Symptoms of Cognitive Impairment Among Children With Atopic Dermatitis.

Importance: Previous studies suggest that atopic dermatitis (AD) is associated with cognitive impairment in children, but these studies have relied primarily on neurodevelopmental diagnoses (rather than symptoms) as proxy measures of cognitive function. It remains unknown if certain subpopulations of children with AD are at greater risk of cognitive impairment. Objective: To examine the association of AD with symptoms of cognitive impairment (difficulty in learning or memory) among US children and whether this association varies according to the presence or absence of neurodevelopmental comorbidities (attention-deficit/hyperactivity disorder [ADHD], developmental delay, or learning disability). Design, Setting, and Participants: This cross-sectional study used 2021 data from the US National Health Interview Survey collected on children aged 17 years or younger without intellectual disability or autism. The presence of AD was based on a parent or adult caregiver's report indicating either a current diagnosis of AD or a previous medical confirmation of AD by a health care professional. Main Outcomes and Measures: Difficulty with learning or memory as reported by the child's caregiver. Results: Among the weighted total of 69 732 807 participants, 9 223 013 (13.2%) had AD. Compared with children without AD, children with AD were more likely to experience difficulties with learning (10.8% [95% CI, 7.8%-15.8%] vs 5.9% [95% CI, 5.1%-6.9%]; P < .001) and difficulties with memory (11.1% [95% CI, 8.0%-15.9%] vs 5.8% [95% CI, 4.9%-6.9%]; P < .001). In multivariable logistic regression models adjusted for sociodemographic factors, asthma, food allergies, and seasonal allergies or hay fever, AD was associated with increased odds of difficulties in learning (adjusted odds ratio [AOR], 1.77; 95% CI, 1.28-2.45) and memory (AOR, 1.69; 95% CI, 1.19-2.41). In analyses stratified by neurodevelopmental comorbidities, AD was associated with 2- to 3-fold greater odds of memory difficulties among children with any neurodevelopmental disorder (AOR, 2.26; 95% CI, 1.43-3.57), including ADHD (AOR, 2.90; 95% CI, 1.60-5.24) or learning disabilities (AOR, 2.04; 95% CI, 1.04-4.00). However, AD was not associated with learning or memory difficulties among children without neurodevelopmental conditions. Conclusions and Relevance: Results of this cross-sectional study suggest that pediatric AD was generally associated with greater odds of reported difficulties in learning and memory. However, this association was primarily limited to children with neurodevelopmental comorbidities, such as ADHD or learning disabilities. These findings may improve the risk stratification of children with AD for cognitive impairments and suggest that evaluation for cognitive difficulties should be prioritized among children with AD and neurodevelopmental disorders.

Antibody-drug conjugates in breast cancer: overcoming resistance and boosting immune response.

Antibody-drug conjugates (ADCs) have emerged as a revolutionary therapeutic class, combining the precise targeting ability of monoclonal antibodies with the potent cytotoxic effects of chemotherapeutics. Notably, ADCs have rapidly advanced in the field of breast cancer treatment. This innovative approach holds promise for strengthening the immune system through antibody-mediated cellular toxicity, tumor-specific immunity, and adaptive immune responses. However, the development of upfront and acquired resistance poses substantial challenges in maximizing the effectiveness of these therapeutics, necessitating a deeper understanding of the underlying mechanisms. These mechanisms of resistance include antigen loss, derangements in ADC internalization and recycling, drug clearance, and alterations in signaling pathways and the payload target. To overcome resistance, ongoing research and development efforts are focused on urgently identifying biomarkers, integrating immune therapy approaches, and designing novel cytotoxic payloads. This Review provides an overview of the mechanisms and clinical effectiveness of ADCs, and explores their unique immune-boosting function, while also highlighting the complex resistance mechanisms and safety challenges that must be addressed. A continued focus on how ADCs impact the tumor microenvironment will help to identify new payloads that can improve patient outcomes.

Cognitive functioning in children with atopic dermatitis: Pilot observations.

Atopic dermatitis (AD) is a common and chronic inflammatory skin disease that can adversely affect quality of life and carry significant burdens on physical, emotional, and social health. Recent evidence suggests that AD may also impair cognition, including attention and memory. In a pilot study of six children with AD, we administered a comprehensive battery of assessments to evaluate cognition and behavior and found that this approach was feasible and practical, which will enable the conduct of future larger-scale studies to characterize the impact of AD on cognitive function.

Flexible Flat Foot, Short Tendo-Achilles, and Altered Gait.

Background Pediatric patients often present with vague complaints involving the anterolateral foot and ankle, the medial knee, the lower back, and the hip. In our experience, closer examination of these patients reveals a constellation of symptoms that involve pathology in the ankle, knee, back, and hip. This study aimed to detail the identification and treatment of patients with the triad of flexible flat feet, tight Achilles complex, and altered gait, and their clinical course over time. Methods All patients of age 18 years or younger who presented to our urban academic center outpatient clinic with foot, ankle, patellar, low back, or hip pain or pathology were included. Patients with identified tarsal coalitions, accessory naviculars, malalignment syndrome, bone cysts or tumors, soft tissue tumors, arthropathy, neuropathy, infection, limb length inequality, patellar subluxation or dislocation, or spinal pathology were excluded. For each patient, demographic information, symptom description, treatment, and clinical course, including the Foot and Ankle Outcome Score (FAOS) was recorded. Results A total of 62 patients were included in our study. Patients mostly presented with low back pain (n=24, 38.7%), medial patellar pain (n=36, 58.1%), anterolateral ankle pain (n=35, 56.5%), and vague foot pain (n=13, 21.0%). Overall, 53.8% of patients with back pain at the initial visit, 35.0% of patients with knee pain, 44.4% of patients with ankle pain and 80.0% of patients with foot pain improved at final follow up. While patient-reported sports and recreation subscale scores demonstrated a significant improvement at the final follow-up compared to baseline scores (p=0.02), all other scores did not significantly differ compared to baseline scores. At final follow-up, 12 of 26 (46.2%) patients reported being able to return to play in their desired sport. Conclusion Complaints of back, hip, knee, ankle, or foot pain in the pediatric population can be early markers for a constellation of conditions that include low back pain, flexible flat feet, Achilles contracture, and altered gait due to increased lateral subluxation of the patella and hip flexion.

Local Anesthetic Injection Before Incision Decreases General Anesthesia Requirements in Pediatric Trigger Thumb Release: A Randomized Controlled Trial.

BACKGROUND: Animal studies have shown evidence of neurotoxicity from inhalational anesthesia, yet clinical studies have been less conclusive. While ongoing studies investigate the clinical significance of anesthesia-associated neurodevelopmental changes in young children, reducing anesthetic exposure in pediatric orthopaedic surgery is prudent. The primary objective of this study is to determine if local anesthetic injection before surgical incision versus after surgical release decreased inhalational anesthetic exposure in children undergoing unilateral trigger thumb release. The secondary objectives were to determine if the timing of local anesthetic injection affected postoperative pain or length of stay. METHODS: This was a single-center randomized controlled trial of pediatric patients (4 y and below) undergoing unilateral trigger thumb release. Subjects were randomized into preincision or postrelease local anesthesia injection groups. The surgeon was aware of the treatment group, while the anesthesiologist was blinded. Patient demographics, operative times, cumulative sevoflurane dose, and postoperative anesthesia care unit recovery characteristics were collected. The χ2, Fisher exact, and Mann-Whitney U tests were conducted. RESULTS: A total of 24 subjects were enrolled, with 13 randomized to the preincision injection group and 11 to the postprocedure injection group. There was no significant difference in age, sex, operative time, or tourniquet time between groups. There was a significant difference in the cumulative sevoflurane dose between the preincision injection group (23.2 vol%; interquartile range: 21.7 to 27.6) and the postprocedure injection group (28.1 vol%; interquartile range: 27 to 30) (P=0.03), with a 21% reduction in cumulative dose. There were no significant differences in postoperative pain scores, use of rescue pain medications, the incidence of nausea, or time to discharge between groups. CONCLUSIONS: Administering local anesthesia before incision versus at the end of the procedure significantly decreased cumulative sevoflurane dose for unilateral trigger thumb release. The results of this study suggest that local anesthetic injection before the incision is a low risk, easy method to reduce general anesthesia requirements during trigger thumb release and could decrease sevoflurane exposure more substantially in longer procedures and mitigate risks of neurotoxicity. Preincision injection with local anesthetic should be incorporated into routine clinical practice. LEVEL OF EVIDENCE: Level I.

Comparison of radiomic feature aggregation methods for patients with multiple tumors.

Radiomic feature analysis has been shown to be effective at analyzing diagnostic images to model cancer outcomes. It has not yet been established how to best combine radiomic features in cancer patients with multifocal tumors. As the number of patients with multifocal metastatic cancer continues to rise, there is a need for improving personalized patient-level prognosis to better inform treatment. We compared six mathematical methods of combining radiomic features of 3,596 tumors in 831 patients with multiple brain metastases and evaluated the performance of these aggregation methods using three survival models: a standard Cox proportional hazards model, a Cox proportional hazards model with LASSO regression, and a random survival forest. Across all three survival models, the weighted average of the largest three metastases had the highest concordance index (95% confidence interval) of 0.627 (0.595-0.661) for the Cox proportional hazards model, 0.628 (0.591-0.666) for the Cox proportional hazards model with LASSO regression, and 0.652 (0.565-0.727) for the random survival forest model. This finding was consistent when evaluating patients with different numbers of brain metastases and different tumor volumes. Radiomic features can be effectively combined to estimate patient-level outcomes in patients with multifocal brain metastases. Future studies are needed to confirm that the volume-weighted average of the largest three tumors is an effective method for combining radiomic features across other imaging modalities and tumor types.

Patterns and Results of Triage Advice Before Emergency Department Visits Made by Patients With Cancer.

PURPOSE: Patients with cancer undergoing treatment frequently visit the emergency department (ED) for commonly anticipated complaints (eg, pain, nausea, and vomiting). Nearly all Medicare Oncology Care Model (OCM) participants prioritized ED use reduction, and the OCM requires that patients have 24-hour telephone access to a clinician, but actual reductions in ED visits have been mixed. Little is known about the use of telephone triage for acute care. METHODS: We identified adults aged 18+ years newly diagnosed with cancer, linked to ED visits from a single institution within 6 months after diagnosis, and then analyzed the telephone and secure electronic messages in the preceding 24 hours. We coded interactions to classify the reason for the call, the main ED referrer, and other attempted management. We compared the acuity of patient self-referred versus clinician-referred ED visits by modeling hospitalization and ED visit severity. RESULTS: From 2011 to 2018, 3,247 adults made 5,371 ED visits to the university hospital and self-referred to the ED 58.5% of the time. Clinicians referred to outpatient or oncology urgent care for 10.3% of calls but referred to the ED for 61.3%. Patient self-referred ED visits were likely to be hospitalized (adjusted Odds Ratio [aOR], 0.89, 95% CI, 0.64 to 1.22) and were not more severe (aOR, 0.75, 95% CI, 0.55 to 1.02) than clinician referred. CONCLUSION: Although patients self-referred for six of every 10 ED visits, self-referred visits were not more severe. When patients called for advice, clinicians regularly recommended the ED. More should be done to understand barriers that patients and clinicians experience when trying to access non-ED acute care.

Comparison of Radiomic Feature Aggregation Methods for Patients with Multiple Tumors.

Background: Radiomic feature analysis has been shown to be effective at modeling cancer outcomes. It has not yet been established how to best combine these radiomic features in patients with multifocal disease. As the number of patients with multifocal metastatic cancer continues to rise, there is a need for improving personalized patient-level prognostication to better inform treatment. Methods: We compared six mathematical methods of combining radiomic features of 3596 tumors in 831 patients with multiple brain metastases and evaluated the performance of these aggregation methods using three survival models: a standard Cox proportional hazards model, a Cox proportional hazards model with LASSO regression, and a random survival forest. Results: Across all three survival models, the weighted average of the largest three metastases had the highest concordance index (95% confidence interval) of 0.627 (0.595-0.661) for the Cox proportional hazards model, 0.628 (0.591-0.666) for the Cox proportional hazards model with LASSO regression, and 0.652 (0.565-0.727) for the random survival forest model. Conclusions: Radiomic features can be effectively combined to establish patient-level outcomes in patients with multifocal brain metastases. Future studies are needed to confirm that the volume-weighted average of the largest three tumors is an effective method for combining radiomic features across other imaging modalities and disease sites.

Fluoride at waste oyster shell surfaces - Role of magnesium.

Reaction of fluoride with waste oyster shell was studied. To enhance the stability and adsorption capacity, oyster shell was coated with Al(OH)3 and the adsorption behaviors were compared with the uncoated one. When at low fluoride concentration (<30 mg/L), fluoride removal efficiency decreased with increasing pH, and the adsorption could be modeled by Langmuir isotherm. At high fluoride concentration (>100 mg/L), linear adsorption isotherm fitted better, in which the adsorption capacity of fluoride increased linearly with increasing equilibrium fluoride concentration. The coated oyster shell showed higher adsorption capacity and wider workable pH range. From XPS analysis, the presence of CaF2 was confirmed by the peak at 684.7 eV when fluoride concentration increased. It was noted that magnesium content of waste oyster shell reacted with fluoride to form significant fractions of MgF2 whose corresponding peak was detected at 685.6-685.8 eV. For coated oyster shell, fluoride reacted with Ca, Mg, and Al. The reaction mechanism was mainly adsorption at low initial concentration, and precipitation-dominated at higher concentration.

New application of dydrogesterone as a part of a progestin-primed ovarian stimulation protocol for IVF: a randomized controlled trial including 516 first IVF/ICSI cycles.

STUDY QUESTION: Can dydrogesterone (DYG) be used as an alternative progestin in a progesterone primed ovarian stimulation (PPOS) protocol? SUMMARY ANSWER: DYG can be used as an appropriate alternative progestin in a PPOS protocol. WHAT IS KNOWN ALREADY: PPOS is a new ovarian stimulation regimen based on a freeze-all strategy that uses progestin as an alternative to a GnRH analog for suppressing a premature LH surge during the follicular phase. Medroxyprogesterone acetate (MPA) has been successfully used as an adjuvant to gonadotrophin in the PPOS protocol. However, the use of MPA may lead to stronger pituitary suppression and thus may require a higher dosage of hMG and a longer duration of ovarian stimulation than that of conventional ovarian stimulation protocol. STUDY DESIGN SIZE, DURATION: A prospective RCT including 516 patients was performed between November 2015 and November 2016. Computerized randomization was conducted to assign participants at a 1:1 ratio into two treatment groups: an hMG + DYG group (260 patients) or an hMG + MPA group (256 patients) followed by IVF or ICSI with the freeze-all strategy. One cycle per patient was included. The primary outcome of the trial was the number of oocytes retrieved. The sample size was chosen to detect a difference of two oocytes with a power of 90%. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients under 36 years of age with normal ovarian reserve who were undergoing their first IVF/ICSI procedure due to tubal factor infertility were randomized into two groups based on the oral progestin protocol used: hMG co-treatment with DYG (hMG + DYG) or hMG co-treatment with MPA (hMG + MPA). The different progestin was simultaneously administered at the beginning of menstrual cycle 3 (MC3). Oocyte maturation was co-triggered by administration of a GnRH agonist and hCG. All viable embryos from both protocols were cryopreserved for later transfer. Only the first frozen embryo transfer (FET) cycle was included in our study. The embryological and clinical outcomes were measured. MAIN RESULTS AND THE ROLE OF CHANCE: Basic characteristics, such as age, BMI and infertility duration, in both groups were comparable. There was no significant difference in the number (mean ± SD) of oocytes retrieved [10.8 ± 6.3 for the hMG + DYG group versus 11.1 ± 5.8 for the hMG + MPA group, P = 0.33] or the oocyte retrieval rate [74.3 ± 19.6% for the hMG + DYG group versus 75.0 ± 19.5% for the hMG + MPA group, P = 0.69] between the groups. The viable embryo rate per oocyte retrieved did not differ between the two groups [odds ratio (OR): 1.08, 95% CI: 0.97-1.21, P = 0.16]: 37.4% (1052/2815) for the hMG + DYG group versus 35.6% (1009/2837) for the hMG + MPA group. During the whole process of ovarian stimulation, the mean LH level in the hMG + DYG group was always higher than that in the hMG + MPA group (P < 0.001); however, no patient from either group experienced a premature LH surge. In addition, no patients experienced moderate or severe ovarian hyperstimulation syndrome during the ovarian stimulation. No significant difference was found in the clinical pregnancy rate of the first FET cycle between the two groups (OR: 0.82, 95% CI: 0.56-1.21, P = 0.33): 57.6% for the hMG + DYG group (125/217) versus 62.3% for the hMG + MPA group (132/212). LIMITATIONS REASONS FOR CAUTION: The patients and physician were not blinded to the study. Further, a large proportion of patients were still pregnant at the end of the clinical trial, therefore live birth rates were not observed in the follow-up period. The dose-effectiveness of DYG administration was not addressed in the trial design. WIDER IMPLICATIONS OF THE FINDINGS: DYG, which exhibits no or only weak inhibition of ovulation in normal dosage, can serve as an hMG adjuvant during ovarian stimulation. This finding suggests the possibility of a new application of DYG: as an appropriate alternative progestin for a PPOS protocol in IVF. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by The National Nature Science Foundation of China (Grant no. 81503603), Shanghai Three-year Plan on Promoting TCM Development (Grant no. ZY3-LCPT-2-2006) and the Natural Science Foundation of Shanghai (Grant nos. 15401932700 and 15ZR1424900). None of the authors declare any conflict of interest. TRIAL REGISTRATION NUMBER: Chictr.org.cn: ChiCTR-IPR-15007251. TRIAL REGISTRATION DATE: Chictr.org.cn: 22 October 2015. DATE OF FIRST PATIENT'S ENROLLMENT: 1 November 2015.

Drug Therapy Problem Identification and Resolution by Clinical Pharmacists in a Family Medicine Residency Clinic.

PURPOSE: There are limited data to evaluate the impact of ambulatory clinical pharmacist recommendations on family medicine resident prescribing and monitoring of medications. The purpose of this study is to begin to gain insight in this area by answering the research question, "How many ambulatory clinical pharmacist recommendations for drug therapy problem (DTP) resolution are implemented on the day of a medication therapy management (MTM) visit in an outpatient family medicine residency clinic?" METHODS: This is a retrospective chart review of face-to-face MTM encounters conducted by ambulatory clinical pharmacists (including pharmacist residents) from August 1, 2012 to June 30, 2015 at a family medicine residency clinic. Descriptive statistics were conducted to both quantify the number of DTPs identified and resolved on the day of the MTM visit as well as categorize the DTPs. RESULTS: Based on the 728 MTM encounters analyzed, patients were an average of 53.6 years old and took 11.9 medications to treat 5.7 medical conditions. A total of 3057 DTPs were identified in the 728 encounters, of which 1303 were resolved the same day as the MTM visit. This resulted in an average of 4.2 DTPs identified and 2.0 resolved per visit per patient. The most common DTP category identified in this study was the need for additional drug therapy (41.6%). CONCLUSIONS: Approximately half of the ambulatory clinical pharmacist's DTP resolution recommendations were implemented the same day they were identified, which highlights the strength of team-based patient care and interprofessional collaboration in a residency teaching clinic.

Progestin-primed ovarian stimulation with or without clomiphene citrate supplementation in normal ovulatory women undergoing in vitro fertilization/intracytoplasmic sperm injection: A prospective randomized controlled trial.

OBJECTIVE: To compare the endocrinological profiles, cycle characteristics and pregnancy outcomes of progestin-primed ovarian stimulation (PPOS) with or without clomiphene citrate (CC) supplementation in normal ovulatory women undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). DESIGN: Prospective randomized controlled study. PATIENT(S): A total of 320 infertile women undergoing IVF/ICSI. Medroxyprogesterone acetate (MPA) and human menopausal gonadotropin (hMG) were simultaneously administered on menstrual cycle day 3. The women were randomized into 2 equal groups with or without CC supplementation. MEASURES: The primary outcome measure was the percentage of women with profound pituitary suppression (luteinizing hormone [LH] <1.0 IU/L on the trigger day). The secondary outcomes were endocrinological profiles, cycle characteristics and pregnancy outcomes. RESULTS: The percentage of women with profound pituitary suppression was significantly lower in the study group (hMG + MPA + CC) than in the control group (hMG + MPA) (1.9% vs 33.1%, P < .001). The mean LH level during controlled ovarian stimulation (COS) was higher in the study group than in the control group (P < .001), but none of the patients in either group exhibited a premature LH surge. The doses of Gn in the study group were significantly lower than those in the control group (1334.06 ± 212.53 IU vs 1488.28 ± 325.08 IU, P < .001). The number of oocytes retrieved was similar between the 2 groups (10.03 ± 5.97 vs 10.34 ± 7.52, P > .05). No significant differences were observed in either the number of viable embryos or the pregnancy outcomes between the 2 groups. CONCLUSION(S): Clomiphene citrate is an effective adjuvant to alleviate pituitary suppression in the PPOS protocol; however, it has no impact on clinical outcomes.

Cell Fate Decision as High-Dimensional Critical State Transition.

Cell fate choice and commitment of multipotent progenitor cells to a differentiated lineage requires broad changes of their gene expression profile. But how progenitor cells overcome the stability of their gene expression configuration (attractor) to exit the attractor in one direction remains elusive. Here we show that commitment of blood progenitor cells to the erythroid or myeloid lineage is preceded by the destabilization of their high-dimensional attractor state, such that differentiating cells undergo a critical state transition. Single-cell resolution analysis of gene expression in populations of differentiating cells affords a new quantitative index for predicting critical transitions in a high-dimensional state space based on decrease of correlation between cells and concomitant increase of correlation between genes as cells approach a tipping point. The detection of "rebellious cells" that enter the fate opposite to the one intended corroborates the model of preceding destabilization of a progenitor attractor. Thus, early warning signals associated with critical transitions can be detected in statistical ensembles of high-dimensional systems, offering a formal theory-based approach for analyzing single-cell molecular profiles that goes beyond current computational pattern recognition, does not require knowledge of specific pathways, and could be used to predict impending major shifts in development and disease.

Ursolic acid inhibits proliferation and reverses drug resistance of ovarian cancer stem cells by downregulating ABCG2 through suppressing the expression of hypoxia-inducible factor-1α in vitro.

Hypoxia in tumors is closely related to drug resistance. It has not been verified whether hypoxia-inducible factor-1α (HIF-1α) or ABCG2 is related to hypoxia-induced resistance. Ursolic acid (UA), when used in combination with cisplatin can significantly increase the sensitivity of ovarian cancer stem cells (CSCs) to cisplatin, but the exact mechanism is unknown. The cell growth inhibitory rate of cisplatin under different conditions was evaluated using Cell Counting Kit-8 (CCK-8) in adherence and sphere cells (SKOV3, A2780, and HEY). The expression of HIF-1α and ABCG2 was tested using quantitative PCR, western blotting, and immuno-fluorescence under different culture conditions and treated with UA. Knockdown of HIF-1α by shRNA and LY294002 was used to inhibit the activity of PI3K/Akt pathway. Ovarian CSCs express stemness-related genes and drug resistance significantly higher than normal adherent cells. Under hypoxic conditions, the ovarian CSCs grew faster and were more drug resistant than under normoxia. UA could inhibit proliferation and reverse the drug resistance of ovarian CSC by suppressing ABCG2 and HIF-1α under different culture conditions. HIF-1α inhibitor YC-1 combined with UA suppressed the stemness genes and ABCG2 under hypoxic condition. The PI3K/Akt signaling pathway activation plays an important functional role in UA-induced downregulation of HIF-1α and reduction of ABCG2. UA inhibits the proliferation and reversal of drug resistance in ovarian CSCs by suppressing the expression of downregulation of HIF-1α and ABCG2.

Entropy, Ergodicity, and Stem Cell Multipotency.

Populations of mammalian stem cells commonly exhibit considerable cell-cell variability. However, the functional role of this diversity is unclear. Here, we analyze expression fluctuations of the stem cell surface marker Sca1 in mouse hematopoietic progenitor cells using a simple stochastic model and find that the observed dynamics naturally lie close to a critical state, thereby producing a diverse population that is able to respond rapidly to environmental changes. We propose an information-theoretic interpretation of these results that views cellular multipotency as an instance of maximum entropy statistical inference.

Preventing preterm births: analysis of trends and potential reductions with interventions in 39 countries with very high human development index.

BACKGROUND: Every year, 1·1 million babies die from prematurity, and many survivors are disabled. Worldwide, 15 million babies are born preterm (<37 weeks' gestation), with two decades of increasing rates in almost all countries with reliable data. The understanding of drivers and potential benefit of preventive interventions for preterm births is poor. We examined trends and estimate the potential reduction in preterm births for countries with very high human development index (VHHDI) if present evidence-based interventions were widely implemented. This analysis is to inform a rate reduction target for Born Too Soon. METHODS: Countries were assessed for inclusion based on availability and quality of preterm prevalence data (2000-10), and trend analyses with projections undertaken. We analysed drivers of rate increases in the USA, 1989-2004. For 39 countries with VHHDI with more than 10,000 births, we did country-by-country analyses based on target population, incremental coverage increase, and intervention efficacy. We estimated cost savings on the basis of reported costs for preterm care in the USA adjusted using World Bank purchasing power parity. FINDINGS: From 2010, even if all countries with VHHDI achieved annual preterm birth rate reductions of the best performers for 1990-2010 (Estonia and Croatia), 2000-10 (Sweden and Netherlands), or 2005-10 (Lithuania, Estonia), rates would experience a relative reduction of less than 5% by 2015 on average across the 39 countries. Our analysis of preterm birth rise 1989-2004 in USA suggests half the change is unexplained, but important drivers include non-medically indicated labour induction and caesarean delivery and assisted reproductive technologies. For all 39 countries with VHHDI, five interventions modelling at high coverage predicted a 5% relative reduction of preterm birth rate from 9·59% to 9·07% of livebirths: smoking cessation (0·01 rate reduction), decreasing multiple embryo transfers during assisted reproductive technologies (0·06), cervical cerclage (0·15), progesterone supplementation (0·01), and reduction of non-medically indicated labour induction or caesarean delivery (0·29). These findings translate to roughly 58,000 preterm births averted and total annual economic cost savings of about US$3 billion. INTERPRETATION: We recommend a conservative target of a relative reduction in preterm birth rates of 5% by 2015. Our findings highlight the urgent need for research into underlying mechanisms of preterm births, and development of innovative interventions. Furthermore, the highest preterm birth rates occur in low-income settings where the causes of prematurity might differ and have simpler solutions such as birth spacing and treatment of infections in pregnancy than in high-income countries. Urgent focus on these settings is also crucial to reduce preterm births worldwide. FUNDING: March of Dimes, USA, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and National Institutes of Health, USA.

ObesiTV: how television is influencing the obesity epidemic.

Obesity is a major public health concern in the United States. Over the last several decades, the prevalence of obesity among both adults and children has grown at an alarming rate and is now reaching epidemic proportions. The increase in obesity has been associated with rises in a host of other chronic conditions including cardiovascular disease, type 2 diabetes, and some cancers. While the causes of obesity are multifaceted, there is growing evidence that television viewing is a major contributor. Results of numerous studies indicate a direct association between time spent watching television and body weight. Possible explanations for this relationship include: 1) watching television acts as a sedentary replacement for physical activity; 2) food advertisements for nutrient-poor, high-calorie foods stimulate food intake; and 3) television viewing is associated with "mindless" eating. In addition to decreasing physical activity and increasing the consumption of highly palatable foods, television viewing can also promote weight gain in indirect ways, such as through the use of targeted product placements in television shows; by influencing social perceptions of body image; and airing programs that portray cooking, eating and losing weight as entertainment. This paper will provide an interdisciplinary review of the direct and indirect ways in which television influences the obesity epidemic, and conclude with ways in which the negative impact of television on obesity could be reduced.

Parametric modeling of cellular state transitions as measured with flow cytometry.

BACKGROUND: Gradual or sudden transitions among different states as exhibited by cell populations in a biological sample under particular conditions or stimuli can be detected and profiled by flow cytometric time course data. Often such temporal profiles contain features due to transient states that present unique modeling challenges. These could range from asymmetric non-Gaussian distributions to outliers and tail subpopulations, which need to be modeled with precision and rigor. RESULTS: To ensure precision and rigor, we propose a parametric modeling framework StateProfiler based on finite mixtures of skew t-Normal distributions that are robust against non-Gaussian features caused by asymmetry and outliers in data. Further, we present in StateProfiler a new greedy EM algorithm for fast and optimal model selection. The parsimonious approach of our greedy algorithm allows us to detect the genuine dynamic variation in the key features as and when they appear in time course data. We also present a procedure to construct a well-fitted profile by merging any redundant model components in a way that minimizes change in entropy of the resulting model. This allows precise profiling of unusually shaped distributions and less well-separated features that may appear due to cellular heterogeneity even within clonal populations. CONCLUSIONS: By modeling flow cytometric data measured over time course and marker space with StateProfiler, specific parametric characteristics of cellular states can be identified. The parameters are then tested statistically for learning global and local patterns of spatio-temporal change. We applied StateProfiler to identify the temporal features of yeast cell cycle progression based on knockout of S-phase triggering cyclins Clb5 and Clb6, and then compared the S-phase delay phenotypes due to differential regulation of the two cyclins. We also used StateProfiler to construct the temporal profile of clonal divergence underlying lineage selection in mammalian hematopoietic progenitor cells.