temperature., v1: 44 pages, 15 figures. Comments welcome v2: Updated version with uncertainty bands on ALP couplings coming from different choices of the nuclear equation of state, the mass of the magnetar, and the model of proton singlet superfluidity. Calculation of n+p-->n+p+a clarified. Version matches that published in JCAP

Due to their unique set of multimessenger signals, neutron star mergers have emerged as a novel environment for studies of new physics beyond the Standard Model (SM). As a case study, we consider the simplest extension of the SM scalar sector involving a light CP-even scalar singlet $S$ mixing with the SM Higgs boson. These $S$ particles can be produced abundantly in neutron star mergers via the nucleon bremsstrahlung process. We show that the $S$ particles may either be trapped in or stream freely out of the merger remnant, depending on the $S$ mass, its mixing with the SM Higgs boson, and the temperature and baryon density in the merger. In the free-streaming region, the scalar $S$ will provide an extra channel to cool down the merger remnant, with cooling timescales as small as ${\cal O}$(ms). On the other hand, in the trapped region, the Bose gas of $S$ particles could contribute a larger thermal conductivity than the trapped neutrinos in some parts of the parameter space, thus leading to faster thermal equilibration than expected. Therefore, future observations of the early postmerger phase of a neutron star merger could effectively probe a unique range of the $S$ parameter space, largely complementary to the existing and future laboratory and supernova limits. In view of these results, we hope the merger simulation community will be motivated to implement the effects of light CP-even scalars into their simulations in both the free-streaming and trapped regimes., Comment: 44 pages, 10 figures v2: Matches version to be published in JCAP. Added a discussion of the Boltzmann suppression of the emissivity (fig 5) that occurs for scalar particles with m_S >> T. Added some material on the role of pions

Fungi critically impact the health and function of global ecosystems and economies. In Canada, fungal researchers often work within silos defined by subdiscipline and institutional type, complicating the collaborations necessary to understand the impacts fungi have on the environment, economy, and plant and animal health. Here, we announce the establishment of the Canadian Fungal Research Network (CanFunNet, https://fungalresearch.ca ), whose mission is to strengthen and promote fungal research in Canada by facilitating dialogue among scientists. We summarize the challenges and opportunities for Canadian fungal research that were discussed at CanFunNet’s inaugural meeting in 2019, and identify 4 priorities for our community: (i) increasing collaboration among scientists, (ii) studying diversity in the context of ecological disturbance, (iii) preserving culture collections in the absence of sustained funding, and (iv) leveraging diverse expertise to attract trainees. We have gathered additional information to support our recommendations, including a survey identifying underrepresentation of fungal-related courses at Canadian universities, a list of Canadian fungaria and culture collections, and a case study of a human fungal pathogen outbreak. We anticipate that these discussions will help prioritize fungal research in Canada, and we welcome all researchers to join this nationwide effort to enhance knowledge dissemination and funding advocacy.

Objective: The development of these guidelines is sponsored by the American Association of Clinical Endocrinologists (AACE) Board of Directors and American College of Endocrinology (ACE) Board of Trustees and adheres with published AACE protocols for the standardized production of clinical practice guidelines (CPGs). Methods: Recommendations are based on diligent reviews of the clinical evidence with transparent incorporation of subjective factors, according to established AACE/ACE guidelines for guidelines protocols. Results: The Executive Summary of this 2020 updated guideline contains 52 recommendations: 21 Grade A (40%), 24 Grade B (46%), 7 Grade C (14%), and no Grade D (0%). These detailed, evidence-based recommendations allow for nuance-based clinical decision-making that addresses multiple aspects of real-world care of patients. The evidence base presented in the subsequent Appendix provides relevant supporting information for the Executive Summary recommendations. This update contains 368 citations: 123 (33.5%) evidence level (EL) 1 (highest), 132 (36%) EL 2 (intermediate), 20 (5.5%) EL 3 (weak), and 93 (25%) EL 4 (lowest). New or updated topics in this CPG include: clarification of the diagnosis of osteoporosis, stratification of the patient according to high-risk and very-high-risk features, a new dual-action therapy option, and transitions from therapeutic options. Conclusion: This guideline is a practical tool for endocrinologists, physicians in general, regulatory bodies, health-related organizations, and interested laypersons regarding the diagnosis, evaluation, and treatment of post-menopausal osteoporosis.

Etidronate is a non-nitrogen-containing bisphosphonate. Because it binds with calcium and inhibits crystal formation and dissolution, it was considered by Procter & Gamble as an additive to toothpaste (to prevent build-up of tartar) and detergent (to bind calcium and increase sudsing in "hard" water). The first clinical use (1968) was for fibrodysplasia ossificans progressiva. The first approved clinical use (1977) was for treatment of Paget's disease of bone. Other approved indications are hypercalcemia of malignancy and heterotopic ossification, with a host of off-label uses (including fibrous dysplasia, periodontal disease, multiple myeloma, neuropathic arthropathy, pulmonary microlithiasis, diabetic retinopathy, bone metastases, melorheostosis, urinary stone disease, periodontal disease, etc.). Unique among bisphosphonates, etidronate (oral therapy) results in hyperphosphatemia, increased tubular reabsorption of phosphorus and increased levels of 1,25-dihydroxyvitamin D. The dose that reduces bone resorption is close to the dose that impairs mineralization; prolonged high-dose use can result in osteomalacia and bone fractures. Intermittent cyclic etidronate for osteoporosis resulted in favorable changes in bone density and histomorphometry (no mineralization defect) as well as a decrease in vertebral fracture rates in postmenopausal women with osteoporosis. Later studies showed similar effects in men with osteoporosis and patients with glucocorticoid-induced osteoporosis. Although its use for osteoporosis has given way to newer bisphosphonates and other agents, because of its unique properties, it remains the bisphosphonate of choice for treatment of heterotopic ossification.

Summary The polyextremotolerant black yeast Exophiala dermatitidis is a tractable model system for investigation of adaptations that support growth under extreme conditions. Foremost among these adaptations are melanogenesis and carotenogenesis. A particularly important question is their metabolic production cost. However, investigation of this issue has been hindered by a relatively poor systems-level understanding of E. dermatitidis metabolism. To address this challenge, a genome-scale model (iEde2091) was developed. Using iEde2091, carotenoids were found to be more expensive to produce than melanins. Given their overlapping protective functions, this suggests that carotenoids have an underexplored yet important role in photo-protection. Furthermore, multiple defensive pigments with overlapping functions might allow E. dermatitidis to minimize cost. Because iEde2091 revealed that E. dermatitidis synthesizes the same melanins as humans and the active sites of the key tyrosinase enzyme are highly conserved this model may enable a broader understanding of melanin production across kingdoms., Graphical Abstract, Highlights • Exophiala dermatitidis can be a model polyextremotolerant and melaninized organism • Its genome-scale model is reconstructed to study melanin and carotenoid metabolism • The shadow price analysis indicates a potential underexplored role of carotenoids • Comparisons between human and E. dermatitidis melanin synthesis are made, Microbiology; Bioinformatics; Metabolic Engineering

Although treatment for osteoporosis is recommended by U.S. clinical guidelines, a lack of diagnosis and treatment is common among patients with osteoporotic fractures.To determine the rates of osteoporosis diagnosis and treatment before and after various types of fractures.This was a retrospective claims analysis using data from the Humana Medicare Advantage claims (Medicare group) and Optum Insight Clinformatics Data Mart commercial claims (Commercial group). Patients included in the study had a claim for a qualifying fracture occurring between January 2008 and December 2013 (the index fracture), were continuously enrolled in the health plan for ≥ 1 year before and after the index fracture, and were aged ≥ 65 years in the Medicare group or ≥ 50 years in the Commercial group at the time of the index fracture. Fragility fractures and osteoporosis diagnoses were identified from ICD-9-CM codes. Treatment for osteoporosis included oral and injectable therapies identified by National Drug Code numbers and Healthcare Common Procedure Coding System codes. Diagnosis and treatment rates were assessed during the 1-year periods before and after the index fracture. All analyses were conducted by fracture type (vertebral, hip, nonhip/nonvertebral [NHNV], and multiple), with stratification by age and sex. No comparisons were made between the Medicare and Commercial groups; rather, McNemar tests were used to compare prefracture versus postfracture diagnosis and treatment rates within each group.For inclusion in the Medicare group, 45,603 patients were identified, and 54,145 patients were identified for the Commercial group. In the prefracture period, the osteoporosis diagnosis rates ranged from 12.0% (NHNV) to 21.5% (vertebral) in the Medicare group and from 5.3% (NHNV) to 12.1% (vertebral) in the Commercial group. In the postfracture period, diagnosis rates significantly increased (P0.001)-and nearly doubled-for all fracture types but did not exceed 42.1% (vertebral) in the Medicare group and 27.7% (vertebral) in the Commercial group. Pre-index treatment rates were similarly low, ranging from 9.4% (hip) to 16.6% (vertebral) among Medicare patients, and 7.5% (NHNV) to 14.4% (vertebral) in Commercial patients. Osteoporosis treatment rates improved significantly in the postfracture year, ranging from 12.5% (NHNV) to 26.5% (vertebral) among Medicare patients, and 8.3% (NHNV) to 21.4% (vertebral) in Commercial patients. Larger increases in diagnosis rates and smaller increases in treatment rates were observed in stratified analyses of men and women and of different age groups, with women and older patients having higher overall rates of diagnosis and treatment before and after fracture.In men and women, osteoporosis diagnosis rates were low before the index fracture and improved substantially after the fracture, yet still remained low overall (under 50%). Osteoporosis treatment rates among patients experiencing a fracture were low before the index fracture and improved only minimally afterwards.This study was funded by MerckCo. Other than through the employer relationship disclosed here, MerckCo. did not have a role in the study design, data collection, interpretation of the data, in writing of the manuscript, or in the decision to submit the manuscript for publication. Weaver is an employee of MerckCo. Sajjan was an employee of MerckCo. and owned stock in the company at the time of the study. Lewiecki has received consulting and/or speaker honoraria from MerckCo., AbbVie, AgNovos Healthcare, Alexion Pharmaceuticals, Amgen, Eli Lilly and Company, Radius Health, Shire, and TheraNova, along with research grant support from MerckCo., Amgen, and Eli Lilly and Company, and serves as a board member for the National Osteoporosis Foundation, the International Society for Clinical Densitometry, and the Osteoporosis Foundation of New Mexico. Harris has received consulting honoraria from MerckCo., Alexion Pharmaceuticals, Amgen, Eli Lilly and Company, Gilead Sciences, Primus Pharmaceuticals, and Radius Health. Study concept and design were contributed by Weaver and Sajjan. Sajjan collected the data, and data interpretation was performed by all the authors. The manuscript was written and revised by Weaver, Lewiecki, and Harris.

The prevalence and cost of subsequent fractures among patients with an incident fracture are not well defined.To assess the prevalence of, and costs associated with, subsequent fractures in the year after an incident fracture.This was a retrospective claims database analysis using data from Humana Medicare Advantage claims (Medicare group) and Optum Insight Clinformatics Data Mart commercial claims (commercial group). Patients included in the study had a claim for a qualifying fracture occurring between January 2008 and December 2013 (index fracture), were continuously enrolled in the health plan for ≥ 1 year before and after the index fracture, and were aged ≥ 65 years in the Medicare group or ≥ 50 years in the commercial group at the time of the index fracture. Subsequent fractures were identified by ICD-9-CM codes and were defined as the second fracture occurring ≥ 3 to ≤ 12 months after the index fracture (≥ 6 to ≤ 12 months for fractures at the same site as the index fracture). Rates of subsequent fractures were calculated as the number of patients who had a subsequent fracture divided by the total sample size. After propensity matching of demographic and clinical variables, we determined the total medical and pharmacy costs accrued within 1 year of the index fracture by patients with and without a subsequent fracture. Health care costs were compared between patients with and without a subsequent fracture using McNemar's test.A total of 45,603 patients were included in the Medicare group, and 54,145 patients were included in the commercial group. In the Medicare group, 7,604 (16.7%) patients experienced a subsequent fracture. The proportion of patients with a subsequent fracture was highest among patients with multiple index fractures (26.2%, n = 905), followed by those with hip (25.5%, n = 1,280) and vertebral (20.2%, n = 1,908) index fractures. In the commercial group, 6,256 (11.6%) patients experienced a subsequent fracture. The proportion of patients with a subsequent fracture paralleled those observed in the Medicare group: 24.5% (n = 808) in patients with multiple index fractures, 22.0% (n = 525) in those with hip fracture, and 14.5% (n = 841) in those with vertebral fracture. For vertebral, hip, and nonhip nonvertebral fractures, subsequent fractures were most frequently of the same type as the index fracture. The mean total health care cost (sum of medical and pharmacy costs) in the year following the incident fracture for the Medicare group was $27,844 and differed significantly between patients with and without a subsequent fracture ($34,897 vs. $20,790; P0.001). The mean total health care cost in the year following the incident fracture for the commercial group was $29,316 and also differed significantly between patients with and without a subsequent fracture ($39,501 vs. $19,131; P0.001).Among patients with an incident fracture, those who experienced a subsequent fracture in the following year had significantly higher health care costs than those who did not. A subsequent fracture is most likely to be of the same type as the initial fracture.This study was funded by MerckCo. Other than through the employer relationships disclosed here, MerckCo did not have a role in the study design, data collection, interpretation of the data, in writing of the manuscript, or in the decision to submit the manuscript for publication. Weaver and Marvos are employees of MerckCo. Sajjan was an employee of MerckCo. and owned stock in the company at the time of the study. Lewiecki has received consulting and/or speaker honoraria from Merck, AbbVie, AgNovos Healthcare, Alexion Pharmaceuticals, Amgen, Eli Lilly and Company, Radius Health, Shire, and TheraNova. Lewiecki has received research grant support from Merck, Amgen, and Eli Lilly and Company and serves as a board member for the National Osteoporosis Foundation, the International Society for Clinical Densitometry, and the Osteoporosis Foundation of New Mexico. Harris has received consulting honoraria from Merck, Alexion Pharmaceuticals, Amgen, Eli Lilly and Company, Gilead Sciences, Primus Pharmaceuticals, and Radius Health. Study concept and design were contributed by Weave and Sajjan. Lewiecki collected the data, and data interpretation was performed by all the authors. The manuscript was written and revised by Weaver, Lewiecki, and Harris.

There is a well-established literature dedicated to why couples divorce, transitions associated with divorce, and the impact of divorce on families. However, little is known about the divorce decision-making process. We conducted in-depth interviews with individuals who have recently considered divorce (n = 30) and asked specifically about the roles of 2 concepts in their decision-making process: clarity and confidence. Three major themes emerged from the data: (a) Clarity about a decision to divorce or stay married is desired, it fluctuates, and takes time to find; (b) pivotal moments can bring clarity; and (c) confidence (in the final decision) is desired. Clinical implications and directions for future research are discussed.

International audience; The radiation of life on Earth was accompanied by the diversification of multicellular body plans in the eukary-otic kingdoms Animalia, Plantae, Fungi and Chromista. Branching forms are ubiquitous in nature and evolved repeatedly in the above lineages. The developmental and genetic basis of branch formation is well studied in the three-dimensional shoot and root systems of land plants, and in animal organs such as the lung, kidney, mammary gland, vasculature, etc. Notably, recent thought-provoking studies combining experimental analysis and computational modeling of branching patterns in whole animal organs have identified global patterning rules and proposed unifying principles of branching morphogenesis. Filamentous branching forms represent one of the simplest expressions of the multicellular body plan and constitute a key step in the evolution of morphological complexity. Similarities between simple and complex branching forms distantly related in evolution are compelling, raising the question whether shared mechanisms underlie their development. Here, we focus on filamentous branching organisms that represent major study models from three distinct eukaryotic kingdoms, including the moss Physcomitrella patens (Plantae), the brown alga Ectocarpus sp. (Chromista), and the ascomycetes Neurospora crassa and Aspergillus nidulans (Fungi), and bring to light developmental regulatory mechanisms and design principles common to these lineages. Throughout the review we explore how the regulatory mechanisms of branching morphogenesis identified in other models, and in particular animal organs, may inform our thinking on filamentous systems and thereby advance our understanding of the diverse strategies deployed across the eukaryotic tree of life to evolve similar forms. Introduction The evolution of multicellularity was a prerequisite to the diversification of complex morphologies in living organisms. The multi-cellular body plan (as defined in [1]) has three basic variants that can be described by the number of planes that orient cell division , which is typically mirrored in development by the dimen-sionality of tissue growth. A single cell that cleaves repeatedly in one plane gives rise to unbranched uniseriate filaments, cleav-age in two planes gives rise to branching uniseriate filaments or pseudo-parenchymatous tissues, and cleavage in three planes leads to parenchymatous tissues [2-5]. Unicellularity represents the morphological condition preceding the origin of multicellular forms across the tree of life. The unbranched filament is likely the simplest and most ancient variant of the multicellular body plan, and filamentous branching forms represent a key step in the evolution of complex three-dimensional multicellular morphologies [6]. It is noteworthy that despite the constraints imposed by cell division patterns, development may also occur in three dimensions in branching filaments through the establishment of new growth directions when branch points are specified. Multi-cellularity arose repeatedly in the different eukaryotic kingdoms, leading to multiple independent acquisitions of branched fila-mentous forms. These forms have been maintained as a dominant (e.g., brown, red and green algae, fungi) or transient state

We calculate the bulk-viscous dissipation time for adiabatic density oscillations in nuclear matter at densities of 1-7 times nuclear saturation density and at temperatures ranging from 1 MeV, where corrections to previous low-temperature calculations become important, up to 10 MeV, where the assumption of neutrino transparency is no longer valid. Under these conditions, which are expected to occur in neutron star mergers, damping of density oscillations arises from beta equilibration via weak interactions. We find that for 1 kHz oscillations the shortest dissipation times are in the 5 to 20 ms range, depending on the equation of state, which means that bulk viscous damping could affect the dynamics of a neutron star merger. For higher frequencies the dissipation time can be even shorter., 13 pages v2: Matches journal version

In filamentous fungi, an important kinase responsible for adaptation to changes in available nutrients is cyclic AMP (cAMP)-dependent protein kinase (protein kinase A [PKA]). This kinase has been well characterized at a molecular level, but its systemic action and direct/indirect targets are generally not well understood in filamentous fungi. In this work, we used a pkaA deletion strain (ΔpkaA) to identify Aspergillus nidulans proteins for which phosphorylation is dependent (either directly or indirectly) on PKA. A combination of phosphoproteomic and transcriptomic analyses revealed both direct and indirect targets of PKA and provided a global perspective on its function. One of these targets was the transcription factor CreA, the main repressor responsible for carbon catabolite repression (CCR). In the ΔpkaA strain, we identified a previously unreported phosphosite in CreA, S319, which (based on motif analysis) appears to be a direct target of Stk22 kinase (AN5728). Upon replacement of CreA S319 with an alanine (i.e., phosphonull mutant), the dynamics of CreA import to the nucleus are affected. Collectively, this work provides a global overview of PKA function while also providing novel insight regarding significance of a specific PKA-mediated phosphorylation event. IMPORTANCE The cyclic AMP (cAMP)-dependent protein kinase A (PKA) signaling pathway is well conserved across eukaryotes, and previous work has shown that it plays an important role in regulating development, growth, and virulence in a number of fungi. PKA is activated in response to extracellular nutrients and acts to regulate metabolism and growth. While a number of components in the PKA pathway have been defined in filamentous fungi, current understanding does not provide a global perspective on PKA function. Thus, this work is significant in that it comprehensively identifies proteins and functional pathways regulated by PKA in a model filamentous fungus. This information enhances our understanding of PKA action and may provide information on how to manipulate it for specific purposes.

Lichens are traditionally defined as a symbiotic relationship between fungi and algae and/or cyanobacteria. This union forms a unique structure called the thallus, which attaches to surfaces such as rocks and tree bark. Recent reports challenge the view that lichens are comprised of one fungus and one photobiont, and instead suggest that they are a consortium of microbes. Much of lichen biology remains unknown as most of our knowledge of lichens is limited to morphological characteristics with little to no functional analysis of lichen genes. However, lichens and biofilms share many similar physiological traits which when compared may assist in our understanding of lichens. Similarities between the two are rooted in their lifestyle, where these microbes and their extracellular products attach themselves to a surface and grow in a community structure. Biofilms and lichens alike have distinct features that allow for their lifestyle and identification, such as specific developmental patterns, formation of an extracellular matrix, and their ability to resist abiotic stressors. We argue here that one can gain insight into the cellular processes and evolutionary origins of lichens, which are currently undetermined, by applying knowledge gleaned from studies on microbial biofilms, with a particular focus on fungal biofilms.

Supernovae and cooling neutron stars have long been used to constrain the properties of axions, such as their mass and interactions with nucleons and other Standard Model particles. We investigate the prospects of using neutron star mergers as a similar location where axions can be probed in the future. We examine the impact axions would have on mergers, considering both the possibility that they free-stream through the dense nuclear matter and the case where they are trapped. We calculate the mean free path of axions in merger conditions, and find that they would free-stream through the merger in all thermodynamic conditions. In contrast to previous calculations, we integrate over the entire phase space while using a relativistic treatment of the nucleons, assuming the matrix element is momentum-independent. In particular, we use a relativistic mean field theory to describe the nucleons, taking into account the precipitous decrease in the effective mass of the nucleons as density increases above nuclear saturation density. We find that within current constraints on the axion-neutron coupling, axions could cool nuclear matter on timescales relevant to neutron star mergers. Our results may be regarded as first steps aimed at understanding how axions affect merger simulations and potentially interface with observations., v2: matches version accepted by JCAP

We show that the commonly used criterion for beta equilibrium in neutrino-transparent dense nuclear matter becomes invalid as temperatures rise above 1 MeV. Such temperatures are attained in neutron star mergers. By numerically computing the relevant weak interaction rates we find that the correct criterion for beta equilibrium requires an isospin chemical potential that can be as large as 10-20 MeV, depending on the temperature at which neutrinos become trapped., Comment: Section on neutrino mean free paths added. Discussion and plot of effect of isospin chemical potential on beta-equilibrium proton fraction added

In filamentous fungi, the formation of hyphal branches is a critical process that supports the ability of mycelia to radiate across and colonize growth substrates. Branching can occur at hyphal tips (apical branching) or from subapical hyphal compartments (lateral branching). The primary focus of this review is on lateral branching. Current understanding of the physiological and molecular mechanisms that underlie the formation of lateral branches is summarized. This includes emphasis on the spatial regulation of branch formation as well as the roles of the morphogenetic machinery in branch emergence. An improved understanding of hyphal branching will provide greater insight into the morphological differentiation of fungal mycelia.