Using dust shed from asteroids as microsamples to link remote measurements with meteorite classes.

Given the compositional diversity of asteroids, and their distribution in space, it is impossible to consider returning samples from each one to establish their origin. However, the velocity and molecular composition of primary minerals, hydrated silicates, and organic materials can be determined by in situ dust detector instruments. Such instruments could sample the cloud of micrometer-scale particles shed by asteroids to provide direct links to known meteorite groups without returning the samples to terrestrial laboratories. We extend models of the measured lunar dust cloud from LADEE to show that the abundance of detectable impact-generated microsamples around asteroids is a function of the parent body radius, heliocentric distance, flyby distance, and speed. We use Monte Carlo modeling to show that several tens to hundreds of particles, if randomly ejected and detected during a flyby, would be a sufficient number to classify the parent body as an ordinary chondrite, basaltic achondrite, or other class of meteorite. Encountering and measuring microsamples shed from near-Earth and Main Belt asteroids, coupled with complementary imaging and multispectral measurements, could accomplish a thorough characterization of small, airless bodies.

Effect of intraoperative hyperoxia on the incidence of surgical site infections: a meta-analysis.

BACKGROUND: Whether supplemental intraoperative oxygen reduces surgical site infections remains unclear. Recent recommendations from the World Health Organization and Center for Disease Control to routinely use high inspired oxygen concentrations to reduce infection risk have been widely criticized. We therefore performed a meta-analysis to evaluate the influence of inspired oxygen on infection risk, including a recent large trial. METHODS: A systematic literature search was performed. Primary analysis included all eligible trials. Sensitivity analyses distinguished studies of colorectal and non-colorectal surgeries, and excluded studies with high risk of bias. Another post-hoc sensitivity analysis excluded studies from one author that appear questionable. RESULTS: The primary analysis included 26 trials (N=14,710). The RR [95%CI] for wound infection was 0.81 [0.70, 0.94] in the high vs. low inspired oxygen groups. The effect remained significant in colorectal patients (N=10,469), 0.79 [0.66, 0.96], but not in other patients (N=4,241), 0.86 [0.69, 1.09]. When restricting the analysis to studies with low risk of bias, either by strict inclusion criteria (N=5,047) or by researchers' judgment (N=12,547), no significant benefit remained: 0.84 [0.67, 1.06] and 0.89 [0.76, 1.05], respectively. CONCLUSIONS: When considering all available data, intraoperative hyperoxia reduced wound infection incidence. However, no significant benefit remained when analysis was restricted to objective- or investigator-identified low-bias studies, although those analyses were not as well-powered. Meta-analysis of the most reliable studies does not suggest that supplemental oxygen substantively reduces wound infection risk, but more research is needed to fully answer this question.

Longitudinal and Transverse Instability of Ion Acoustic Waves.

Ion acoustic waves are found to be susceptible to at least two distinct decay processes. Which process dominates depends on the parameters. In the cases examined, the decay channel where daughter modes propagate parallel to the mother mode is found to dominate at larger amplitudes, while the decay channel where the daughter modes propagate at angles to the mother mode dominates at smaller amplitudes. Both decay processes may occur simultaneously and with onset thresholds below those suggested by fluid theory, resulting in the eventual multidimensional collapse of the mother mode to a turbulent state.

Effects of vestibular disorders on vestibular reflex and imagery.

The aim of this study was to establish the effect of vestibular lesion on vestibular imagery. Subjects were required to estimate verbally their passively travelled rotation angles in complete darkness, i.e., to activate vestibular imagery. During motion, the vestibulo-ocular reflex (VOR) was measured. Thus, we examined the coherence between the vestibulo-ocular reflex and self-rotation imagery, with vestibular-lesioned patients and healthy participants. Unilateral acute and chronic patients, bilateral patients, and healthy subjects were compared. The stimulus was a sequence of eight successive passive rotations, with four amplitudes (from 90° to 360°) in two directions. The VOR gain was lower in patients with unilateral lesions, for ipsilateral rotations. The healthy subjects had the highest gain and the bilateral group the lowest, on both rotation sides. Thanks to vestibular compensation after acute unilateral neuritis, the VOR gain increased in lesion side and decreased in healthy side, resulting in a similar gain in both sides. A deficit of vestibular imagery was found exclusively in patients with bilateral hyporeflexia, on both sides. The performance in vestibular imagery was good in the control group and correct in the unilateral patients. Finally, we found a significant correlation between the efficiency of the VOR and that of vestibular imagery, exclusively in the bilateral patients. The present study shows the complex relationship between vestibular imagery and the VOR. This imagery test contributes to another assessment of the spatial handicap of vestibular patients. It seems particularly interesting for patients with bilateral canal paresis and could be used to confirm this diagnosis.

Feline Epitheliotropic Mastocytic Conjunctivitis in 15 Cats.

Mast cell infiltration occurs in malignant, inflammatory (eg, allergic, infectious), and idiopathic disease processes in humans and animals. Here, we describe the clinical and histological features of a unique proliferative conjunctivitis occurring in 15 cats. Ocular specimens were examined histologically, and polymerase chain reaction (PCR) for feline herpesvirus 1 (FHV-1) was performed on ocular tissues obtained from 10 cats. Cats had a median age of 8 years (range: 7 months-17.5 years). The known median duration of ocular lesions prior to biopsy was 4 months (range: 1 week-3 years). Ocular disease was unilateral in 12 cats, and 9 cats had coexisting corneal disease. Clinically and histologically, proliferative or nodular conjunctival lesions were noted in 13 cats. The nictitating membrane was affected in 10 cats. Histologically, lesions were characterized by mixed inflammatory infiltrates with an abundance of Giemsa-positive and toluidine blue-positive intraepithelial and subepithelial mast cells, marked edema, and papillary epithelial hyperplasia. Feline herpesvirus 1 was demonstrated by PCR in 1 of 10 cats tested. Follow-up information was available for 14 cats: 8 had no recurrence during a median follow-up period of 17.5 months (range: 4.5-30 months), 2 underwent orbital exenteration, 3 had recurrence that was medically managed, and 1 cat had diffuse conjunctivitis at the time of biopsy and recurrence was deemed irrelevant. Various ocular medications were administered before and after surgical biopsy. This condition was designated as feline epitheliotropic mastocytic conjunctivitis, with intraepithelial mast cells being an essential feature and papillary epithelial proliferation being characteristic but not diagnostic alone. The condition appears to be uncommon and benign. Although the cause is unknown, an allergic component is possible.

Changes in the incidence and antimicrobial susceptibility of healthcare-associated infections in a New York hospital system, 2006-2012.

INTRODUCTION: National efforts to curtail healthcare-associated infections (HAI) proliferated recently, though data detailing progress over time are limited. This retrospective cohort study aims to describe changes in incidence and antimicrobial susceptibility of HAI in four New York City hospitals over seven years. METHODS: Electronic data were collected retrospectively for all patients discharged from 2006 through 2012. Previously validated computerized algorithms based on National Healthcare Safety Network criteria detected bloodstream infections, pneumonia, surgical site infections, and urinary tract infections with Enterococcus spp., Staphylococcus aureus, Streptococcus pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumoniae. Antimicrobial susceptibilities were obtained from electronic laboratory records. Logistic regression was used to assess changes in odds of acquiring an HAI and odds of antimicrobial resistance over time, controlling for age, gender, severity of illness, previous hospitalizations, and admission source. RESULTS: In total, 19,052 HAI were identified among 761,426 discharges. HAI rates fell for all organisms, all infection types, and within all hospitals. Odds of acquiring an HAI decreased significantly over time for all organisms. Resistance levels were stable for Enterococcus spp., S. aureus, A. baumannii, and S. pneumoniae. Multidrug resistance increased for P. aeruginosa and decreased for K. pneumoniae, though imipenem resistance among K. pneumoniae climbed sharply in 2011. CONCLUSIONS: This study suggests that HAI incidence rates are falling, possibly due to increased federal, state and local attention to healthcare quality and patient safety. Though we found no substantial reductions in resistance, recent national attention towards antimicrobial stewardship may precipitate a change in coming years.

Determining best practices in reconnoitering sites for habitability potential on Mars using a semi-autonomous rover: A GeoHeuristic Operational Strategies Test.

We tested science operations strategies developed for use in remote mobile spacecraft missions, to determine whether reconnoitering a site of potential habitability prior to in-depth study (a walkabout-first strategy) can be a more efficient use of time and resources than the linear approach commonly used by planetary rover missions. Two field teams studied a sedimentary sequence in Utah to assess habitability potential. At each site one team commanded a human "rover" to execute observations and conducted data analysis and made follow-on decisions based solely on those observations. Another team followed the same traverse using traditional terrestrial field methods, and the results of the two teams were compared. Test results indicate that for a mission with goals similar to our field case, the walkabout-first strategy may save time and other mission resources, while improving science return. The approach enabled more informed choices and higher team confidence in choosing where to spend time and other consumable resources. The walkabout strategy may prove most efficient when many close sites must be triaged to a smaller subset for detailed study or sampling. This situation would arise when mission goals include finding, identifying, characterizing or sampling a specific material, feature or type of environment within a certain area.

The response of the vestibulosympathetic reflex to linear acceleration in the rat.

The vestibulosympathetic reflex (VSR) increases blood pressure (BP) upon arising to maintain blood flow to the brain. The optimal directions of VSR activation and whether changes in heart rate (HR) are associated with changes in BP are still not clear. We used manually activated pulses and oscillatory linear accelerations of 0.2-2.5 g along the naso-occipital, interaural, and dorsoventral axes in isoflurane-anesthetized, male Long-Evans rats. BP and HR were recorded with an intra-aortic sensor and acceleration with a three-dimensional accelerometer. Linear regressions of BP changes in accelerations along the upward, downward, and forward axes had slopes of ≈3-6 mmHg · g-1 (P < 0.05). Lateral and backward accelerations did not produce consistent changes in BP. Thus upward, downward, and forward translations were the directions that significantly altered BP. HR was unaffected by these translations. The VSR sensitivity to oscillatory forward-backward translations was ≈6-10 mmHg · g-1 at frequencies of ≈0.1 Hz (0.2 g), decreasing to zero at frequencies above 2 Hz (1.8 g). Upward, 70° tilts of an alert rat increased BP by 9 mmHg · g-1 without changes in HR, indicating that anesthesia had not reduced the VSR sensitivity. The similarity in BP induced in alert and anesthetized rats indicates that the VSR is relatively insensitive to levels of alertness and that the VSR is likely to cause changes in BP through modification of peripheral vascular resistance. Thus the VSR, which is directed toward the cardiovascular system, is in contrast to the responses in the alert state that can produce sweating, alterations in BP and HR, and motion sickness.

The Role of Signaling via Aqueous Pore Formation in Resistance Responses to Amphotericin B.

Drug resistance studies have played an important role in the validation of antibiotic targets. In the case of the polyene antibiotic amphotericin B (AmB), such studies have demonstrated the essential role that depletion of ergosterol plays in the development of AmB-resistant (AmB-R) organisms. However, AmB-R strains also occur in fungi and parasitic protozoa that maintain a normal level of ergosterol at the plasma membrane. Here, I review evidence that shows not only that there is increased protection against the deleterious consequences of AmB-induced ion leakage across the membrane in these resistant pathogens but also that a set of events are activated that block the cell signaling responses that trigger the oxidative damage produced by the antibiotic. Such signaling events appear to be the consequence of a membrane-thinning effect that is exerted upon lipid-anchored Ras proteins by the aqueous pores formed by AmB. A similar membrane disturbance effect may also explain the activity of AmB on mammalian cells containing Toll-like receptors. These resistance mechanisms expand our current understanding of the role that the formation of AmB aqueous pores plays in triggering signal transduction responses in both pathogens and host immune cells.

Functional implications of a psychiatric risk variant within CACNA1C in induced human neurons.

Psychiatric disorders have clear heritable risk. Several large-scale genome-wide association studies have revealed a strong association between susceptibility for psychiatric disorders, including bipolar disease, schizophrenia and major depression, and a haplotype located in an intronic region of the L-type voltage-gated calcium channel (VGCC) subunit gene CACNA1C (peak associated SNP rs1006737), making it one of the most replicable and consistent associations in psychiatric genetics. In the current study, we used induced human neurons to reveal a functional phenotype associated with this psychiatric risk variant. We generated induced human neurons, or iN cells, from more than 20 individuals harboring homozygous risk genotypes, heterozygous or homozygous non-risk genotypes at the rs1006737 locus. Using these iNs, we performed electrophysiology and quantitative PCR experiments that demonstrated increased L-type VGCC current density as well as increased mRNA expression of CACNA1C in iNs homozygous for the risk genotype, compared with non-risk genotypes. These studies demonstrate that the risk genotype at rs1006737 is associated with significant functional alterations in human iNs, and may direct future efforts at developing novel therapeutics for the treatment of psychiatric disease.

Abnormal high-energy phosphate molecule metabolism during regional brain activation in patients with bipolar disorder.

Converging evidence suggests bioenergetic abnormalities in bipolar disorder (BD). In the brain, phosphocreatine (PCr) acts a reservoir of high-energy phosphate (HEP) bonds, and creatine kinases (CK) catalyze the transfer of HEP from adenosine triphosphate (ATP) to PCr and from PCr back to ATP, at times of increased need. This study examined the activity of this mechanism in BD by measuring the levels of HEP molecules during a stimulus paradigm that increased local energy demand. Twenty-three patients diagnosed with BD-I and 22 healthy controls (HC) were included. Levels of phosphorus metabolites were measured at baseline and during visual stimulation in the occipital lobe using (31)P magnetic resonance spectroscopy at 4T. Changes in metabolite levels showed different patterns between the groups. During stimulation, HC had significant reductions in PCr but not in ATP, as expected. In contrast, BD patients had significant reductions in ATP but not in PCr. In addition, PCr/ATP ratio was lower at baseline in patients, and there was a higher change in this measure during stimulation. This pattern suggests a disease-related failure to replenish ATP from PCr through CK enzyme catalysis during tissue activation. Further studies measuring the CK flux in BD are required to confirm and extend this finding.

Incidence and risk factors for community-associated methicillin-resistant Staphylococcus aureus in New York City, 2006-2012.

This study aims to describe changes in incidence and risk factors for community-associated methicillin resistant Staphylococcus aureus (CA-MRSA) infections upon admission to two New York City hospitals from 2006 to 2012. We examined the first hospitalization for adult patients using electronic health record and administrative data and determined the annual incidence/1000 admissions of total S. aureus, total MRSA, and CA-MRSA (within 48 h of admission) in clinical specimens over the study period. Logistic regression was used to identify factors associated with CA-MRSA in 2006 and 2012. In 137 350 admissions, the incidence of S. aureus, MRSA, and CA-MRSA/1000 admissions were 15·6, 7·0, and 3·5, respectively. The total S. aureus and MRSA isolations decreased significantly over the study period (27% and 25%, respectively) while CA-MRSA incidence was unchanged. CA-MRSA increased as a proportion of all MRSA between 2006 (46%) and 2012 (62%), and was most frequently isolated from respiratory (1·5/1000) and blood (0·7/1000) cultures. Logistic regression analysis of factors associated with isolation of CA-MRSA showed that age ⩾65 years [odds ratio (OR) 2·3, 95% confidence interval (CI) 1·2-4·5], male gender (OR 1·8, 95% CI 1·2-2·8) and history of renal failure (OR 2·6, 95% CI 1·6-4·2) were significant predictors of infection in 2006. No predictors were identified in 2012.

Squamous Papillomas of the Conjunctiva in Dogs: A Condition Not Associated With Papillomavirus Infection.

Papillomas of the conjunctival surface in people can be of viral or nonviral origin and are found in high association with human papillomavirus. Canine conjunctival papillomas are seldom described, and published accounts have mostly been associated with canine oral papillomavirus infection. Here, we describe conjunctival squamous papillomas that do not express papillomavirus proteins and compare them with papillomavirus-associated conjunctival papillomas. Conjunctival squamous papillomas presented a distinct histopathologic profile and lacked the cytopathic effects seen in viral papillomas. They appeared as exophytic, papilliferous, pedunculated lesions with delicate fronds and angular terminal margins. Squamous papillomas presented with a delicate fibrovascular core and were associated both clinically and grossly with a feeder vessel. Pigmentation was variable within the epithelium and stroma of these lesions, and inflammatory infiltrates were characteristically minimal. Conjunctival squamous papillomas resembled squamous papillomas of the skin; however, they lacked significant hyperkeratosis. Compared with conjunctival viral papillomas, these masses occurred in older dogs and were smaller and solitary. Furthermore, polymerase chain reaction and immunohistochemistry failed to demonstrate papillomavirus genetic material and antigens in conjunctival squamous papillomas. Both viral and nonviral conjunctival papillomas were considered benign.

Functional linkage between genes that regulate osmotic stress responses and multidrug resistance transporters: challenges and opportunities for antibiotic discovery.

All cells need to protect themselves against the osmotic challenges of their environment by maintaining low permeability to ions across their cell membranes. This is a basic principle of cellular function, which is reflected in the interactions among ion transport and drug efflux genes that have arisen during cellular evolution. Thus, upon exposure to pore-forming antibiotics such as amphotericin B (AmB) or daptomycin (Dap), sensitive cells overexpress common resistance genes to protect themselves from added osmotic challenges. These genes share pathway interactions with the various types of multidrug resistance (MDR) transporter genes, which both preserve the native lipid membrane composition and at the same time eliminate disruptive hydrophobic molecules that partition excessively within the lipid bilayer. An increased understanding of the relationships between the genes (and their products) that regulate osmotic stress responses and MDR transporters will help to identify novel strategies and targets to overcome the current stalemate in drug discovery.

Cognitive variability in psychotic disorders: a cross-diagnostic cluster analysis.

BACKGROUND: Cognitive dysfunction is a core feature of psychotic disorders; however, substantial variability exists both within and between subjects in terms of cognitive domains of dysfunction, and a clear 'profile' of cognitive strengths and weaknesses characteristic of any diagnosis or psychosis as a whole has not emerged. Cluster analysis provides an opportunity to group individuals using a data-driven approach rather than predetermined grouping criteria. While several studies have identified meaningful cognitive clusters in schizophrenia, no study to date has examined cognition in a cross-diagnostic sample of patients with psychotic disorders using a cluster approach. We aimed to examine cognitive variables in a sample of 167 patients with psychosis using cluster methods. METHOD: Subjects with schizophrenia (n = 41), schizo-affective disorder (n = 53) or bipolar disorder with psychosis (n = 73) were assessed using a battery of cognitive and clinical measures. Cognitive data were analysed using Ward's method, followed by a K-means cluster approach. Clusters were then compared on diagnosis and measures of clinical symptoms, demographic variables and community functioning. RESULTS: A four-cluster solution was selected, including a 'neuropsychologically normal' cluster, a globally and significantly impaired cluster, and two clusters of mixed cognitive profiles. Clusters differed on several clinical variables; diagnoses were distributed amongst all clusters, although not evenly. CONCLUSIONS: Identification of groups of patients who share similar neurocognitive profiles may help pinpoint relevant neural abnormalities underlying these traits. Such groupings may also hasten the development of individualized treatment approaches, including cognitive remediation tailored to patients' specific cognitive profiles.

S.E. Mitchell Vascular Anomalies Flow Chart (SEMVAFC): a visual pathway combining clinical and imaging findings for classification of soft-tissue vascular anomalies.

Classification of vascular anomalies (VAs) is challenging due to overlapping clinical symptoms, confusing terminology in the literature and unfamiliarity with this complex entity. It is important to recognize that VAs include two distinct entities, vascular tumours (VTs) and vascular malformations (VaMs). In this article, we describe SE Mitchell Vascular Anomalies Flow Chart (SEMVAFC), which arises from a multidisciplinary approach that incorporates clinical symptoms, physical examination and magnetic resonance imaging (MRI) findings to establish International Society for the Study of Vascular Anomalies (ISSVA)-based classification of the VAs. SEMVAFC provides a clear visual pathway for physicians to accurately diagnose Vas, which is important as treatment, management, and prognosis differ between VTs and VaMs.

A call for early, effective, and scalable parent education programs for high-conflict separated/divorcing parents: A synthesized perspective from prevention science and family law.

Conflict between parents is stressful and disruptive to children living in the midst of parental separation or divorce. Although some level of post-separation/divorce conflict is understandable in an emotionally-charged separation/divorce, it undermines the extent to which parents protect their children from short- and long-term problems. In this article, we weave together a synthesized perspective informed by our respective training and experience in prevention science and family law on the role of parent education programs for high-conflict separating/divorcing parents. To do so, we first describe the research on the effects of high interparental conflict on children's outcomes and then discuss current approaches and challenges to reducing these negative effects by offering parent education programs for high-conflict separating/divorcing parents. Then, we propose and describe a new model for early, effective, and scalable parent education programs with the ultimate goal of protecting children after separation/divorce.

Impact of disclosure of radiographic test results on quality of life among patients with hernias: a randomized controlled trial.

PURPOSE: Hernias noted on radiographic imaging are common. We aimed to determine if informing patients of the presence of a clinically apparent or occult hernia on imaging would change their abdominal wall quality of life (AW-QOL). METHODS: This study was registered on clinicaltrials.gov (NCT04355819) in April 2020. Patients with a ventral hernia on elective CT abdomen/pelvis were enrolled. Patients underwent standardized abdominal examination by surgeons, and completed the modified Activities Assessment Scale, a validated, hernia-specific AW-QOL survey. On this scale, 1 is poor AW-QOL, 100 is perfect, and the minimally clinically important difference is five for a minor change. Patients were randomized to complete the one-year follow-up survey before or after being informed of the presence of a hernia on their imaging results. Primary outcome was follow-up AW-QOL adjusted for baseline AW-QOL. RESULTS: Of 169 patients randomized, 126 (75%) completed follow up at one-year. Among patients with occult hernias, those who completed the follow-up survey after being informed of having a hernia had a lower follow-up AW-QOL (mean difference - 7.6, 95% CI = - 20.8 to 5.7, p = 0.261) compared to those who completed the survey before being informed. Conversely, for patients with clinical hernias, those who completed the survey after being informed had higher adjusted follow-up AW-QOL (mean difference 10.3, 95% CI = - 3.0 to 23.6, p = 0.126) than those that completed it after. CONCLUSION: Conveying findings of hernias found on CT imaging can influence patients' AW-QOL. Future research should focus on identifying and addressing patients' concerns after disclosure of CT results.

A phase I study of the combination of ro4929097 and cediranib in patients with advanced solid tumours (PJC-004/NCI 8503).

BACKGROUND: The Notch signalling pathway has been implicated in tumour initiation, progression, angiogenesis and development of resistance to vascular endothelial growth factor (VEGF) targeting, providing a rationale for the combination of RO4929097, a γ-secretase inhibitor, and cediranib, a VEGF receptor tyrosine kinase inhibitor. METHODS: Patients received escalating doses of RO4929097 (on a 3 days-on and 4 days-off schedule) in combination with cediranib (once daily). Cycle 1 was 42 days long with RO4929097 given alone for the first 3 weeks followed by the co-administration of both RO4929097 and cediranib starting from day 22. Cycle 2 and onwards were 21 days long. Soluble markers of angiogenesis were measured in plasma samples. Archival tumour specimens were assessed for expression of three different components of Notch signalling pathway and genotyping. RESULTS: In total, 20 patients were treated in three dose levels (DLs). The recommended phase II dose was defined as 20 mg for RO4929097 on 3 days-on and 4 days-off schedule and 30 mg daily for cediranib. The most frequent treatment-related adverse events (AEs) were diarrhoea, hypertension, fatigue and nausea. Eleven patients had a best response of stable disease and one patient achieved partial response. We did not detect any correlation between tested biomarkers of angiogenesis or the Notch pathway and treatment effect. There was no correlation between mutational status and time to treatment failure. CONCLUSION: RO4929097 in combination with cediranib is generally well tolerated at the DLs tested. Preliminary evidence of antitumour efficacy with prolonged disease stabilisation in some patients with progressive malignancies warrants further clinical investigation of this treatment strategy.