A transcriptomic atlas of mouse cerebellar cortex comprehensively defines cell types.

The cerebellar cortex is a well-studied brain structure with diverse roles in motor learning, coordination, cognition and autonomic regulation. However,  a complete inventory of cerebellar cell types is currently lacking. Here, using recent advances in high-throughput transcriptional profiling1-3, we molecularly define cell types across individual lobules of the adult mouse cerebellum. Purkinje neurons showed considerable regional specialization, with the greatest diversity occurring in the posterior lobules. For several types of cerebellar interneuron, the molecular variation within each type was more continuous, rather than discrete. In particular, for the unipolar brush cells-an interneuron population previously subdivided into discrete populations-the continuous variation in gene expression was associated with a graded continuum of electrophysiological properties. Notably, we found that molecular layer interneurons were composed of two molecularly and functionally distinct types. Both types show a continuum of morphological variation through the thickness of the molecular layer, but electrophysiological recordings revealed marked differences between the two types in spontaneous firing, excitability and electrical coupling. Together, these findings provide a comprehensive cellular atlas of the cerebellar cortex, and outline a methodological and conceptual framework for the integration of molecular, morphological and physiological ontologies for defining brain cell types.

The adaptive response to alternative carbon sources in the pathogen Candida albicans involves a remodeling of thiol- and glutathione-dependent redox status.

Candida albicans is an opportunist pathogen responsible for a large spectrum of infections, from superficial mycosis to systemic diseases known as candidiasis. During infection in vivo, Candida albicans must adapt to host microenvironments and this adaptive response is crucial for the survival of this organism, as it facilitates the effective assimilation of alternative carbon sources others than glucose. We performed a global proteomic analysis on the global changes in protein abundance in response to changes in micronutrient levels, and, in parallel, explored changes in the intracellular redox and metabolic status of the cells. We show here that each of the carbon sources considered - glucose, acetate and lactate - induces a unique pattern of response in C. albicans cells, and that some conditions trigger an original and specific adaptive response involving the adaptation of metabolic pathways, but also a complete remodeling of thiol-dependent antioxidant defenses. Protein S-thiolation and the overproduction of reduced glutathione are two components of the response to high glucose concentration. In the presence of acetate, glutathione-dependent oxidative stress occurs, reduced thiol groups bind to proteins, and glutathione is exported out of the cells, these changes probably being triggered by an increase in glutathione-S-transferases. Overall, our results suggest that the role of cellular redox status regulation and defenses against oxidative stress, including the thiol- and glutathione-dependent response, in the adaptive response of C. albicans to alternative carbon sources should be reconsidered.

Exploring parents' experiences and holistic needs following late miscarriage: a narrative systematic review.

BACKGROUND: Up to 2% of all pregnancies result in pregnancy loss between 14 + 0 and 23 + 6 weeks' gestation, which is defined as 'late miscarriage'. Lack of consensus about definition of viability paired with existing multiple definitions of perinatal loss make it difficult to define the term 'late miscarriage'. Parents who experience late miscarriage often have had reassuring scan-milestones, which established their confidence in healthy pregnancy progression and identity formation, which socially integrates their baby into their family. The clinical lexicon alongside the lack of support offered to parents experiencing late miscarriage may disclaim their needs, which has potential to cause adverse psychological responses. AIM: To review what primary research reports about parents' experiences and their perceived holistic needs following late miscarriage. METHODS: A narrative systematic review was carried out. Papers were screened based on gestational age at time of loss (i.e. between 14 + 0 and 23 + 6 weeks' gestation). The focus was set on experience and holistic needs arising from the loss rather than its clinical care and pathophysiology. Studies were selected using PRISMA-S checklist, and quality assessed using the Critical Appraisal Skills Program (CASP) tool. Thematic analysis was used to guide the narrative synthesis of findings. RESULTS: Six studies met the inclusion criteria. Three main themes emerged: communication and information-giving; feelings post-event; and impact of support provision. CONCLUSION: Literature about the experience of late miscarriage is scarce, with what was found reporting a lack of compassionate and individually tailored psychological follow-up care for parents following late miscarriage. Hence, more research in this arena is required to inform and develop this area of maternity care provision.

Translation and validation of the Czech Republic version of the Birth Satisfaction Scale-Revised (BSS-R).

BACKGROUND: Satisfaction with the birth experience has been established to be critical for the wellbeing of the mother. The Birth Satisfaction Scale-Revised (BSS-R) is a brief and psychometrically robust multi-dimensional self-report tool designed to assess birth experience. The current investigation sought to translate and validate a Czech Republic version of the BSS-R (CZ-BSS-R). METHODS: Following translation psychometric assessment of the CZ-BSS-R was undertaken using a cross-sectional design. A between-subjects design was incorporated in order to evaluate known-groups validity evaluation of the translated measure. Four hundred and sixty-five Czech-speaking women within the Czech Republic took part in the study. Confirmatory factor analysis was undertaken and divergent and convergent validity and internal consistency characteristics also evaluated. RESULTS: The CZ-BSS-R was observed to have excellent psychometric properties and conceptually and measurement faithful to the original English-language measure. Consistent with previous investigations using the BSS-R significant differences were found in scores as a function of delivery type. CONCLUSIONS: The CZ-BSS-R is a valid, robust and reliable measure of birth experience and suitable for use with Czech-speaking women in the Czech Republic. The study highlighted that instrument and emergency Caesarean section were associated with a lower level of birth satisfaction compared to vaginal delivery.

Translation and validation of Vietnamese version of the Birth Satisfaction Scale-Revised (BSS-R).

BACKGROUND: The 10-item Birth Satisfaction Scale-Revised (BSS-R) is a quick and easy survey instrument recommended by the International Consortium for Health Outcome Measures as the tool of choice for measuring women's birth satisfaction. AIM: To translate and validate a Vietnamese-language version of the BSS-R. METHOD: A quantitative cross-sectional method was used to gather data post translation and back-translation of a Vietnamese version of the BSS-R (VN-BSS-R). Data collected were psychometrically evaluated using key indices of validity and reliability. PARTICIPANTS: Vietnamese women who were within one month postpartum of birth (N = 383) took part in the study. RESULTS: Findings illustrate that a two-factor model offered excellent psychometric properties. With the two-factor VN-BSS-R, five items loaded onto a subscale 'Positive birth experiences' and the other five onto a second subscale 'Negative birth experiences'. This two-factor model offered a fit to data (root mean square error of approximation [RMSEA] = 0.07, 90% confidence interval [CI] [0.05, 0.09], root square mean residual [RMSE] = 0.04 and comparative fit index [CFI] = 0.97). Mean scores for the exploratory factor analysis [EFA]-derived 'positive' and 'negative' sub-scales were 17.12 (SD 2.34) and 8.40 (SD 4.18) respectively. CONCLUSION: The translated and validated VN-BSS-R is a psychometrically robust tool for measuring birth satisfaction in Vietnamese postpartum women.The VN-BSS-R is available for use to measure experiences and perceptions of intrapartum care received by Vietnamese women.

Efficacy of chemotherapy according to BRCA status in patients with high-grade serous ovarian carcinoma at first platinum-sensitive relapse.

OBJECTIVE: Chemotherapy for high-grade serous ovarian cancers in platinum-sensitive relapse includes carboplatin/paclitaxel, carboplatin/gemcitabine, and carboplatin/pegylated liposomal doxorubicin. According to in vitro data, BRCA mutated patients are sensitive to replicative stress agents but BRCA status is not yet used for the choice of chemotherapy at relapse. Our aim was to assess these doublets according to BRCA status in first platinum-sensitive relapse. METHODS: The ESME ovarian cancer database comprises a multicenter retrospective cohort of patients with ovarian cancer treated in French cancer centers between January 2011 and December 2017. Patients with high-grade serous ovarian cancers at first platinum-sensitive relapse who received one of these doublets were included. The objective was to compare progression-free survival of each chemotherapy doublet according to BRCA status. RESULTS: Among the 10 263 patients in the database, 1539 patients had a first platinum-sensitive relapse: 825 BRCA wild type patients (53.6%) and 304 BRCA mutated patients (19.8%) (7 patients had a homologous recombination mutation and BRCA status was unkown for 403 patients). Median progression-free survival was longer in BRCA mutated patients than in BRCA wild type patients when receiving carboplatin/pegylated liposomal doxorubicin without maintenance treatment (15.8 vs 11.8 months; p<0.001). In contrast, we observed no difference in patients treated with carboplatin/paclitaxel (14.6 vs 14.3 months, respectively; p=0.70) or in those treated with carboplatin/gemcitabine (12.0 vs 9.8 months, respectively; p=0.18). In BRCA wild type patients without maintenance, better progression-free survival occurred with carboplatin/paclitaxel (median progression-free survival 14.3 months) than with carboplatin/gemcitabine and carboplatin/pegylated liposomal doxorubicin (9.8 and 11.8 months, respectively; p=0.017). In BRCA mutated patients without maintenance, there was no difference between the three doublets (median progression-free survival of 14.6, 12.0, and 15.8 months with carboplatin/paclitaxel, carboplatin/gemcitabine, and carboplatin/pegylated liposomal doxorubicin, respectively; p=0.40). CONCLUSION: While treatment with carboplatin/paclitaxel, carboplatin/gemcitabine, and carboplatin/pegylated liposomal doxorubicin shows comparable efficacy in BRCA mutated patients, treatment with carboplatin/paclitaxel appears to be more effective than carboplatin/gemcitabine and carboplatin/pegylated liposomal doxorubicin in BRCA wild type patients with high-grade serous ovarian cancers at first platinum-sensitive relapse.

Precise characterization of nanometer-scale systems using interferometric scattering microscopy and Bayesian analysis.

Interferometric scattering microscopy can image the dynamics of nanometer-scale systems. The typical approach to analyzing interferometric images involves intensive processing, which discards data and limits the precision of measurements. We demonstrate an alternative approach: modeling the interferometric point spread function and fitting this model to data within a Bayesian framework. This approach yields best-fit parameters, including the particle's three-dimensional position and polarizability, as well as uncertainties and correlations between these parameters. Building on recent work, we develop a model that is parameterized for rapid fitting. The model is designed to work with Hamiltonian Monte Carlo techniques that leverage automatic differentiation. We validate this approach by fitting the model to interferometric images of colloidal nanoparticles. We apply the method to track a diffusing particle in three dimensions, to directly infer the diffusion coefficient of a nanoparticle without calculating a mean-square displacement, and to quantify the ejection of DNA from an individual lambda phage virus, demonstrating that the approach can be used to infer both static and dynamic properties of nanoscale systems.

Translation and validation of the Hindi-Indian version of the Birth Satisfaction Scale-Revised.

AIM: Critical to maternal outcome and development of a healthy and relationship between mother and baby, is the woman's perception of her birth experience. The Birth Satisfaction Scale-Revised (BSS-R) has been demonstrated to be psychometrically robust, easily administered, and scored self-report measure of birth experience. Aim of the study was to translate the UK-BSS-R into Hindi, collect data, and psychometrically validate an Indian (Hindi)-BSS-R. METHODS: Psychometric assessment of the Indian (Hindi)-BSS-R was undertaken following translation using a cross-sectional design. Evaluation of known-groups validity was undertaken using an embedded between-subjects component. Data were collected from (n = 312) postnatal Hindi speaking women in India. Measurement characteristics were assessed using confirmatory factor analysis, divergent validity and internal consistency analysis. RESULTS: The measurement properties of the Indian (Hindi)-BSS-R were observed to be equivocal, with the established tri-dimensional measurement model not achieving best fit to data. Instead, an alternative two-factor model offered an excellent fit to data. Significant differences were observed between Indian (Hindi)-BSS-R scores and family type and gestation term status, which highlights the relevance of these contextual aspects to the Indian birth experience. Internal consistency was observed to be low on some sub-scales, indicating the potential need for future revision. CONCLUSIONS: The Indian (Hindi)-BSS-R is a measure of birth experience, which accepting some measurement caveats, is acceptable for use with Hindi speaking women in India. Further research is required to determine if modification of some of the items is required to improve internal consistency.

Language Problems and ADHD Behaviors: Unique and Interactive Associations with School Readiness in a Socioeconomically Disadvantaged Preschool Sample.

This study examined the unique and interactive effects of receptive language ability and ADHD behaviors on six school readiness outcomes, over and above the effects of socioeconomic status, in 49 preschoolers (Mage = 3.98, SDage = .58; 53.06% female) recruited from Head Start-affiliated classrooms. Hierarchical regression analyses revealed unique positive associations between receptive language ability and cognitive and mathematics readiness, and unique negative associations between ADHD behaviors and social-emotional, physical, cognitive, and literacy readiness. Moderation analyses indicated that at higher, but not lower, levels of ADHD behaviors, lower receptive language ability was associated with lower social-emotional readiness. Results highlight that, when considered together, children's receptive language ability and ADHD behaviors vary in how they predict school readiness. Further, results provide preliminary evidence for ADHD behaviors as a risk factor in the association between receptive language deficits and social-emotional school readiness. Educational and clinical practice implications are discussed.

A scoping review of therapies used to treat psychological trauma post perinatal bereavement.

BACKGROUND: Up to 39% of women who experience perinatal bereavement proceed to develop Post-Traumatic-Stress-Disorder (PTSD), with this large proportion meriting treatment. Before setting-up a treatment service for postnatal women who are experiencing psychological trauma, it is important to identify what therapies have been used in-the-past to address this problem. AIM: To scope for research that has implemented therapies to treat psychological trauma post perinatal bereavement, for potential inclusion in a flexible treatment package. METHOD: A scoping review mapped coverage, range, and type of research that has reported on prior therapies used to treat psychological trauma post perinatal bereavement. FINDINGS: Due to the dearth of papers that directly addressed perinatal bereavement, we widened the scope of the review to view what treatments had been used to treat psychological trauma post-childbirth. Out of 23 studies that report on effectiveness of therapies used to treat psychological trauma post-childbirth, only 4-focused upon treating PTSD post perinatal bereavement (3 effective/1 ineffective). Successful treatments were reported by Kersting et al. (2013), who found CBT effective at reducing PTSD symptoms post-miscarriage, termination for medical reasons, and stillbirth (n = 33 & n = 115), and Navidian et al. (2s017)) found that 4-sessions of grief-counselling reduced trauma symptoms post-stillbirth in (n = 50) women. One study by Huberty et al. (2020found on-line yoga to be ineffective at reducing PTSD symptoms post-stillbirth. CONCLUSIONS: A dearth of research has explored effectiveness of therapies for treating psychological trauma post perinatal bereavement and post-childbirth, with need to develop and test a research informed flexible counselling package.

Factor structure and psychometric properties of the Birth Satisfaction Scale-Revised in Portuguese postpartum women.

OBJECTIVE: This study aims to develop a Portuguese-language version of the Birth Satisfaction Scale-Revised (BSS-R) for clinical and research use in Portugal (PT-BSS-R). The factor structure, its invariance across depression levels, and the internal consistency of the PT-BSS-R were analysed. METHOD: A sample of 1373 Portuguese-speaking postpartum women completed a sociodemographic and clinical form, the PT-BSS-R, and the Edinburgh Postnatal Depression Scale through an online survey tool. Four competing models were tested through confirmatory factor analyses and bifactor model-based psychometric indices were calculated. The internal consistency and the divergent/convergent validity are analysed. RESULTS: The psychometric properties of PT-BSS-R were found to be generally excellent. Both the original correlated three-factor model and the bifactor model exhibited a good fit to the data. Results from the bifactor model support the use of both the BSS-R total score and the subscale scores. Exemplary invariance findings were observed between groups stratified on the basis of depression screening. PT-BSS-R has demonstrated both divergent and convergent validity as well as internal consistency. CONCLUSION: PT-BSS-R is a psychometrically robust measure of birth satisfaction appropriate for clinical and research use in Portugal.

Translation and validation of the Dutch version of the Birth Satisfaction Scale-Revised (BSS-R).

BACKGROUND: Recent observations suggest birth satisfaction may be significantly associated with postpartum post-traumatic stress disorder (PP-PTSD). The Birth Satisfaction Scale-Revised (BSS-R) is increasingly used Internationally as a short, valid and reliable multi-dimensional measure of birth experience. The current study sought to develop a Dutch version of the BSS-R (D-BSS-R) for clinical and research application in the Netherlands. METHODS: Post-translation, a cross-sectional design with an embedded between-subjects component was used to evaluate key indices of validity and reliability of the D-BSS-R in a purposive sampled cohort of 244 Dutch-speaking women in the Netherlands. Confirmatory factor analysis, divergent, convergent and known-groups discriminant validity were evaluated as was the internal consistency of the measure. RESULTS: The D-BSS-R was found to be a generally valid and reliable measure of birth experience with the key measurement characteristics of the original English-language measure transferring well to the Dutch context. Statistically significant negative correlations were observed between all D-BSS-R sub-scales and a validated measure of PTSD. CONCLUSIONS: The D-BSS-R represents a valid and reliable measure of birth experience suitable and appropriate for use in the Netherlands. The study corroborates previous suggestions of linkage between birth satisfaction and PP-PTSD using a robust and diagnostically valid measure of trauma.

Loss of the world's smallest forests.

A large number of small forests typically harbor higher biodiversity than a small number of large forests totaling the same area, suggesting that small patches are disproportionately valuable for biodiversity conservation. However, policies often favor protection of large forest patches. Here we demonstrate a global trend of higher deforestation in small than large forest patches: the likelihood that a randomly selected forest plot disappeared between 1992 and 2020 increased with decreasing size of the forest patch containing that plot. Our results imply a disproportionate impact of forest loss on biodiversity relative to the total forest area removed. Achieving recent commitments of the post-2020 Global Biodiversity Framework will require revision of current policies and increased societal awareness of the importance of small habitat patches for biodiversity protection.

Blood donation motivators and barriers reported by young, first-time whole blood donors: Examining the association of reported motivators and barriers with subsequent donation behavior and potential sex, race, and ethnic group differences.

BACKGROUND: A greater understanding of young, first-time donor motivators and barriers is needed to address the ongoing challenge of retaining these essential donors. STUDY DESIGN AND METHODS: Structured interviews conducted with 508 young, first-time whole blood donors [66.1% female; Mean Age = 19.4 (SD = 2.5) years] were coded to identify reported motivators and barriers. Reported motivators and barriers were then examined for their association with attempted donation behavior over a 14-month follow-up, and for potential sex, race, and ethnic group differences in the frequency of endorsement. RESULTS: Prosocial motivation (e.g., altruism) was the most commonly reported motivator and fear (e.g., fainting, needles) was the most commonly reported barrier. Donation behavior was unrelated to reported motivators, but was significantly related to four reported barriers including fear of fainting/dizziness, fear of needles/pain, having personal commitments that conflict with donating, and perceiving oneself as unsuited to donate for health reasons. Sex, racial, and ethnic differences were noted with respect to the percentages of donors reporting several donation-related motivators and barriers. CONCLUSION: The present findings identify donation-related barriers that could be important targets to address in the effort to encourage new young donors and to retain these new donors for the long term. Importantly, these data also highlight the importance of considering individual differences in donor motivation as a function of sex, race, and ethnicity.

Prevalence, characteristics, and longer-term outcomes of patients with persistent critical illness attributable to COVID-19 in Scotland: a national cohort study.

BACKGROUND: Patients with COVID-19 can require critical care for prolonged periods. Patients with persistent critical Illness can have complex recovery trajectories, but this has not been studied for patients with COVID-19. We examined the prevalence, risk factors, and long-term outcomes of critically ill patients with COVID-19 and persistent critical illness. METHODS: This was a national cohort study of all adults admitted to Scottish critical care units with COVID-19 from March 1, 2020 to September 4, 20. Persistent critical illness was defined as a critical care length of stay (LOS) of ≥10 days. Outcomes included 1-yr mortality and hospital readmission after critical care discharge. Fine and Gray competing risk analysis was used to identify factors associated with persistent critical Illness with death as a competing risk. RESULTS: A total of 2236 patients with COVID-19 were admitted to critical care; 1045 patients were identified as developing persistent critical Illness, comprising 46.7% of the cohort but using 80.6% of bed-days. Patients with persistent critical illness used more organ support, had longer post-critical care LOS, and longer total hospital LOS. Persistent critical illness was not significantly associated with long-term mortality or hospital readmission. Risk factors associated with increased hazard of persistent critical illness included age, illness severity, organ support on admission, and fewer comorbidities. CONCLUSIONS: Almost half of all patients with COVID-19 admitted to critical care developed persistent critical illness, with high resource use in critical care and beyond. However, persistent critical illness was not associated with significantly worse long-term outcomes compared with patients who were critically ill for shorter periods.

State-related neural influences on fMRI connectivity estimation.

The spatiotemporal structure of functional magnetic resonance imaging (fMRI) signals has provided a valuable window into the network underpinnings of human brain function and dysfunction. Although some cross-regional temporal correlation patterns (functional connectivity; FC) exhibit a high degree of stability across individuals and species, there is growing acknowledgment that measures of FC can exhibit marked changes over a range of temporal scales. Further, FC can co-vary with experimental task demands and ongoing neural processes linked to arousal, consciousness and perception, cognitive and affective state, and brain-body interactions. The increased recognition that such interrelated neural processes modulate FC measurements has raised both challenges and new opportunities in using FC to investigate brain function. Here, we review recent advances in the quantification of neural effects that shape fMRI FC and discuss the broad implications of these findings in the design and analysis of fMRI studies. We also discuss how a more complete understanding of the neural factors that shape FC measurements can resolve apparent inconsistencies in the literature and lead to more interpretable conclusions from fMRI studies.

Improving holographic particle characterization by modeling spherical aberration.

Holographic microscopy combined with forward modeling and inference allows colloidal particles to be characterized and tracked in three dimensions with high precision. However, current models ignore the effects of optical aberrations on hologram formation. We investigate the effects of spherical aberration on the structure of single-particle holograms and on the accuracy of particle characterization. We find that in a typical experimental setup, spherical aberration can result in systematic shifts of about 2% in the inferred refractive index and radius. We show that fitting with a model that accounts for spherical aberration decreases this aberration-dependent error by a factor of two or more, even when the level of spherical aberration in the optical train is unknown. With the new generative model, the inferred parameters are consistent across different levels of aberration, making particle characterization more robust.

High-dose proton therapy and tomotherapy for the treatment of sacral chordoma: a retrospective monocentric study.

OBJECTIVE: Radiation therapy (RT) is used for the treatment of sacral chordoma, in combination with surgery or alone for unresected tumours, to improve local control (LC) and potentially overall survival (OS). The purpose of the present study was to evaluate efficacy and toxicity of proton therapy (PT), and/or intensity modulated radiation therapy (IMRT), particularly Tomotherapy, for sacral chordoma treatment. Material: Between November 2005 and June 2018, 41 consecutive patients who were not included in clinical trials, received sacral chordoma radiation treatment in Institut Curie with Tomotherapy alone in 13 patients, and combined PT and Tomotherapy boost (Proton - Tomo) in 28 patients. RT was delivered as the exclusive local treatment in 11 patients, and as a post-operative complementary treatment in 30 patients. RESULTS: After a median follow-up of 46 months (range, 0-125 months), eight local relapses were observed, and seven patients developed distant metastasis (particularly bone and lung). The 2- and 5- year local relapse rates were 11.4% CI (0.65-22.2%) and 29% (10.5-47.4%), respectively. Over the follow-up period, ten patients died (24.4%). The estimated 2- and 5-year OS rates were 91.4% CI (82.5-100%) and 74.5% (59.4-93.5%), respectively. Fibrosis, cauda equina syndrome, and pain were the most common late toxicities. The comparison between Tomotherapy alone and Proton - Tomo revealed that acute and late cystitis were significantly more frequent in the Tomotherapy group: SHR = 0.12 IC95% (0.01-0.90 [p = .04]), as well as late proctitis. A dosimetric comparison confirmed the interest of PT to spare rectum and bladder in this context. CONCLUSION: RT remains essential to improve local control in sacral chordoma. The combination of proton and photon seems to improve organ at risk sparing, resulting in a decreased rate of reported late toxicities.