Do Postoperative Surgeon Phone Calls Improve Outcomes Following Mandibular Fracture Repair?

BACKGROUND: Complications of open reduction and internal fixation (ORIF) of mandibular fractures are influenced by several patient factors. A postoperative surgeon phone call could modify these factors through education and reinforcement of instructions, but its effect has not been studied. PURPOSE: The purpose of this study was to measure and compare the frequencies of postoperative inflammatory complications (POICs) following ORIF of mandibular fractures in patients who did and did not receive a postoperative surgeon phone call. STUDY DESIGN, SETTING, SAMPLE: The authors conducted an ambispective cohort study consisting of patients with mandibular fractures treated with ORIF at a large urban trauma hospital with the prospective cohort from January 1, 2021 to March 31, 2022 and a retrospective cohort from April 1, 2020 to December 31, 2020. Prisoners and patients with gunshot wounds were excluded. PREDICTOR VARIABLE: The primary predictor variable was the surgeon call group. After January 2021, a postoperative call was implemented 1-3 days following fracture repair to review instructions, such as nonchew diet and oral hygiene, and provide education, such as reviewing expectations. Prior to January 2021, patients were not called. This resulted in 3 categories: Not Called, Called and Answered, and No Answer. MAIN OUTCOME VARIABLES: The primary outcome variable was POICs, defined as the occurrence of exposed or infected hardware, abscess formation, recurrent swelling/pain, nonunion, osteomyelitis, or fistula formation. COVARIATES: Demographic variables, injury-related variables, and treatment-related variables were also measured. ANALYSES: Statistical analysis was performed using Fisher's exact and Wilcoxon rank-sum tests, as well as multivariable logistic regression. A P value was considered significant if < .05. RESULTS: Of the 178 patients in the study, 137 (77%) were male and the average age was 39.9 ± 12.6 years. Sixty-five patients (36.5%) were not called. Of the patients called, 79 (44.4%) answered and 34 (19.1%) did not answer. POICs occurred in 9.2% of the Not Called group and 8.9% of the Called and Answered group (P = .99). In the No Answer group, 29.4% had POICs, which was higher than the other 2 groups (P = .01). CONCLUSION AND RELEVANCE: A surgeon phone call was not associated with complication rates; however, patients in the No Answer group were significantly more likely to experience a POIC.

Poor nutrition status associated with low patient satisfaction six months into treatment for head and neck/esophageal cancer treatment: A prospective multicenter cohort study.

BACKGROUND: Patient-reported outcome measures have been associated with survival in oncology patients. Altered intake and malnutrition are common symptoms for patients treated for head and neck cancer and esophageal cancer (HNC/EC). The purpose of this study was to examine the relationship between patient-reported satisfaction with medical care and nutrition status. METHODS: This prospective cohort study collected data from 11 international cancer care sites. RESULTS: One hundred and sixtythree adult patients (n = 115 HNC; n = 48 EC) completed a patient satisfaction questionnaire (the Canadian Health Care Evaluation Project Lite) and were included. HNC/EC patient global satisfaction with medical care was 88.3/100 ± 15.3 at baseline and remained high at 86.6/100 ± 16.8 by 6 months (100 max satisfaction score). Poor nutrition status, as defined by the Patient-Generated Subjective Global Assessment Short Form, was associated with lower patient satisfaction with overall medical care, relationship with doctors, illness management, communication, and decision-making 6 months into treatment (P < 0.01). There was no difference in global satisfaction between patients who did and did not report swallowing difficulty (P = 0.99) and patients with and without feeding tube placement (P = 0.36). Patients who were seen by a dietitian for at least one nutrition assessment had global satisfaction with care that was 16.7 percentage points higher than those with no nutrition assessment (89.3 ± 13.8 vs 72.6 ± 23.6; P = 0.005) CONCLUSION: In HNC/EC patient-centered oncology care, decreasing malnutrition risk and providing access to dietitian-led nutrition assessments should be prioritized and supported to improve patient satisfaction and standard of care. Feeding tube placement did not decrease patient satisfaction with medical care.

Final, 10-Year Outcomes with Nivolumab plus Ipilimumab in Advanced Melanoma.

BACKGROUND: Previous results from this trial showed longer overall survival after treatment with nivolumab plus ipilimumab or with nivolumab monotherapy than with ipilimumab monotherapy in patients with advanced melanoma. Given that patients with advanced melanoma are living longer than 7.5 years, longer-term data were needed to address new clinically relevant questions. METHODS: We randomly assigned patients with previously untreated advanced melanoma, in a 1:1:1 ratio, to one of the following regimens: nivolumab (1 mg per kilogram of body weight) plus ipilimumab (3 mg per kilogram) every 3 weeks for four doses, followed by nivolumab (3 mg per kilogram) every 2 weeks; nivolumab (3 mg per kilogram) every 2 weeks plus placebo; or ipilimumab (3 mg per kilogram) every 3 weeks for four doses plus placebo. Treatment was continued until the occurrence of disease progression, unacceptable toxic effects, or withdrawal of consent. Randomization was stratified according to BRAF mutation status, metastasis stage, and programmed death ligand 1 expression. Here, we report the final, 10-year results of this trial, including results for overall survival and melanoma-specific survival, as well as durability of response. RESULTS: With a minimum follow-up of 10 years, median overall survival was 71.9 months with nivolumab plus ipilimumab, 36.9 months with nivolumab, and 19.9 months with ipilimumab. The hazard ratio for death was 0.53 (95% confidence interval [CI], 0.44 to 0.65) for nivolumab plus ipilimumab as compared with ipilimumab and was 0.63 (95% CI, 0.52 to 0.76) for nivolumab as compared with ipilimumab. Median melanoma-specific survival was more than 120 months with nivolumab plus ipilimumab (not reached, with 37% of the patients alive at the end of the trial), 49.4 months with nivolumab, and 21.9 months with ipilimumab. Among patients who had been alive and progression-free at 3 years, 10-year melanoma-specific survival was 96% with nivolumab plus ipilimumab, 97% with nivolumab, and 88% with ipilimumab. CONCLUSIONS: The final trial results showed a continued, ongoing survival benefit with nivolumab plus ipilimumab and with nivolumab monotherapy, as compared with ipilimumab monotherapy, in patients with advanced melanoma. (Funded by Bristol Myers Squibb and others; CheckMate 067 ClinicalTrials.gov number, NCT01844505.).

Beyond KRAS(G12C): Biochemical and Computational Characterization of Sotorasib and Adagrasib Binding Specificity and the Critical Role of H95 and Y96.

Mutated KRAS proteins are frequently expressed in some of the most lethal human cancers and thus have been a target of intensive drug discovery efforts for decades. Lately, KRAS(G12C) switch-II pocket (SII-P)-targeting covalent small molecule inhibitors have finally reached clinical practice. Sotorasib (AMG-510) was the first FDA-approved covalent inhibitor to treat KRAS(G12C)-positive nonsmall cell lung cancer (NSCLC), followed soon by adagrasib (MRTX849). Both drugs target the GDP-bound state of KRAS(G12C), exploiting the strong nucleophilicity of acquired cysteine. Here, we evaluate the similarities and differences between sotorasib and adagrasib in their RAS SII-P binding by applying biochemical, cellular, and computational methods. Exact knowledge of SII-P engagement can enable targeting this site by reversible inhibitors for KRAS mutants beyond G12C. We show that adagrasib is strictly KRAS- but not KRAS(G12C)-specific due to its strong and unreplaceable interaction with H95. Unlike adagrasib, sotorasib is less dependent on H95 for its binding, making it a RAS isoform-agnostic compound, having a similar functionality also with NRAS and HRAS G12C mutants. Our results emphasize the accessibility of SII-P beyond oncogenic G12C and aid in understanding the molecular mechanism behind the clinically observed drug resistance, associated especially with secondary mutations on KRAS H95 and Y96.

Long-term engrafting multilineage hematopoietic cells differentiated from human induced pluripotent stem cells.

Hematopoietic stem cells (HSCs) derived from human induced pluripotent stem cells (iPS cells) have important biomedical applications. We identified differentiation conditions that generate HSCs defined by robust long-term multilineage engraftment in immune-deficient NOD,B6.Prkdcscid Il2rgtm1Wjl/SzJ KitW41/W41 mice. We guided differentiating iPS cells, as embryoid bodies in a defined culture medium supplemented with retinyl acetate, through HOXA-patterned mesoderm to hemogenic endothelium specified by bone morphogenetic protein 4 and vascular endothelial growth factor (VEGF). Removal of VEGF facilitated an efficient endothelial-to-hematopoietic transition, evidenced by release into the culture medium of CD34+ blood cells, which were cryopreserved. Intravenous transplantation of two million thawed CD34+ cells differentiated from four independent iPS cell lines produced multilineage bone marrow engraftment in 25-50% of immune-deficient recipient mice. These functionally defined, multipotent CD34+ hematopoietic cells, designated iPS cell-derived HSCs (iHSCs), produced levels of engraftment similar to those achieved following umbilical cord blood transplantation. Our study provides a step toward the goal of generating HSCs for clinical translation.

Rare Right-Sided Posterolateral Diaphragmatic Hernia in an Adult Presenting as an Incarcerated Large Bowel Obstruction: A Case Report.

Introduction: A diaphragmatic hernia (DH) is a defect within a part of the diaphragm that allows intra-abdominal contents to enter the thoracic cavity. Diaphragmatic hernias can be congenital or acquired later in life. The most common congenital DH is the Bochdalek hernia (posterolateral hernia), but the most commonly acquired DH is due to traumatic injury. These hernias are rare in adults and are typically diagnosed incidentally. Surgical repair is the standard of care; however, data regarding the surgical approach is scarce. We report a case of a rare right posterolateral DH in an adult female patient who presented with acute abdominal pain. Case Presentation: A 69-year-old female presented with recurrent epigastric pain that had acutely worsened, nausea, vomiting, and food intolerance. A computed tomography (CT) scan demonstrated a right posterolateral DH containing the hepatic flexure of the colon. The patient was taken urgently to surgery due to concern for strangulation. Reduction of the hernia was attempted laparoscopically but was converted to an open procedure with a subcostal incision due to poor visualization. This approach revealed adequate exposure of the defect and subsequent reduction of the herniated abdominal contents. The defect was easily closed without tension or the use of mesh. The patient was discharged on postoperative day 3. Conclusion: Chronic DH can have severe life-threatening sequelae when left untreated. This case demonstrates the importance of thorough history-taking and raises awareness of missed diaphragmatic injuries in trauma situations. Since patients who present with a symptomatic DH often need urgent repair, it is important for surgeons working in the acute care setting to understand the surgical options available and when mesh placement may benefit the situation. Our case outlines a successful primary defect repair, without mesh, of a right-sided DH in which a minimally invasive technique was attempted but converted to laparotomy for patient safety.

Conformationally Constrained Isoquinolinones as Orally Efficacious Hepatitis B Capsid Assembly Modulators.

Isoquinolinone-based HBV capsid assembly modulators that bind at the dimer:dimer interface of HBV core protein have been shown to suppress viral replication in chronic hepatitis B patients. Analysis of their binding mode by protein X-ray crystallography has identified a region of the small molecule where the application of a constraint can lock the preferred binding conformation and has allowed for further optimization of this class of compounds. Key analogues demonstrated single digit nM EC50 values in reducing HBV DNA in a HepDE19 cellular assay in addition to favorable ADME and pharmacokinetic properties, leading to a high degree of oral efficacy in a relevant in vivo hydrodynamic injection mouse model of HBV infection, with 12e effecting a 3 log10 decline in serum HBV DNA levels at a once daily dose of 1 mg/kg. Additionally, maintenance of activity was observed in clinically relevant HBV core protein variants T33N and I105T.

Integrated epigenomic exposure signature discovery.

Aim: The epigenome influences gene regulation and phenotypes in response to exposures. Epigenome assessment can determine exposure history aiding in diagnosis.Materials & methods: Here we developed and implemented a machine learning algorithm, the exposure signature discovery algorithm (ESDA), to identify the most important features present in multiple epigenomic and transcriptomic datasets to produce an integrated exposure signature (ES).Results: Signatures were developed for seven exposures including Staphylococcus aureus, human immunodeficiency virus, SARS-CoV-2, influenza A (H3N2) virus and Bacillus anthracis vaccinations. ESs differed in the assays and features selected and predictive value.Conclusion: Integrated ESs can potentially be utilized for diagnosis or forensic attribution. The ESDA identifies the most distinguishing features enabling diagnostic panel development for future precision health deployment.

This article introduces ESDA, a new analytic tool for integrating multiple data types to identify the most distinguishing features following an exposure. Using the ESDA, we were able to identify signatures of infectious diseases. The results of the study indicate that integration of multiple types of large datasets can be used to identify distinguishing features for infectious diseases. Understanding the changes from different exposures will enable development of diagnostic tests for infectious diseases that target responses from the patient. Using the ESDA, we will be able to build a database of human response signatures to different infections and simplify diagnostic testing in the future.

Frailty and Long-Term Mortality Following Emergency Laparotomy: A Comparison Between the 11-Item and 5-Item Modified Frailty Indices.

INTRODUCTION: Emergency laparotomy (EL) is a high-risk operation which is increasingly performed on an aging patient population. Objective frailty assessment using a validated index has the potential to improve preoperative risk stratification. This study aimed to assess the correlation between frailty and long-term mortality and morbidity outcomes for older EL patients. Secondary aims were to compare the 11-item and shortened five-item modified frailty indices (mFIs) in terms of value and predictive validity. METHODS: A prospective multicenter observational study of patients aged ≥55 y undergoing EL was conducted across five hospitals in New Zealand between 2017 and 2022. Frailty was measured using the 11-item and abbreviated five-item mFIs. Multivariable logistic regression was used to determine whether frailty was independently associated with one-year postoperative mortality and other morbidity outcomes. Correlation between the two frailty indices were assessed with the Spearman's correlation coefficient (P). RESULTS: Frailty assessments were performed in 861 participants, with the prevalence being 18.7% and 29.8% using the 11-item and five-item mFIs, respectively. Both frailty indices demonstrated similar associations with one-year mortality (two-fold increased risk), major complications, admission to intensive care unit, rehabilitation, and 30-d readmission. The 11-item mFI demonstrated a greater association with early mortality (four-fold increased risk), reoperations, and increased length of stay compared with the five-item frailty index. Spearman P was 0.6 (P < 0.001). CONCLUSIONS: Frailty, as identified by the 11-item and five-item mFIs, was associated with one-year mortality and other important morbidity outcomes for older EL patients. These forms of frailty assessment provide important information that may aid in risk assessment and patient-centered decision-making.

Personalised penetrance estimation for C9orf72-related amyotrophic lateral sclerosis and frontotemporal dementia.

Background: C9orf72 hexanucleotide repeat expansions are the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) in European populations. Variable disease penetrance between families presents a challenge for genetic counselling of at-risk relatives and reduces the predictive utility of testing asymptomatic relatives. We have developed a novel model for estimating penetrance in individual families affected by C9orf72 using available family history information, allowing the calculation of personalised risk estimates. Methods: Published aggregated age-of-onset data for C9orf72-related ALS/FTD were used to generate age-related cumulative relative risks for at-risk relatives within pedigrees. Age-related relative risks are combined with a priori chance of individuals carrying an expansion based on known pedigree information. Penetrance is calculated as a number of affected individuals divided by the sum of cumulative age-related risks of relatives being affected by 80 years. Results: This method allows family-specific penetrance to be estimated from family history and at-risk relatives' personalised age-related ALS/FTD risks to be calculated and illustrated graphically. Penetrance reduces as the number and age of at-risk unaffected relatives increases. Conclusions: Family history remains the best indicator of penetrance in C9orf72 expansion carriers. Calculating family-specific penetrance can aid genetic counselling by allowing at-risk relatives a more accurate understanding of their individual risk.

Prevalence and macrolide resistance of Mycoplasma genitalium from patients seeking sexual health care in Southern Ghana.

BACKGROUND: Mycoplasma genitalium (MG), a sexually transmitted infection (STI), has emerged as a common cause of non-gonococcal urethritis and cervicitis worldwide, with documented resistance to commonly used antibiotics including doxycycline and azithromycin. Data in Ghana regarding the prevalence of MG is limited. METHODS: This retrospective study investigated MG presence and macrolide resistance among patients who previously reported to selected clinics for STI symptoms between December 2012 and June 2020. Samples were screened for MG and mutations associated with azithromycin resistance were investigated using Nucleic Acid Amplification Testing (NAAT) including the Resistance Plus MG® kit from SpeeDx and the LightMix® kit for MG, combined with the Modular Mycoplasma Macrolide from TIB Molbiol. RESULTS: A total of 1,015 samples were screened, out of which MG infection rate by TIB Molbiol and SpeeDx were 3.1% and 3.4%, respectively. The mutation responsible for macrolide resistance was detected in one MG positive sample by both assays. Both diagnostic tests revealed no significant association between MG infection and socio-demographic characteristics, clinical symptoms, gonorrhea, and chlamydia infection status. There was no significant difference in the mycoplasma percentage positivity rate detected using SpeeDx (3.4%) and TIB Molbiol (3.1%). CONCLUSIONS: While not commonly tested as a cause of STI symptoms, MG is widespread in Ghana, exhibiting symptoms and prevalence comparable to those in other countries and linked to antimicrobial resistance. Future research using various molecular techniques is essential to monitor resistance trends and guide future antibiotic choices.

How appraisals of an in-group's collective history shape collective identity and action: Evidence in relation to African identity.

This research tested the impact of how group members appraise their collective history on in-group identification and group-based action in the African context. Across three experiments (Ns = 950; 270; and 259) with Nigerian participants, we tested whether the effect of historical representations-specifically the valence of the in-group's collective history-on in-group engagement, in turn, depends on whether that history is also appraised as subjectively important. In Study 1, findings from exploratory moderated-mediation analyses indicated that the appraised negative valence of African history was associated with an increase in identification and group-based action when African history was appraised as unimportant (history-as-contrast). Conversely, the appraised positive valence of African history was also associated with an increase in identification and group-based action when African history was also appraised as important (history-as-inspiration). Studies 2a and 2b then orthogonally manipulated the valence and subjective importance of African history. However, findings from Studies 2a and 2b did not replicate those of Study 1. Altogether, our findings suggest that the relationship between historical representations of groups and in-group identification and group-based action in the present is more complex than previously acknowledged.

Physicochemical Properties, Functionalities, and Antioxidant Activity of Protein Extracts from New Zealand Wild Sea Cucumbers (Australostichopus mollis).

This study investigated the physicochemical properties, functionalities, and antioxidant capacities of protein extracts from wild sea cucumber Australostichopus mollis collected from four distinct locations in New Zealand. Protein was extracted from sea cucumber body walls using trypsin enzymatic extraction, followed by cold acetone precipitation. The amino acid analysis revealed high glycine (189.08 mg/g), glutamic acid (119.45 mg/g), and aspartic acid (91.91 mg/g) concentrations in all samples. The essential amino acid indexes of the protein extracts (62.96, average) were higher than the WHO/FAO standard references, indicating the excellent protein quality of A. mollis. Furthermore, protein extracts from A. mollis demonstrated superior emulsifying activity (202.3-349.5 m2/g average) compared to commercial soy and whey protein isolates under all tested pH conditions, and enhanced foaming capacity (109.9-126.4%) and stability (52.7-72%) in neutral and acidic conditions. The extracts also exhibited good solubility, exceeding 70% across pH 3-11. Antioxidant capacities (ABTS and DPPH free radical scavenging activity and ferric reducing antioxidant power) were identified in A. mollis protein extracts for the first time, with clear variations observed among different locations. These findings elucidate the advantageous functional properties of protein extracts from wild New Zealand A. mollis and highlight their potential application as high-quality antioxidant food ingredients.

Maternal ketone supplementation throughout gestation improves neonatal cardiac dysfunction caused by perinatal iron deficiency.

Iron deficiency (ID) is common during gestation and in early infancy and has been shown to adversely affect cardiac development and function, which could lead to lasting cardiovascular consequences. Ketone supplementation has been shown to confer cardioprotective effects in numerous disease models. Here, we tested the hypothesis that maternal ketone supplementation during gestation would mitigate cardiac dysfunction in ID neonates. Female Sprague-Dawley rats were fed an iron-restricted or iron-replete diet before and throughout pregnancy. Throughout gestation, iron-restricted dams were given either a daily subcutaneous injection of ketone solution (containing ß-hydroxybutyrate [ßOHB]) or saline (vehicle). Neonatal offspring cardiac function was assessed by echocardiography at postnatal days (PD)3 and 13. Hearts and livers were collected post-mortem for assessments of mitochondrial function and gene expression profiles of markers oxidative stress and inflammation. Maternal iron restriction caused neonatal anemia and asymmetric growth restriction at all time points assessed, and maternal ßOHB treatment had no effect on these outcomes. Echocardiography revealed reduced ejection fraction despite enlarged hearts (relative to body weight) in ID offspring, resulting in impaired oxygen delivery, which was attenuated by maternal ßOHB supplementation. Further, maternal ketone supplementation affected biochemical markers of mitochondrial function, oxidative stress and inflammation in hearts of neonates, implicating these pathways in the protective effects conferred by ßOHB. In summary, ßOHB supplementation confers protection against cardiac dysfunction in ID neonates and could have implications for the treatment of anemic babies.

Rational Design, Synthesis, and Structure-Activity Relationship of a Novel Isoquinolinone-Based Series of HBV Capsid Assembly Modulators Leading to the Identification of Clinical Candidate AB-836.

Inhibition of Hepatitis B Virus (HBV) replication by small molecules that modulate capsid assembly and the encapsidation of pgRNA and viral polymerase by HBV core protein is a clinically validated approach toward the development of new antivirals. Through definition of a minimal pharmacophore, a series of isoquinolinone-based capsid assembly modulators (CAMs) was identified. Structural biology analysis revealed that lead molecules possess a unique binding mode, exploiting electrostatic interactions with accessible phenylalanine and tyrosine residues. Key analogs demonstrated excellent primary potency, absorption, distribution, metabolism, and excretion (ADME) and pharmacokinetic properties, and efficacy in a mouse model of HBV. The optimized lead also displayed potent inhibition of capsid uncoating in HBV-infected HepG2 cells expressing the sodium-taurocholate cotransporting polypeptide (NTCP) receptor, affecting the generation of HBsAg and cccDNA establishment. Based on these results, isoquinolinone derivative AB-836 was advanced into clinical development. In Phase 1b trials, AB-836 demonstrated >3 log10 reduction in serum HBV DNA, however, further development was discontinued due to the observation of incidental alanine aminotransferase (ALT) elevations.

Genomic analysis defines distinct pancreatic and neuronal subtypes of lung carcinoid.

Lung carcinoids (L-CDs) are rare, poorly characterised neuroendocrine tumours (NETs). L-CDs are more common in women and are not the consequence of cigarette smoking. They are classified histologically as typical carcinoids (TCs) or atypical carcinoids (ACs). ACs confer a worse survival. Histological classification is imperfect, and there is increasing interest in molecular markers. We therefore investigated global transcriptomic and epigenomic profiles of 15 L-CDs resected with curative intent at Royal Brompton Hospital. We identified underlying mutations and structural abnormalities through whole-exome sequencing (WES) and single nucleotide polymorphism (SNP) genotyping. Transcriptomic clustering algorithms identified two distinct L-CD subtypes. These showed similarities either to pancreatic or neuroendocrine tumours at other sites and so were named respectively L-CD-PanC and L-CD-NeU. L-CD-PanC tumours featured upregulation of pancreatic and metabolic pathway genes matched by promoter hypomethylation of genes for beta cells and insulin secretion (p < 1 × 10-6). These tumours were centrally located and showed mutational signatures of activation-induced deaminase/apolipoprotein B editing complex  activity, together with genome-wide DNA methylation loss enriched in repetitive elements (p = 2.2 × 10-16). By contrast, the L-CD-NeU group exhibited upregulation of neuronal markers (adjusted p < 0.01) and was characterised by focal spindle cell morphology (p = 0.04), peripheral location (p = 0.01), high mutational load (p = 2.17 × 10-4), recurrent copy number alterations, and enrichment for ACs. Mutations affected chromatin remodelling and SWI/SNF complex pathways. L-CD-NeU tumours carried a mutational signature attributable to aflatoxin and aristolochic acid (p = 0.05), suggesting a possible environmental exposure in their pathogenesis. Immunologically, myeloid and T-cell markers were enriched in L-CD-PanC and B-cell markers in L-CD-NeU tumours. The substantial epigenetic and non-coding differences between L-CD-PanC and L-CD-NeU open new possibilities for biomarker selection and targeted treatment of L-CD. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

The exchange dynamics of biomolecular condensates.

A hallmark of biomolecular condensates formed via liquid-liquid phase separation is that they dynamically exchange material with their surroundings, and this process can be crucial to condensate function. Intuitively, the rate of exchange can be limited by the flux from the dilute phase or by the mixing speed in the dense phase. Surprisingly, a recent experiment suggests that exchange can also be limited by the dynamics at the droplet interface, implying the existence of an 'interface resistance'. Here, we first derive an analytical expression for the timescale of condensate material exchange, which clearly conveys the physical factors controlling exchange dynamics. We then utilize sticker-spacer polymer models to show that interface resistance can arise when incident molecules transiently touch the interface without entering the dense phase, i.e., the molecules 'bounce' from the interface. Our work provides insight into condensate exchange dynamics, with implications for both natural and synthetic systems.

Pulsed Laser Deposition of Epitaxial SrTiO3/Sr3Al2O6 Templates as a Water-Soluble Sacrificial Layer for GaAs Growth and Lift-Off.

Despite the record-high efficiency of GaAs solar cells, their terrestrial application is limited due to both the particularly high costs related to the required single-crystal substrates and epitaxial growth. A water-soluble lift-off layer could reduce costs by avoiding the need for toxic and dangerous etchants, substrate repolishing, and expensive process steps. Sr3Al2O6 (SAO) is a water-soluble cubic oxide, and SrTiO3 (STO) is a perovskite oxide, where a SAO ≈ 4 × a STO ≈ (2√2)a GaAs. Here, the pulsed laser-deposited epitaxial growth of SrTiO3/Sr3Al2O6 templates on STO and Ge substrates for epitaxial GaAs growth was investigated, where SAO works as a sacrificial layer and STO protects the hygroscopic SAO during substrate transfer between deposition chambers. We identified that the SAO film quality is strongly dependent on the growth temperature and the O2 partial pressure, where either a high T or a high P(O2) improves the quality. XRD spectra of the films with optimized deposition parameters showed an epitaxial STO/SAO stack aligned to the STO (100) substrate, and TEM analysis revealed that the grown films were epitaxially crystalline throughout the thickness. The STO/SAO growth on Ge substrates at a high T with no intentional O2 flow resulted in some nonepitaxial grains and surface pits, likely due to partial Ge oxidation. GaAs was grown by metalorganic vapor-phase epitaxy (MOVPE) on STO/SAO/STO templates. Lift-off after dissolving the sacrificial SAO in water resulted in free-standing ⟨001⟩ preferentially oriented polycrystalline GaAs.

Effectiveness of a Novel Feeding Algorithm for Oral Feeding Transition of Infants Born Prematurely.

BACKGROUND: Feeding skill acquisition is commonly a limiting factor determining when an infant born prematurely can be discharged. PURPOSE: This study aimed to determine if the addition of a novel feeding progression algorithm (combination of objective data from a suck measurement device and slow flow/low variability nipples) to current neonatal intensive care unit (NICU) standards could decrease feeding-related length of stay (primary outcome). We hypothesized that by timing the initiation of oral feedings to coincide with adequate sensory-motor skill development, feeding-related length of stay may be decreased. METHODS: This was a prospective intervention study, with a historical control cohort, of infants born less than 30 weeks' gestational age without comorbidities affecting feeding skill acquisition at a Regional Level III-S NICU at a women and infant's hospital in Louisiana. A novel feeding progression algorithm utilized objective assessment of sucking to determine progression in nipple flow rates with slow flow/low variability nipples (flow rates from 0 to 9 mL/min) for infants receiving intervention (n = 18). Thirty-six controls who did not receive the feeding progression algorithm were identified via electronic medical record retrospective chart review. RESULTS: Eighteen completed the study. Compared to the control group, infants receiving feeding interventions had delayed sequencing initiation, extended time between initially off positive pressure ventilation and initiation of sequencing, and decreased feeding-related length of stay, with similar total length of stay. IMPLICATIONS FOR PRACTICE AND RESEARCH: This study adds to existing research supporting the effectiveness of novel feeding progression algorithms and interventions to support the health and outcomes of infants born prematurely. Future research should focus on implementation studies for feeding progression algorithm integration into standard NICU care.