The etiology of depression is still poorly understood, but two major causative hypotheses have been put forth: the monoamine deficiency and the stress hypotheses of depression. We evaluate these ...hypotheses using animal models of endogenous depression and chronic stress. The endogenously depressed rat and its control strain were developed by bidirectional selective breeding from the Wistar-Kyoto (WKY) rat, an accepted model of major depressive disorder (MDD). The WKY More Immobile (WMI) substrain shows high immobility/despair-like behavior in the forced swim test (FST), while the control substrain, WKY Less Immobile (WLI), shows no depressive behavior in the FST. Chronic stress responses were investigated by using Brown Norway, Fischer 344, Lewis and WKY, genetically and behaviorally distinct strains of rats. Animals were either not stressed (NS) or exposed to chronic restraint stress (CRS). Genome-wide microarray analyses identified differentially expressed genes in hippocampi and amygdalae of the endogenous depression and the chronic stress models. No significant difference was observed in the expression of monoaminergic transmission-related genes in either model. Furthermore, very few genes showed overlapping changes in the WMI vs WLI and CRS vs NS comparisons, strongly suggesting divergence between endogenous depressive behavior- and chronic stress-related molecular mechanisms. Taken together, these results posit that although chronic stress may induce depressive behavior, its molecular underpinnings differ from those of endogenous depression in animals and possibly in humans, suggesting the need for different treatments. The identification of novel endogenous depression-related and chronic stress response genes suggests that unexplored molecular mechanisms could be targeted for the development of novel therapeutic agents.
This research expands efforts to understand differences in NIH funding associated with the self-identified race and ethnicity of applicants. We collected data from 2,397 NIH Biographical Sketches ...submitted between FY 2003 and 2006 as part of new NIH R01 Type 1 applications to obtain detailed information on the applicants' training and scholarly activities, including publications. Using these data, we examined the association between an NIH R01 applicant's race or ethnicity and the probability of receiving an R01 award. The applicant's publication history as reported in the NIH biographical sketch and the associated bibliometrics narrowed the black/white funding gap for new and experienced investigators in explanatory models. We found that black applicants reported fewer papers on their Biosketches, had fewer citations, and those that were reported appeared in journals with lower impact factors. Incorporating these measures in our models explained a substantial portion of the black/white funding gap. Although these predictors influence the funding gap, they do not fully address race/ethnicity differences in receiving a priority score.
Summary The spectrum of bacterial pathogens encountered in cystic fibrosis (CF) lung disease has expanded over the last decade. In addition to established pathogens, such as Pseudomonas aeruginosa , ...Burkholderia cepacia complex and Staphylococcus aureus , novel Gram-negative non-fermenter bacteria and non-tuberculous mycobacteria have gained in clinical significance. Air sampling performed in inpatient and outpatient clinics, and analysis of cough aerosols expelled by CF patients provides evidence for potential airborne transmission of CF pathogens. Two outbreaks of ‘ Mycobacterium abscessus subsp. massiliense ’ have been reported among CF patients, raising the question of airborne transmission of non-tuberculous mycobacteria. In response to newer epidemiological evidence, international infection control guidance documents have changed. Guideline documents agree on the importance of specifications for ventilation when planning new CF inpatient facilities. New CF units should consider providing negative-pressure inpatient and outpatient rooms to diminish the risk of airborne contamination of ward corridors and communal areas. Air exchange rates of inpatient rooms and pulmonary function testing rooms need to be considered and optimized whenever possible. International guidelines disagree as to whether patients should be requested to wear masks in the hospital environment.
We present a search for anisotropic cosmic birefringence in 500 deg2 of southern sky observed at 150 GHz with the SPTpol camera on the South Pole Telescope. We reconstruct a map of cosmic ...polarization rotation anisotropies using higher-order correlations between the observed cosmic microwave background (CMB) E and B fields. We then measure the angular power spectrum of this map, which is found to be consistent with zero. The nondetection is translated into an upper limit on the amplitude of the scale-invariant cosmic rotation power spectrum, L(L + 1) CααL/2π < 0.10 × 10−4 rad2 (0.033 deg2, 95% C.L.). This upper limit can be used to place constraints on the strength of primordial magnetic fields, B1 Mpc < 17 nG (95% C.L.), and on the coupling constant of the Chern-Simons electromagnetic term gaγ < 4.0 × 10−2/HI (95% C.L.), where HI is the inflationary Hubble scale. For the first time, we also cross-correlate the CMB temperature fluctuations with the reconstructed rotation angle map, a signal expected to be nonvanishing in certain theoretical scenarios, and find no detectable signal. We perform a suite of systematics and consistency checks and find no evidence for contamination.
Macromolecular crowding has a profound impact on reaction rates and the physical properties of the cell interior, but the mechanisms that regulate crowding are poorly understood. We developed ...genetically encoded multimeric nanoparticles (GEMs) to dissect these mechanisms. GEMs are homomultimeric scaffolds fused to a fluorescent protein that self-assemble into bright, stable particles of defined size and shape. By combining tracking of GEMs with genetic and pharmacological approaches, we discovered that the mTORC1 pathway can modulate the effective diffusion coefficient of particles ≥20 nm in diameter more than 2-fold by tuning ribosome concentration, without any discernable effect on the motion of molecules ≤5 nm. This change in ribosome concentration affected phase separation both in vitro and in vivo. Together, these results establish a role for mTORC1 in controlling both the mesoscale biophysical properties of the cytoplasm and biomolecular condensation.
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•GEMs enable high-throughput microrheology in unperturbed living cells•mTORC1 controls diffusion by tuning ribosome concentration•Diffusion can be accurately predicted as a function of ribosome concentration•Crowding of the cytoplasm by ribosomes increases phase separation
mTORC1 signaling controls phase transitions in the cytoplasm through its effects on molecular crowding.
Objectives
To aid the development of treatment for cognitive impairment in bipolar disorder, the International Society for Bipolar Disorders (ISBD) convened a task force to create a consensus‐based ...guidance paper for the methodology and design of cognition trials in bipolar disorder.
Methods
The task force was launched in September 2016, consisting of 18 international experts from nine countries. A series of methodological issues were identified based on literature review and expert opinion. The issues were discussed and expanded upon in an initial face‐to‐face meeting, telephone conference call and email exchanges. Based upon these exchanges, recommendations were achieved.
Results
Key methodological challenges are: lack of consensus on how to screen for entry into cognitive treatment trials, define cognitive impairment, track efficacy, assess functional implications, and manage mood symptoms and concomitant medication. Task force recommendations are to: (i) enrich trials with objectively measured cognitively impaired patients; (ii) generally select a broad cognitive composite score as the primary outcome and a functional measure as a key secondary outcome; and (iii) include remitted or partly remitted patients. It is strongly encouraged that trials exclude patients with current substance or alcohol use disorders, neurological disease or unstable medical illness, and keep non‐study medications stable. Additional methodological considerations include neuroimaging assessments, targeting of treatments to illness stage and using a multimodal approach.
Conclusions
This ISBD task force guidance paper provides the first consensus‐based recommendations for cognition trials in bipolar disorder. Adherence to these recommendations will likely improve the sensitivity in detecting treatment efficacy in future trials and increase comparability between studies.
We present a measurement of the cosmic microwave background (CMB) temperature power spectrum using data from the recently completed South Pole Telescope Sunyaev-Zel'dovich (SPT-SZ) survey. We report ...CMB temperature anisotropy power over the multipole range 650 < l < 3000. We fit the SPT bandpowers, combined with the 7 yr Wilkinson Microwave Anisotropy Probe (WMAP7) data, with a six-parameter ACDM cosmological model and find that the two datasets are consistent and well fit by the model. Adding SPT measurements significantly improves ACDM parameter constraints; in particular, the constraint on theta sub(s) tightens by a factor of 2.7. The impact of gravitational lensing is detected at 8.1sigma, the most significant detection to date. These new constraints on n sub(s) and r have significant implications for our understanding of inflation, which we discuss in the context of selected single-field inflation models.
Objectives
Cognition is a new treatment target to aid functional recovery and enhance quality of life for patients with bipolar disorder. The International Society for Bipolar Disorders (ISBD) ...Targeting Cognition Task Force aimed to develop consensus‐based clinical recommendations on whether, when and how to assess and address cognitive impairment.
Methods
The task force, consisting of 19 international experts from nine countries, discussed the challenges and recommendations in a face‐to‐face meeting, telephone conference call and email exchanges. Consensus‐based recommendations were achieved through these exchanges with no need for formal consensus methods.
Results
The identified questions were: (I) Should cognitive screening assessments be routinely conducted in clinical settings? (II) What are the most feasible screening tools? (III) What are the implications if cognitive impairment is detected? (IV) What are the treatment perspectives? Key recommendations are that clinicians: (I) formally screen cognition in partially or fully remitted patients whenever possible, (II) use brief, easy‐to‐administer tools such as the Screen for Cognitive Impairment in Psychiatry and Cognitive Complaints in Bipolar Disorder Rating Assessment, and (III) evaluate the impact of medication and comorbidity, refer patients for comprehensive neuropsychological evaluation when clinically indicated, and encourage patients to build cognitive reserve. Regarding question (IV), there is limited evidence for current evidence‐based treatments but intense research efforts are underway to identify new pharmacological and/or psychological cognition treatments.
Conclusions
This task force paper provides the first consensus‐based recommendations for clinicians on whether, when, and how to assess and address cognition, which may aid patients’ functional recovery and improve their quality of life.
A perfluorocarbon (PFC) investigated for treatment of traumatic brain injury (TBI) delivers oxygen to support brain function, but causes transient thrombocytopenia. TBI can cause acute inflammation ...with resulting thrombocytopenia; an interaction between the PFC effects and TBI inflammation might exacerbate thrombocytopenia. Therefore, PFC effects on platelet (PLT) function and hemostasis in a lipopolysaccharide (LPS) model of inflammation in the baboon were studied. Animals were randomized to receive saline ±LPS, and ± one of two doses of PFC. PLT count, transmission electron microscopy, and microparticle populations were quantified at baseline (BL) and at 2, 24, 48, 72, and 96 hours; hemostatic parameters for aggregometry and for blood clotting were measured at baseline (BL) and days 3 and 4. Injection of vehicle and LPS caused thrombocytopenia within hours; PFCs caused delayed thrombocytopenia beginning 48 hours post-infusion. LPS+PFC produced a more prolonged PLT decline and decreased clot strength. LPS+PFC increased ADP-stimulated aggregation, but PFC alone did not. Microparticle abundance was greatest in the LPS+PFC groups. LPS+PFC caused diffuse microvascular hemorrhage and death in 2 of 5 baboons in the low dose LPS-PFC group and 2 of 2 in the high dose LPS-PFC group. Necropsy and histology suggested death was caused by shock associated with hemorrhage in multiple organs. Abnormal morphology of platelets and red blood cells were notable for PFC inclusions. In summary, PFC infusion caused clinically significant thrombocytopenia and exacerbated LPS-induced platelet activation. The interaction between these effects resulted in decreased hemostatic capacity, diffuse bleeding, shock and death.
We present a detection-significance-limited catalog of 21 Sunyaev-Zel'dovich-selected galaxy clusters. These clusters, along with one unconfirmed candidate, were identified in 178 deg2 of sky ...surveyed in 2008 by the South Pole Telescope (SPT) to a depth of 18 Delta *mK arcmin at 150 GHz. Optical imaging from the Blanco Cosmology Survey (BCS) and Magellan telescopes provided photometric (and in some cases spectroscopic) redshift estimates, with catalog redshifts ranging from z = 0.15 to z>1, with a median z = 0.74. Of the 21 confirmed galaxy clusters, 3 were previously identified as Abell clusters, 3 were presented as SPT discoveries in Staniszewski et al., and 3 were first identified in a recent analysis of BCS data by Menanteau et al.; the remaining 12 clusters are presented for the first time in this work. Simulated observations of the SPT fields predict the sample to be nearly 100% complete above a mass threshold of M 200 5 X 1014 M h --1 at z = 0.6. This completeness threshold pushes to lower mass with increasing redshift, dropping to ~4 X 1014 M h --1 at z = 1. The size and redshift distribution of this catalog are in good agreement with expectations based on our current understanding of galaxy clusters and cosmology. In combination with other cosmological probes, we use this cluster catalog to improve estimates of cosmological parameters. Assuming a standard spatially flat wCDM cosmological model, the addition of our catalog to the WMAP seven-year results yields Delta *s8 = 0.81 ? 0.09 and w = --1.07 ? 0.29, a ~50% improvement in precision on both parameters over WMAP7 alone.
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