Levothyroxine for a high-normal TSH in unexplained infertility.

OBJECTIVE: Unexplained infertility affects nearly one-third of infertile couples. Women with unexplained infertility are more likely to have a high-normal thyroid-stimulating hormone level (TSH: 2.5-5 mIU/L) compared to women with severe male factor infertility. Practice guidelines vary on whether treatment should be initiated for TSH levels >2.5 mIU/L in women attempting conception because the effects of treating a high-normal TSH level with levothyroxine are not known. We evaluated conception and live birth rates in women with unexplained infertility and high-normal TSH levels. DESIGN, PATIENTS AND MEASUREMENTS: Retrospective study including 96 women evaluated for unexplained infertility at a large academic medical centre between 1 January 2000 and 30 June 2017 with high-normal TSH (TSH: 2.5-5 mIU/L and within the normal range of the assay) who were prescribed (n = 31) or not prescribed (n = 65) levothyroxine. Conception and live birth rates were assessed. RESULTS: The conception rate in the levothyroxine group was 100% compared to 90% in the untreated group (p = .086 unadjusted; p < .05 adjusted for age; p = .370 adjusted for TSH; p = .287 adjusted for age and TSH). The live birth rate was lower in the levothyroxine group (63%) compared to the untreated group (84%) (p = .05 unadjusted; p = .094 adjusted for age; p = .035 adjusted for TSH; p = .057 adjusted for age and TSH). CONCLUSIONS: Women with unexplained infertility and high-normal TSH levels treated with levothyroxine had a higher rate of conception but lower live birth rate compared to untreated women, with the limitation of a small sample size. These findings assert the need for prospective, randomized studies to determine whether treatment with levothyroxine in women with unexplained infertility and high-normal TSH is beneficial.

Flexible seamless 2-in-1 design with sample size adaptation.

The 2-in-1 design is becoming popular in oncology drug development, with the flexibility in using different endpoints at different decision time. Based on the observed interim data, sponsors can choose to seamlessly advance a small phase 2 trial to a full-scale confirmatory phase 3 trial with a pre-determined maximum sample size or remain in a phase 2 trial. While this approach may increase efficiency in drug development, it is rigid and requires a pre-specified fixed sample size. In this paper, we propose a flexible 2-in-1 design with sample size adaptation, while retaining the advantage of allowing an intermediate endpoint for interim decision-making. The proposed design reflects the needs of the recent FDA's Project FrontRunner initiative, which encourages the use of an earlier surrogate endpoint to potentially support accelerated approval with conversion to standard approval with long-term endpoints from the same randomized study. Additionally, we identify the interim decision cut-off to allow a conventional test procedure at the final analysis. Extensive simulation studies showed that the proposed design requires much a smaller sample size and shorter timeline than the simple 2-in-1 design, while achieving similar power. We present a case study in multiple myeloma to demonstrate the benefits of the proposed design.

Identifying associations of de novo noncoding variants with autism through integration of gene expression, sequence and sex information.

Whole-genome sequencing (WGS) data is facilitating genome-wide identification of rare noncoding variants, while elucidating their roles in disease remains challenging. Towards this end, we first revisit a reported significant brain-related association signal of autism spectrum disorder (ASD) detected from de novo noncoding variants attributed to deep-learning and show that local GC content can capture similar association signals. We further show that the association signal appears driven by variants from male proband-female sibling pairs that are upstream of assigned genes. We then develop Expression Neighborhood Sequence Association Study (ENSAS), which utilizes gene expression correlations and sequence information, to more systematically identify phenotype-associated variant sets. Applying ENSAS to the same set of de novo variants, we identify gene expression-based neighborhoods showing significant ASD association signal, enriched for synapse-related gene ontology terms. For these top neighborhoods, we also identify chromatin states annotations of variants that are predictive of the proband-sibling local GC content differences. Our work provides new insights into associations of non-coding de novo mutations in ASD and presents an analytical framework applicable to other phenotypes.

Early Ventilator Management for Infants With Congenital Diaphragmatic Hernia: Impact of a Standardized Clinical Practice Guideline.

BACKGROUND: Infants with congenital diaphragmatic hernia (CDH) experience high morbidity and mortality due to pulmonary arterial hypertension and hypoplasia. Mechanical ventilation is a central component of CDH management. Our objective was to evaluate the impact of a standardized clinical practice guideline (implemented in January 2012) on ventilator management for infants with CDH, and associate management changes with short-term outcomes, specifically extracorporeal membrane oxygenation (ECMO) utilization and survival to discharge. METHODS: We conducted a retrospective pre-post study of 103 CDH infants admitted from January 2007-July 2021, divided pre- (n = 40) and post-guideline (n = 63). Clinical outcomes, ventilator settings, and blood gas values in the first 7 days of mechanical ventilation were compared between the pre- and post-guideline cohorts. RESULTS: Post-guideline, ECMO utilization decreased (11% vs 38%, p = 0.001) and survival to discharge improved (92% vs 68%, p = 0.001). More post-guideline patients remained on conventional mechanical ventilation without need for escalation to high-frequency ventilation or ECMO, and had higher pressures and PaCO2 with lower FiO2 and PaO2 (p < 0.05). CONCLUSIONS: Standardized ventilator management optimizing pressures for adequate lung expansion and minimizing oxygen toxicity improves outcomes for infants with CDH. LEVEL OF EVIDENCE: III.

Corticosteroid Injection in the Operative Hand Prior to a Trigger Finger or Carpal Tunnel Release: If It Is Not at the Surgical Site Then What Is the Big Deal?

BACKGROUND: Patients who have had a corticosteroid injection at the surgical site within 90 days of trigger finger release (TFR) or carpal tunnel release (CTR) have an elevated risk of postoperative infection. Currently, it remains unknown if a preoperative injection in proximity to the surgical site for a separate complaint alters the risk of a postoperative infection. METHODS: A retrospective chart review was performed on all patients who underwent TFR or CTR between 2010 and 2022. Patients who had a corticosteroid injection at or near the surgical site within 90 days of surgery were included. Outcome measures included uncomplicated healing, superficial infection requiring antibiotics, and deep infection (DI) requiring surgical debridement. RESULTS: There were 564 cases in which a corticosteroid injection was performed within 90 days of TFR or CTR. Superficial infections occurred in 12 (2.1%), and DIs occurred in 6 (1.1%) cases. There was no significant difference in infection rates between the two groups relative to the location of the injection nor timing of the injection (0-30, 31-60, or 61-90 days prior to surgery). CONCLUSIONS: Patients who had an injection at the surgical site within 90 days of TFR or CTR had an elevated rate of postoperative infection compared with published rates in the literature. This study is unique in that preoperative injections at an adjacent site in the palm also correlated with an elevated rate of infection, similar to patients who had an injection at the surgical site. LEVEL OF EVIDENCE: Level 4.

Spinning a Liquid Wheel and Driving Surface Thermomagnetic Convection with Light.

A typical Tesla thermomagnetic engine employs a solid magnetic wheel to convert thermal energy into mechanical energy, while thermomagnetic convection in ferrofluid is still challenging to observe because it is a volume convection that occurs in an enclosed space. Using a water-based ferrofluid, a liquid Tesla thermomagnetic engine is demonstrated and reports the observation of thermomagnetic convection on a free surface. Both types of fluid motions are driven by light and observed by simply placing ferrofluid on a cylindrical magnet. The surface thermomagnetic convection on the free surface is made possible by eliminating the Marangoni effect, while the spinning of the liquid wheel is achieved through the solid-like behavior of the ferrofluid under a strong magnetic field. Increasing the magnetic field reveals a transition from simple thermomagnetic convection to a combination of the central spin of the spiky wheel surrounded by thermomagnetic convection in the outer region of the ferrofluid. The coupling between multiple ferrofluid wheels through a fluid bridge is further demonstrated. These demonstrations not only unveil the unique properties of ferrofluid but also provide a new platform for studying complex fluid dynamics and thermomagnetic convection, opening up exciting opportunities for light-controlled fluid actuation and soft robotics.

Impact of colocated behavioral health on OB-GYN clinicians' rate of perinatal behavioral health diagnosis and psychotropic prescription.

OBJECTIVE: To examine the association of colocated behavioral health(BH) care with rates of OB-GYN clinician coding of BH diagnoses and BH medications. METHOD: Using 2 years of EMR data from perinatal individuals treated across 24 OB-GYN clinics, we tested the hypothesis that colocated BH care would increase rates of OB-GYN BH diagnoses and psychotropic prescription. RESULTS: Psychiatrist integration(0.1 FTE) was associated with 45.7% higher odds of OB-GYN coding for BH diagnoses and BH clinician integration was associated with 25% lower odds of OB-GYN BH diagnosis and 37.7% lower odds of BH medication prescription. Non-white patients had 28-74% and 43-76% lower odds of having a BH diagnosis and a BH medication ordered, respectively. The most common diagnoses were anxiety and depressive disorders(60%) and the most prescribed BH medications were SSRIs(86%). CONCLUSIONS: OB-GYN clinicians made fewer BH diagnoses and prescribed fewer psychotropics after 2.0 FTE BH clinician integration, a possible indication of external referrals for BH treatment. Non-white patients received BH diagnoses and medications less often than white patients. Future research in real world implementation of BH integration in OB-GYN clinics should examine fiscal strategies that support BH care manager-OB-GYN collaboration as well as methods to ensure equitable delivery of BH care.

Fracture patterns, associated injuries, management, and treatment outcomes of 530 pediatric mandibular fractures.

BACKGROUND: Mandibular fractures account for up to 48.8% of pediatric facial fractures; however, there are a wide range of available treatment modalities, and few studies describe trends in adverse outcomes of these injuries. This study describes fracture etiology, pattern, management, and treatment outcomes in pediatric mandibular fracture patients. METHODS: A retrospective review was performed of patients under 18 years of age who were evaluated for mandibular fractures at a pediatric level I trauma center between 2006 and 2021. Variables studied included demographics, etiology, medical history, associated facial fractures, other associated injuries, treatments, and outcomes. RESULTS: A total of 530 pediatric patients with 829 mandibular fractures were included in the analysis. Most isolated mandibular fractures were treated with physical therapy (PT) and rest (n=253, 47.7%). Patients with combination fractures, specifically those involving the parasymphysis and angle, were 2.63 times more likely to undergo surgical management compared to patients with a single facial fracture (p<0.0001). Older age (p<0.001), gender (p=0.042), mechanism (p=0.008) and cause of injury (p=0.002), as well as specific fractures (e.g., isolated angle (p=0.001)) were more associated with adverse outcomes. The odds of adverse outcomes were higher for patients treated with CREF or ORIF compared to conservative management (OR=1.8; 95% Cl 1.0-3.2 and OR=2.1; 95% Cl 1.2-3.5, respectively). CONCLUSION: Fracture type, mechanism of injury, and treatment modality in pediatric mandibular fractures are associated with distinct rates and types of adverse outcomes. Large scale studies characterizing these injuries are critical for guiding physicians in the management of these patients.

Longitudinal cognitive evaluation before and after delivery among people with preeclampsia.

BACKGROUND: Cognitive impairments related to preeclampsia after pregnancy have been reported; however, it is not known if weaknesses in cognition occur before and shortly after delivery. OBJECTIVE: This study aimed to assess the feasibility of longitudinal cognitive testing before and after delivery, and to investigate whether those with preeclampsia have cognitive weaknesses during the third trimester of pregnancy and at 1 and 3 months postpartum. We hypothesized that people with preeclampsia would have lower cognition scores across all time points compared with normotensive people. STUDY DESIGN: This longitudinal, prospective, observational study in a single institution enrolled people (N=30) at ≥28 weeks of gestation with preeclampsia (N=16) or normotension (N=14). People with chronic hypertension, neurologic or developmental disabilities, moderate or severe depression or anxiety, or current substance use were excluded. Subjective (Everyday Cognition Scale) and objective assessment of executive function (Stroop Color-Word Interference Test, Trail-Making Test), attention and working memory (Digit Span subtest), and information processing speed (Digit Symbol Substitution Test) was conducted, and Z-scores were calculated. Baseline characteristics (eg, prepregnancy body mass index) were collected from the medical record. Generalized linear models were used to estimate associations. RESULTS: We enrolled 37% (30/81) of eligible people and retained 80% (24/30) and 53% (16/30) at 1 and 3 months postpartum, respectively. People with preeclampsia reported more memory problems (ß=0.87; 95% confidence interval, 0.44-1.31), and scored worse on attention and working memory (ß=-0.94; 95% confidence interval, -1.42 to -0.45) and executive function (Stroop test ß=-0.86; 95% confidence interval, -1.53 to -0.19) domains compared with normotensive people after adjusting for time, age, education, and prepregnancy body mass index. CONCLUSION: Longitudinal assessment of cognition in pregnant preeclamptic and normotensive people is feasible. People with preeclampsia reported worse subjective memory and had lower scores in attention, working memory, and executive function.

Reassessing the optimal volume for malignancy detection in serous fluid cytology.

BACKGROUND: The international system for reporting serous fluid cytopathology (TIS) recommends submitting at least 50-75 mL of serous fluid to decrease false-negative results. However, prior studies did not agree on specific volume requirements or consensus adequacy criteria. Our study aims to assess whether fluid volume affects the adequacy rate and to assess the minimum volume necessary for optimal adequacy in pleural and peritoneal fluids. METHODS: A total of 8530 serous fluid cytology cases were identified in the laboratory information system. Differences in mean fluid volume received in the laboratory were compared using an ANOVA Games-Howell test based on TIS category. The percentage of malignant diagnoses across the volume ranges of 0 to 5 mL, 5 to 10 mL, 10 to 25 mL, 25 to 50 mL, 50 to 75 mL, 75 to 100 mL, 100 to 150 mL, 150 to 250 mL, 250 to 500 mL, 500 to 2000 mL was compared in pleural and peritoneal fluids using a chi-square test, and a SiZer analysis was performed. RESULTS: Mean fluid volume in inadequate, atypical, and negative cases was significantly lower compared to positive cases. A SiZer analysis showed a positive relationship between the malignancy fraction of pleural and peritoneal fluids and fluid volume. The percentage of malignant diagnoses in pleural and peritoneal fluid samples increased significantly up to a volume range of 75-100 mL. CONCLUSIONS: There is a significant relationship between fluid volume, adequacy and detection of malignancy in serous effusion cytopathology. The malignancy fraction increases with larger fluid volumes but at least 75-100 mL of fluid should be submitted for optimal diagnosis of malignancy in pleural and peritoneal fluids.

MRI as First Line Imaging for Suspected Acute Appendicitis during Pregnancy: Diagnostic Accuracy and level of Inter-Radiologist Agreement.

OBJECTIVE: Evaluation of acute appendicitis (AA) in pregnancy is supported with diagnostic imaging. Typically, ultrasound (US) is performed first, and then often followed by magnetic resonance imaging (MRI) due to continued diagnostic uncertainty. The purpose of our study was to evaluate the sensitivity, specificity, and accuracy of US as compared to MRI and to evaluate the inter-radiologist agreement amongst body Radiologists with varying levels of expertise. MATERIALS AND METHODS: We performed a retrospective study of 364 consecutive pregnant patients with clinical suspicion of AA at a single center over a 6-year period. Sensitivity, Specificity, accuracy, positive and negative predictive values were calculated for US and MRI. Inter Radiologist agreement was determined using Cohen's Kappa analysis between original interpreting Radiologist and retrospective review by expert Radiologist. RESULTS: Thirty-one of 364 patients (8.5%) underwent appendectomy based on preoperative diagnosis, with confirmation of acute appendicitis (AA) by pathology in 19. US was able to visualize the appendix in only 6 (1.65%), 5 of whom had appendicitis. 141 patients underwent MRI, and correctly diagnosed appendicitis in 9. No patient with a negative MRI diagnosis had AA. The sensitivity, and negative predictive value for diagnosing AA with MRI was 100%. The MRI inter-reader agreement for appendix visualization and overall accuracy were 87.9 and 98% with Cohen Kappa of 0.7 and 0.56 respectively. CONCLUSIONS: Our data suggests that MRI should be considered the first line imaging modality in pregnant patients suspected of having AA. Body Radiologists with varied levels of experience in MRI readouts had substantial agreement.

Selection and synthesization of multi-carbon source composites to enhance simultaneous nitrification-denitrification in treating low C/N wastewater.

Low carbon/nitrogen ratio (C/N) wastewater is widespread and difficult to treat. To find a resolution to this issue, this study systematically evaluated the constituents of composite solid carbon (i.e., skeletons, carbon sources and crosslinking agents), and proposed a new multi-carbon source composite S1 (MCSC.S1). The effects on nitrogen removal were further determined through a sequencing batch moving bed biofilm reactor (SBMBBR). The results showed that MCSC.S1, which was composed of polyvinyl alcohol-sodium alginate (PVA-SA), corncob + poly (R-ß-hydroxybutyrate) (CC + PHB), and H3BO3-4% CaCl2+Na2SO4 had high stability and absorption. With MCSC.S1, total nitrification removal was enhanced by more than 48.56% through releasing carbon and absorbing the attached denitrifying bacteria. In addition, it was found that MCSC.S1 can simulate the simultaneous nitrification and denitrification (SND) process and contribute to 29.85% of the total nitrogen removal. 16S gene-based analysis attributed this supplementary nitrogen removal to the enrichment of nitrification (i.e., Proteobacteria, Actinobacteria and Chloroflexi), denitrification of associated bacteria (i.e., Nitrospirota) in MCSC.S1 added reactor, and the increase in nitrogen recycling associated genes. These findings collectively demonstrate that the new MCSC.S1 could effectively enhance nitrogen removal efficiency in low C/N ratio wastewater.

Improving the performance of coupled solid carbon source biofilm carriers through pore-forming methods.

Coupled solid carbon source biofilm carriers (CCBs) was usually utilized to enhance the treatment efficiency of low carbon/nitrogen (C/N) wastewater. However, current CCBs have low carbon release capacity because of its small inner mass transfer coefficient. Therefore, this study innovatively applied pore-forming methods to modify CCBs. After orthogonal selections, two porous CCBs, which were respectively prepared through circulating freezing pore-forming method (CCB2) and ammonium bicarbonate pore-forming method (CCB3), were proposed and further applied in sequencing batch moving bed biofilm reactors (SBMBBRs). The results indicated that circulating freezing pore-forming method could improve the mechanical strength and carbon source release rate of CCBs. In addition, CCB2 could significantly enhance the total nitrogen (TN) removal efficiency of SBMBBRs, when compared with the non-porous CCBs (i.e., CCB1). Further biofilm and simultaneous nitrification and denitrification (SND) rate calculation attributed this enhancement to the higher biofilm amount (i.e., 0.06 g g-1 CCB) and the higher SND rate (i.e., 33.60%). Microbial community analysis reiterated these observations that CCB2 and CCB3 could accumulate Proteobacteria, Actinobacteriota and Nitrospirota, and also stimulate nitrification and denitrification associated pathways. More importantly, the cost calculation indicated CCB2 cost only 47.37% of CCB1 and 31.34% of CCB3, showing highly economic applicability. Overall, our results collectively proved that CCBs manufactured by circulating freezing pore-forming method could provide more carbon releasing points and microorganisms attaching positions, exhibiting effectively nitrogen removal when treating low C/N wastewater.

Recognizing Human Daily Activity Using Social Media Sensors and Deep Learning.

The human daily activity category represents individual lifestyle and pattern, such as sports and shopping, which reflect personal habits, lifestyle, and preferences and are of great value for human health and many other application fields. Currently, compared to questionnaires, social media as a sensor provides low-cost and easy-to-access data sources, providing new opportunities for obtaining human daily activity category data. However, there are still some challenges to accurately recognizing posts because existing studies ignore contextual information or word order in posts and remain unsatisfactory for capturing the activity semantics of words. To address this problem, we propose a general model for recognizing the human activity category based on deep learning. This model not only describes how to extract a sequence of higher-level word phrase representations in posts based on the deep learning sequence model but also how to integrate temporal information and external knowledge to capture the activity semantics in posts. Considering that no benchmark dataset is available in such studies, we built a dataset that was used for training and evaluating the model. The experimental results show that the proposed model significantly improves the accuracy of recognizing the human activity category compared with traditional classification methods.