Tag: nevin manimala

PLoS Comput Biol. 2021 May 12;17(5):e1008958. doi: 10.1371/journal.pcbi.1008958. Online ahead of print.

ABSTRACT

The dynamics of local cortical networks are irregular, but correlated. Dynamic excitatory-inhibitory balance is a plausible mechanism that generates such irregular activity, but it remains unclear how balance is achieved and maintained in plastic neural networks. In particular, it is not fully understood how plasticity induced changes in the network affect balance, and in turn, how correlated, balanced activity impacts learning. How do the dynamics of balanced networks change under different plasticity rules? How does correlated spiking activity in recurrent networks change the evolution of weights, their eventual magnitude, and structure across the network? To address these questions, we develop a theory of spike-timing dependent plasticity in balanced networks. We show that balance can be attained and maintained under plasticity-induced weight changes. We find that correlations in the input mildly affect the evolution of synaptic weights. Under certain plasticity rules, we find an emergence of correlations between firing rates and synaptic weights. Under these rules, synaptic weights converge to a stable manifold in weight space with their final configuration dependent on the initial state of the network. Lastly, we show that our framework can also describe the dynamics of plastic balanced networks when subsets of neurons receive targeted optogenetic input.

PMID:33979336 | DOI:10.1371/journal.pcbi.1008958

PLoS One. 2021 May 12;16(5):e0250266. doi: 10.1371/journal.pone.0250266. eCollection 2021.

ABSTRACT

Black and Latinx students are underrepresented on most public university campuses. At the same time, affirmative action policies are controversial and legally fraught. The Supreme Court has ruled that affirmative action should help a minoritized group achieve a critical mass of representation. While the idea of critical mass is frequently invoked in law and in policy, the term remains ill-defined and hence difficult to operationalize. Motivated by these challenges, we build a mathematical model to forecast undergraduate student body racial/ethnic demographics on public university campuses. Our model takes the form of a Markov chain that tracks students through application, admission, matriculation, retention, and graduation. Using publicly available data, we calibrate our model for two different campuses within the University of California system, test it for accuracy, and make a 10-year prediction. We also propose a coarse definition of critical mass and use our model to assess progress towards it at the University of California-Berkeley. If no policy changes are made over the next decade, we predict that the Latinx population on campus will move towards critical mass but not achieve it, and that the Black student population will decrease, moving further below critical mass. Because affirmative action is banned in California and in nine other states, it is worthwhile to consider alternative policies for diversifying a campus, including targeted recruitment and retention efforts. Our modeling framework provides a setting in which to test the efficacy of affirmative action and of these alternative policies.

PMID:33979324 | DOI:10.1371/journal.pone.0250266

PLoS Biol. 2021 May 12;19(5):e3001215. doi: 10.1371/journal.pbio.3001215. Online ahead of print.

ABSTRACT

Perceptual anomalies in individuals with autism spectrum disorder (ASD) have been attributed to an imbalance in weighting incoming sensory evidence with prior knowledge when interpreting sensory information. Here, we show that sensory encoding and how it adapts to changing stimulus statistics during feedback also characteristically differs between neurotypical and ASD groups. In a visual orientation estimation task, we extracted the accuracy of sensory encoding from psychophysical data by using an information theoretic measure. Initially, sensory representations in both groups reflected the statistics of visual orientations in natural scenes, but encoding capacity was overall lower in the ASD group. Exposure to an artificial (i.e., uniform) distribution of visual orientations coupled with performance feedback altered the sensory representations of the neurotypical group toward the novel experimental statistics, while also increasing their total encoding capacity. In contrast, neither total encoding capacity nor its allocation significantly changed in the ASD group. Across both groups, the degree of adaptation was correlated with participants’ initial encoding capacity. These findings highlight substantial deficits in sensory encoding-independent from and potentially in addition to deficits in decoding-in individuals with ASD.

PMID:33979326 | DOI:10.1371/journal.pbio.3001215

PLoS Med. 2021 May 12;18(5):e1003642. doi: 10.1371/journal.pmed.1003642. Online ahead of print.

ABSTRACT

BACKGROUND: Depression is recognized globally as a leading cause of disability. Early-life adverse childhood experiences (ACEs) have been shown to have robust associations with poor mental health during adulthood. These effects may be cumulative, whereby a greater number of ACEs are progressively associated with worse outcomes. This study aimed to estimate the associations between ACEs and adult depression and suicidal ideation in a cross-sectional, population-based study of adults in Uganda.

METHODS AND FINDINGS: Between 2016 and 2018, research assistants visited the homes of 1,626 adult residents of Nyakabare Parish, a rural area in southwestern Uganda. ACEs were assessed using a modified version of the Adverse Childhood Experiences-International Questionnaire, and depression symptom severity and suicidal ideation were assessed using the Hopkins Symptom Checklist for Depression (HSCL-D). We applied a validated algorithm to determine major depressive disorder diagnoses. Overall, 1,458 participants (90%) had experienced at least one ACE, 159 participants (10%) met criteria for major depressive disorder, and 28 participants (1.7%) reported suicidal ideation. We fitted regression models to estimate the associations between cumulative number of ACEs and depression symptom severity (linear regression model) and major depressive disorder and suicidal ideation (Poisson regression models). In multivariable regression models adjusted for age, sex, primary school completion, marital status, self-reported HIV status, and household asset wealth, the cumulative number of ACEs was associated with greater depression symptom severity (b = 0.050; 95% confidence interval [CI], 0.039-0.061, p < 0.001) and increased risk for major depressive disorder (adjusted relative risk [ARR] = 1.190; 95% CI, 1.109-1.276; p < 0.001) and suicidal ideation (ARR = 1.146; 95% CI, 1.001-1.311; p = 0.048). We assessed the robustness of our findings by probing for nonlinearities and conducting analyses stratified by age. The limitations of the study include the reliance on retrospective self-report as well as the focus on ACEs that occurred within the household.

CONCLUSIONS: In this whole-population, cross-sectional study of adults in rural Uganda, the cumulative number of ACEs had statistically significant associations with depression symptom severity, major depressive disorder, and suicidal ideation. These findings highlight the importance of developing and implementing policies and programs that safeguard children, promote mental health, and prevent trajectories toward psychosocial disability.

PMID:33979329 | DOI:10.1371/journal.pmed.1003642

Transplantation. 2021 May 11. doi: 10.1097/TP.0000000000003815. Online ahead of print.

ABSTRACT

BACKGROUND: Acute rejection (AR) and recurrent HCV (R-HCV) are significant complications in liver allograft recipients. Noninvasive diagnosis of intragraft pathologies may improve their management.

METHODS: We performed small RNA sequencing and miRNA microarray profiling of RNA from sera matched to liver allograft biopsies from patients with nonimmune, nonviral (NINV) native liver disease. Absolute levels of informative miRNAs in 91 sera matched to 91 liver allograft biopsies were quantified using customized RT-qPCR assays: 30 biopsy-matched sera from 26 unique NINV patients and 61 biopsy-matched sera from 41 unique R-HCV patients. The association between biopsy diagnosis and miRNA abundance was analyzed by logistic regression and calculating the area under the receiver operating characteristic curve.

RESULTS: Nine miRNAs- miR-22, miR-34a, miR-122, miR-148a, miR-192, miR-193b, miR-194, miR-210 and miR-885-5p- were identified by both sRNA-seq and TLDA to be associated with NINV-AR. Logistic regression analysis of absolute levels of miRNAs and goodness-of-fit of predictors identified a linear combination of miR-34a + miR-210 (P<0.0001) as the best statistical model and miR-122 + miR-210 (P<0.0001) as the best model that included miR-122. A different linear combination of miR-34a + miR-210 (P<0.0001) was the best model for discriminating NINV-AR from R-HCV with intragraft inflammation, and miR-34a + miR-122 (P<0.0001) was the best model for discriminating NINV-AR from R-HCV with intragraft fibrosis.

CONCLUSIONS: Circulating levels of miRNAs, quantified using customized RT-qPCR assays, may offer a rapid and noninvasive means of diagnosing AR in human liver allografts and for discriminating AR from intragraft inflammation or fibrosis due to recurrent HCV.Supplemental Visual Abstract; http://links.lww.com/TP/C231.

PMID:33979314 | DOI:10.1097/TP.0000000000003815

PLoS Genet. 2021 May 12;17(5):e1009497. doi: 10.1371/journal.pgen.1009497. Online ahead of print.

ABSTRACT

Optical Coherence Tomography (OCT) enables non-invasive imaging of the retina and is used to diagnose and manage ophthalmic diseases including glaucoma. We present the first large-scale genome-wide association study of inner retinal morphology using phenotypes derived from OCT images of 31,434 UK Biobank participants. We identify 46 loci associated with thickness of the retinal nerve fibre layer or ganglion cell inner plexiform layer. Only one of these loci has been associated with glaucoma, and despite its clear role as a biomarker for the disease, Mendelian randomisation does not support inner retinal thickness being on the same genetic causal pathway as glaucoma. We extracted overall retinal thickness at the fovea, representative of foveal hypoplasia, with which three of the 46 SNPs were associated. We additionally associate these three loci with visual acuity. In contrast to the Mendelian causes of severe foveal hypoplasia, our results suggest a spectrum of foveal hypoplasia, in part genetically determined, with consequences on visual function.

PMID:33979322 | DOI:10.1371/journal.pgen.1009497

Sci Prog. 2021 Apr-Jun;104(2):368504211016938. doi: 10.1177/00368504211016938.

ABSTRACT

The study aimed to describe and analyse patient-reported recovery in patients after upper abdominal cancer surgery. This study had a quantitative design and patients were consecutively included in a university hospital in southern Sweden. Twenty-four patients answered the Postoperative Recovery Profile (PRP) questionnaire at three measurement points. All five dimensions were affected. In the physical symptoms dimension, the majority of patients reported a lack of energy upon discharge. High levels of anxiety were reported. Over 50% of patients reported some degree of depressed mood at all three measurement points. In the social dimension, the majority of patients reported some degree of being dependent on help from others in everyday life at 4 weeks after discharge. Few patients are fully recovered at 4 weeks after discharge. Individual patient-reported recovery estimates may be valuable in identifying and planning interventions tailored to each patient’s needs throughout the care process.

PMID:33979255 | DOI:10.1177/00368504211016938

Curr Med Res Opin. 2021 May 12:1. doi: 10.1080/03007995.2021.1929136. Online ahead of print.

ABSTRACT

PURPOSE: Multiple myeloma (MM) is a rare but treatable hematological cancer, which makes Health-Related Quality of Life (HRQoL) an important patient-report outcome measure in clinical studies. The Quality of Life Questionnaire Multiple Myeloma Module (QLQ-MY20) was developed by the European Organization for Research and Treatment of Cancer (EORTC) to measure HRQoL in people with MM. However, the Brazilian Portuguese version of QLQ-MY20 has not yet been validated for Brazil. This study aimed to evaluate the validity and reliability of the instrument for application in Brazilian patients with MM.

METHODS: This is a cross-sectional methodological study with patients seen in health services in Belo Horizonte, Brazil. The variables were collected through face-to-face interviews with the QLQ-MY20 instrument and complemented with data from medical records. Content validity analyses (content validity coefficient – CVC; correctness ratio), convergent and divergent validity (Spearman’s correlation coefficient – CC), internal consistency, and temporal reproducibility (test-retest; intraclass correlation coefficient – ICC) were performed.

RESULTS: 225 patients were included and 71.1% were older than 60. The analysis of the judging committee showed adequate content validity. We observed mainly a good internal consistency of the items and good discrimination power in the convergent and divergent validity. High ICC values were observed through the test-retest, and there was no difference in the scores between the two moments, which shows good temporal stability of the instrument.

CONCLUSION: The study allowed us to conclude that the Brazilian version of the QLQ-MY20 module is valid and reliable, and thus suitable for application in Brazilians living with MM.

PMID:33979261 | DOI:10.1080/03007995.2021.1929136

Clin Transl Gastroenterol. 2021 May 11;12(5):e00359. doi: 10.14309/ctg.0000000000000359.

ABSTRACT

INTRODUCTION: Urinary neutrophil gelatinase-associated lipocalin (NGAL) has shown promise in differentiating acute tubular necrosis (ATN) from other types of acute kidney injuries (AKIs) in cirrhosis, particularly hepatorenal syndrome (HRS). However, NGAL is not currently available in clinical practice in North America.

METHODS: Urinary NGAL was measured in a prospective cohort of 213 US hospitalized patients with decompensated cirrhosis (161 with AKI and 52 reference patients without AKI). NGAL was assessed for its ability to discriminate ATN from non-ATN AKI and to predict 90-day outcomes.

RESULTS: Among patients with AKI, 57 (35%) had prerenal AKI, 55 (34%) had HRS, and 49 (30%) had ATN, with a median serum creatinine of 2.0 (interquartile range 1.5, 3.0) mg/dL at enrollment. At an optimal cutpoint of 244 μg/g creatinine, NGAL distinguished ATN (344 [132, 1,429] μg/g creatinine) from prerenal AKI (45 [0, 154] μg/g) or HRS (110 [50, 393] μg/g; P < 0.001), with a C statistic of 0.762 (95% confidence interval 0.682, 0.842). By 90 days, 71 of 213 patients (33%) died. Higher median NGAL was associated with death (159 [50, 865] vs 58 [0, 191] μg/g; P < 0.001). In adjusted and unadjusted analysis, NGAL significantly predicted 90-day transplant-free survival (P < 0.05 for all Cox models) and outperformed Model for End-Stage Liver Disease score by C statistic (0.697 vs 0.686; P = 0.04), net reclassification index (37%; P = 0.008), and integrated discrimination increment (2.7%; P = 0.02).

DISCUSSION: NGAL differentiates the type of AKI in cirrhosis and may improve prediction of mortality; therefore, it holds potential to affect management of AKI in cirrhosis.

PMID:33979307 | DOI:10.14309/ctg.0000000000000359

BMJ Glob Health. 2021 May;6(5):e004398. doi: 10.1136/bmjgh-2020-004398.

ABSTRACT

INTRODUCTION: Child mortality remains highest in regions of the world most affected by HIV/AIDS. The aim of this study was to assess child mortality rates in relation to maternal HIV status from 2005 to 2015, the period of rapid HIV treatment scale-up in Rwanda.

METHODS: We used data from the 2005, 2010 and 2015 Rwanda Demographic Health Surveys to derive under-2 mortality rates by survey year and mother’s HIV status and to build a multivariable logistic regression model to establish the association of independent predictors of under-2 mortality stratified by mother’s HIV status.

RESULTS: In total, 12 010 live births were reported by mothers in the study period. Our findings show a higher mortality among children born to mothers with HIV compared with HIV negative mothers in 2005 (216.9 vs 100.7 per 1000 live births) and a significant reduction in mortality for both groups in 2015 (72.0 and 42.4 per 1000 live births, respectively). In the pooled reduced multivariable model, the odds of child mortality was higher among children born to mothers with HIV, (adjusted OR, AOR 2.09; 95% CI 1.57 to 2.78). The odds of child mortality were reduced in 2010 (AOR 0.69; 95% CI 0.59 to 0.81) and 2015 (AOR 0.35; 95% CI 0.28 to 0.44) compared with 2005. Other independent predictors of under-2 mortality included living in smaller families of 1-2 members (AOR 5.25; 95% CI 3.59 to 7.68), being twin (AOR 4.93; 95% CI 3.51 to 6.92) and being offspring from mothers not using contraceptives at the time of the survey (AOR 1.6; 95% CI 1.38 to 1.99). Higher education of mothers (completed primary school: (AOR 0.74; 95% CI 0.64 to 0.87) and secondary or higher education: (AOR 0.53; 95% CI 0.38 to 0.74)) was also associated with reduced child mortality.

CONCLUSIONS: This study shows an important decline in under-2 child mortality among children born to both mothers with and without HIV in Rwanda over a 10-year span.

PMID:33975886 | DOI:10.1136/bmjgh-2020-004398