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Nevin Manimala Statistics

Optimal Control of Directional False Discovery Rates in Large-Scale Testing

Stat Med. 2025 Feb 28;44(5):e10329. doi: 10.1002/sim.10329.

ABSTRACT

The high-throughput biomedical technology enables measurement of thousands of gene expression levels contemporaneously. A major task in analyzing these gene expression data is to identify both over-expressed and under-expressed genes. The popular two-group models select the non-null genes without further classifying them as overexpression or underexpression. Consequently, two-group decision rules are unable to constrain the numbers of falsely discovered over-expressed or under-expressed genes respectively. We propose a general three-group model that allows dependence between the test statistics and develop a decision rule that separately controls the two types of false discoveries. We show that the optimal decision rule in our three-group model has a special monotonic structure. By making use of this monotonic structure, we can linearize the two-directional false discovery rate constraints. We prove that our decision rule optimizes the expected number of true discoveries while controlling the proportions of falsely discovered over-expressed and under-expressed genes at desired levels simultaneously. The data-driven versions of the proposed procedures are suggested, and their consistency is established. Comparisons with state-of-the-art approaches and applications to genomic studies show that our procedures work well.

PMID:39912293 | DOI:10.1002/sim.10329

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Nevin Manimala Statistics

Exploration of the covariation signal between cortical bone and dentine volumes across the upper limb bones and anterior teeth in modern humans and relevance to evolutionary anthropology

J Anat. 2025 Feb 6. doi: 10.1111/joa.14227. Online ahead of print.

ABSTRACT

Cortical bone and dentine are two mineralized tissues sharing a common embryological origin, developmental, and genetic background, distinct from those of enamel. Understanding their relationship is crucial to decipher the factors acting on their postnatal development, and shedding light on the evolutionary patterns of tissue proportions. Here, we investigate the coordinated variation between cortical bone and dentine volumes measured from arm and forearm bones (humeri, ulnae, radii) and upper anterior teeth (central incisors, lateral incisors, canines) of modern humans. Given the shared characteristics of cortical bone and dentine, we expect similarities in their postnatal development, which may lead to covariation between their volumes. The degree of bone-dentine covariation may be influenced by the physiological response of upper limb bones to mechanical loading. No such covariation is expected with enamel volumes, due to the greater developmental independence of bone and enamel. Our sample includes 55 adults of African and European ancestries from South African osteological collections. Principal component analysis of cortical thickness variation along the shafts of paired humeri, ulnae, and radii is used to assess asymmetry. Bone regions with bilateral asymmetry in cortical bone thickness are considered sensitive to functional loads, while regions with minimal bilateral variation likely reflect genetic influences during bone postnatal development. Statistical analyses reveal strong positive correlations between cortical bone and dentine volumes across all bones and teeth, and weaker correlations between cortical bone and enamel. We outline a complex pattern of bone-dentine covariation that varies by skeletal location and tooth type. Contrary to our expectations, the presumed functional sensitivity of bone regions does not influence the covariation signal. Additionally, the strength of the covariation appears to align with the developmental sequence of the anterior teeth, with the upper canines showing the strongest correlation with cortical bone volumes, followed by lateral and central incisors. These results provide insights into the functional and biological factors influencing the coordinated variation of cortical bone and dentine volumes during postnatal development. Further research on the cortical bone-dentine covariation across different skeletal parts, including lower limb elements, would enhance our understanding of the effects of both endogenous and exogenous factors on the development of the mineralized tissues.

PMID:39912285 | DOI:10.1111/joa.14227

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Nevin Manimala Statistics

Post Transplant Outcomes of High-Risk Neuroblastoma From a Tertiary Care Unit in India

Indian Pediatr. 2025 Feb 15;62(2):148-150. doi: 10.1007/s13312-025-3381-7.

ABSTRACT

The management of high-risk neuroblastoma has dismal outcomes in low-and-middle-income countries (LMICs). There is limited data on post transplant outcomes of high-risk neuroblastoma from LMICs. We report the outcomes of twelve patients with high-risk neuroblastoma who underwent autologous stem cell transplanatation (ASCT) at a single tertiary care center in Northen India. At a median follow-up of 25.5 months, the event-free survival was 63.6%. Relapse occurred in four patients (33.3%), who subsequently died. All patients had febrile neutropenia; there was no ASCT-related mortality. Multidisciplinary therapy even with omission of dinutuximab in our cohort had acceptable outcomes.

PMID:39912276 | DOI:10.1007/s13312-025-3381-7

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Nevin Manimala Statistics

Hospital-Onset Seizures in Children Aged 3 Months to 12 Years: A Prospective Cohort Study

Indian Pediatr. 2025 Feb 15;62(2):143-147. doi: 10.1007/s13312-025-3380-8.

ABSTRACT

OBJECTIVE: To describe the clinical profile, etiology and outcome of children with hospital-onset seizures (HOS) in a tertiary care public hospital.

METHODS: In this prospective study, consecutive children aged 3 months to 12 years admitted for at least 24 hours in the Department of Pediatrics of a tertiary care public hospital between 1 February, 2021 and 15 September, 2021, were followed-up during hospital stay till death/discharge. Any child admitted within 7 days following head trauma, or admitted for seizure control during the current illness was excluded. All patients were followed up daily for the occurrence of seizures during hospital stay. Outcomes were assessed using Glasgow Outcome Scale (GOS).

RESULTS: Out of the 1050 children (635 boys), 25 (2.38%) children with a median (IQR) age of 12 (4,60) months developed seizures during the hospital stay. Seizures occurred at a median (IQR) interval of 21 hour (8 hour, 5 days) from admission; seizures progressed to status epilepticus in 3 (12%) children. Majority of those with seizures had an underlying neurological disorder/disease at admission. Majority of patients (68%) had generalized tonic-clonic seizures. After neuro-infections, metabolic derangements were the second most common etiological group for HOS (32%). A poor outcome, defined as death/severe disability as per GOS, was seen in 8 (32%) children with HOS. Children with HOS had a 2.76 times higher risk of a poor outcome as compared to those with no seizures during the hospital stay [RR (95% CI) 2.76 (1.07, 7.11), P = 0.035].

CONCLUSION: Physicians need to be aware of the risk factors for HOS in children so as to provide adequate monitoring and emergent treatment.

PMID:39912275 | DOI:10.1007/s13312-025-3380-8

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Nevin Manimala Statistics

Clinico-etiological Profile and Metabolic Complications in Pediatric Early Onset Obesity – Experience from a Tertiary Care Centre in India

Indian Pediatr. 2025 Feb 15;62(2):138-142. doi: 10.1007/s13312-025-3379-1.

ABSTRACT

OBJECTIVE: To describe the clinical and metabolic profile and associated risk factors in children with early onset obesity (presenting before five years of age). To identify features that would differentiate primary from secondary obesity in under-five children.

METHODS: A retrospective study analyzed the medical records of children diagnosed with early onset obesity between June 2015 to December 2023 to ascertain the etiological diagnosis and identify the risk predictors. Laboratory profiles and genetic studies, wherever available, were studied. Association of various factors with underlying etiology was done using standard statistical methods.

RESULTS: Out of 530 children presenting with obesity during the study period, 77 (14.5%) were aged less than 5 years. Primary obesity was found in 55 (71.4%) children. Genetic causes of obesity were confirmed in 14 (18.18%) children. Increased screen time (more than 2 hours per day) and acanthosis nigricans correlated positively with the presence of primary obesity. Additionally, a significant association was observed between the presence of obesity in parents and early onset primary obesity, indicating a combined influence of an unhealthy lifestyle and a genetic predisposition.

CONCLUSION: Primary obesity was more common in early onset obesity. Obesity in parents, excess screen time and presence of acanthosis nigricans were significantly associated with primary obesity suggesting a combination of genetic predisposition and unhealthy lifestyle as risk factors.

PMID:39912274 | DOI:10.1007/s13312-025-3379-1

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Nevin Manimala Statistics

Body Composition Analysis Using DEXA-Scan and its Correlation with Arm-Anthropometry in Childhood Acute Lymphoblastic Leukemia Survivors

Indian Pediatr. 2025 Feb 15;62(2):131-137. doi: 10.1007/s13312-025-3378-2.

ABSTRACT

OBJECTIVE: To determine the body composition in childhood acute lymphoblastic leukemia survivors (cALLS) using dual-energy x-ray absorptiometry (DEXA) and correlate the same with mid-upper-arm circumference (MUAC) and triceps-skin-fold thickness (TSFT).

METHODS: A cross-sectional study was undertaken to assess body composition in cALLS aged >7 years. Patients who were lost to follow-up after completion of therapy, had relapsed acute lymphoblastic leukemia (ALL), undergone hematopoietic stem cell transplantation and those with neurological disabilities/syndromic diagnosis were excluded. Prevalence of high-adiposity (body fat % > 85th centile), sarcopenia (lean body mass < 5th centile) and sarcopenic obesity (positive fat mass index z-score with negative fat-free mass index z-score); and demographic, therapy-related and endocrine factors were noted.

RESULTS: Fifty-nine cALLS survivors with a median (IQR) age of 66 (38, 91) months at diagnosis were analyzed. At a median (IQR) duration of 14 (3, 43) months following completion of therapy, 36 children (61%) had deranged body composition; high adiposity (n = 28; 47%), sarcopenia (n = 20; 34%), sarcopenic obesity (n = 9; 15%). Metabolic syndrome was seen in 7 (12%). Survivors with lower mean-age at diagnosis and at enrolment had high-adiposity levels and sarcopenia. Sarcopenia was seen more commonly in females, pre-pubertal children and survivors with a lower mean-interval from therapy completion. Obesity, sarcopenia and sarcopenic obesity were not significantly associated with the type of ALL, steroid dose and cranial-irradiation. High leptin levels were seen in survivors with obesity and sarcopenic obesity. MUAC and TSFT correlated well with DEXA-generated markers.

CONCLUSION: The prevalence of deranged body composition in cALLs from a single centre in Northern India was high, indicating need for early and frequent screening. MUAC and TSFT are reliable surrogate measures for body composition.

PMID:39912273 | DOI:10.1007/s13312-025-3378-2

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Nevin Manimala Statistics

Moderate to Vigorous Physical Activity Patterns and Cardiometabolic Risk Factors in Urban Indian Children

Indian Pediatr. 2025 Feb 15;62(2):121-125. doi: 10.1007/s13312-025-3375-5.

ABSTRACT

OBJECTIVE: To determine the duration of moderate to vigorous physical activity (MVPA), perceived barriers to physicaly activity and examine its association with cardiometabolic risk factors in Indian children.

METHODS: Sociodemographic data, physical activity patterns and the barriers to physical activity were collected using questionnaires, from urban children aged 6-19 years residing in Bengaluru, Karnataka. Anthropometry, body composition, blood pressure, glycated hemoglobin, and lipid profile were measured.

RESULTS: The mean (SD) age of a total of 4004 enrolled children was 13.1 (2.5) years; 17.8% were overweight/obese. The median (IQR) duration of MVPA was 7.7 (0.0, 44.1) minutes/day, with 81% (n = 3252) not meeting the MVPA recommendation, particularly girls (88.6%; n = 1980/2234). In adjusted analysis, children who did not engage in MVPA had elevated systolic blood pressure (mm Hg) [1.07 (95% CI 0.40, 1.35)] and diastolic blood pressure (mm Hg) [1.09 (95% CI 0.40, 1.77)]. Significant barriers to engaging in physical activity included time constraints due to academic work and lack of space/facilities.

CONCLUSION: Indian children do not meet the required daily MVPA recommendations; academic demands and limited access to space/facilities were significant barriers to physical activity. Children who did not engage in any form of MVPA had significantly higher blood pressure.

PMID:39912271 | DOI:10.1007/s13312-025-3375-5

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Nevin Manimala Statistics

One Milligram Versus Two Milligram Intramuscular Vitamin K to Prevent Late-Onset Hemorrhagic Disease in Young Infants: A Randomized Controlled Trial

Indian Pediatr. 2025 Feb 15;62(2):116-120. doi: 10.1007/s13312-025-3374-6.

ABSTRACT

OBJECTIVE: To compare the efficacy of a standard dose (1 mg) with 2 mg vitamin K administered by intramuscular (IM) route in reducing subclinical late-onset vitamin K deficiency bleeding (VKDB) assessed using serum protein induced by vitamin K absence (PIVKA II) levels.

METHODS: This was an open-labeled randomized controlled trial that enrolled healthy term neonates delivered vaginally. Neonates delivered to mothers receiving antiepileptics, anti-tuberculous drugs, or warfarin, and those with a family history of bleeding disorder were excluded. Participants were randomized to receive either 1 or 2 mg of vitamin K1 (Phytomenadione) IM at birth. PIVKA II was measured in the cord blood and at 30 and 72 days after birth by ELISA method. PIVKA II level >100 ng/mL was labeled as subclinical VKDB.

RESULTS: Forty-one neonates were recruited in each arm. On the 30 days follow-up visit 9 infants (4 in 1 mg group; 5 in 2 mg group) were lost to follow-up. All babies had PIVKA II levels >100 ng/mL at birth. The median PIVKA II values (ng/mL) in the 1 mg group were 827.68 (cord blood), 678.80 (30 days), and 644.10 (72 days). The corresponding levels (ng/mL) in the 2 mg group were higher, viz., 770.55, 726.35, and 693.14 ng/mL; P > 0.05 for all comparisons. PIVKA II level in the 1 mg group reduced significantly on 72 days of life compared to that observed at birth (cord blood) (P = 0.012). However, the fall in 2 mg group was not statistically significant.

CONCLUSION: There was no difference in PIVKA II levels between neonates receiving 1 mg or 2 mg vitamin K IM suggesting a similar risk for late-onset VKDB in both groups.

PMID:39912270 | DOI:10.1007/s13312-025-3374-6

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Nevin Manimala Statistics

Influence of Mother-Father Relationship on Perceived Stress among Black Pregnant Women

West J Nurs Res. 2025 Feb 6:1939459251316810. doi: 10.1177/01939459251316810. Online ahead of print.

ABSTRACT

BACKGROUND: Perceived stress during pregnancy has been associated with adverse maternal health and birth outcomes. Compared to White pregnant women, Black pregnant women in the United States report higher levels of perceived stress and experience higher rates of maternal mortality and preterm birth. Mother-father relationship has been associated with perceived stress among pregnant women, though literature among Black pregnant women is limited.

OBJECTIVE: We aimed to examine the associations of mother-father relationship with perceived stress among Black pregnant women.

METHODS: Using a cross-sectional, correlational design, we conducted a secondary analysis of data obtained from 418 Black pregnant women enrolled in the Biosocial Impact on Black Births study. Participants completed questionnaires between 19- and 29 weeks gestation with items related to maternal characteristics, measures of the mother-father relationship, including the level of contact, involvement, closeness, support, and conflict with the father of the baby (FOB), and maternal perceived stress.

RESULTS: Participants who reported lower levels of support (ρ[416] = -0.279, P < .001) and higher levels of conflict (ρ[416] = 0.401, P < .001) with the FOB also reported higher levels of perceived stress. Levels of involvement, closeness, support, and conflict with FOB also predicted levels of maternal perceived stress after controlling for covariates.

CONCLUSIONS: These findings suggest that the mother-father relationship significantly influences perceived stress among Black pregnant women, thus warranting further study and intervention.

PMID:39912262 | DOI:10.1177/01939459251316810

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Nevin Manimala Statistics

Measuring the Swimming Skills of Adults Attending Swimming Lessons in Australia as a Drowning Prevention Measure

Health Promot J Austr. 2025 Apr;36(2):e70010. doi: 10.1002/hpja.70010.

ABSTRACT

INTRODUCTION: Swimming and water safety skills are essential for reducing drowning. Swimming and water safety programs primarily focus on children, despite adults accounting for over 80% of fatal drowning in Australia. This study aims to identify types of adult swimming programs in Australia, who attends these programs, and measure their swimming skill achievement against national benchmarks.

METHODS: A retrospective cross-sectional study of adults attending swimming programs between 2018 and 2021 was conducted. Participant assessment records were analysed against the [Australian] National Swimming and Water Safety Framework and national benchmarks to be achieved by 6 and 12 years old. Descriptive statistics and Chi-square analysis were undertaken.

RESULTS: Of 4914 adults attending swimming lessons, 44% were female, median age was 38 years, and 40% were from high socioeconomic areas. On average, adults attended nine lessons, averaging 4.5 h in the water. At their final assessment, 69% could swim at least 5 m (6-year-old benchmark), and 8% could swim 50 m continuously (12-year-old benchmark).

CONCLUSIONS: Adults of all ages are learning to swim; however, only 8% are achieving the 12-year-old benchmark of swimming 50 m. An equity issue exists, with adults from lower socioeconomic areas and men less likely to be attending swimming programs. Developing and maintaining water safety skills throughout the lifespan is vital for reducing drowning risk among adults. SO WHAT?: Adults are spending time, money and effort learning to swim, however, more is needed to ensure that participants stay in lessons long enough to develop the necessary skills needed to be safe in the water.

PMID:39912253 | DOI:10.1002/hpja.70010