Toward Nonepitaxial Laser Diodes.

Thin-film organic, colloidal quantum dot, and metal halide perovskite semiconductors are all being pursued in the quest for a wavelength-tunable diode laser technology that does not require epitaxial growth on a traditional semiconductor substrate. Despite promising demonstrations of efficient light-emitting diodes and low-threshold optically pumped lasing in each case, there are still fundamental and practical barriers that must be overcome to reliably achieve injection lasing. This review outlines the historical development and recent advances of each material system on the path to a diode laser. Common challenges in resonator design, electrical injection, and heat dissipation are highlighted, as well as the different optical gain physics that make each system unique. The evidence to date suggests that continued progress for organic and colloidal quantum dot laser diodes will likely hinge on the development of new materials or indirect pumping schemes, while improvements in device architecture and film processing are most critical for perovskite lasers. In all cases, systematic progress will require methods that can quantify how close new devices get with respect to their electrical lasing thresholds. We conclude by discussing the current status of nonepitaxial laser diodes in the historical context of their epitaxial counterparts, which suggests that there is reason to be optimistic for the future.

Autoimmune conditions and gastric cancer risk in a population-based study in the United Kingdom.

BACKGROUND: Although overall incidence of gastric cancer is decreasing, incidence has been increasing among young people in some Western countries. This trend may stem from the increase in autoimmune conditions. METHODS: A nested case-control study of gastric cancer in UK Clinical Practice Research Datalink. Up to ten cancer-free controls were matched to cases by age and sex. Conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI) for associations between analyzable autoimmune conditions (n = 34) and gastric cancer with Bonferroni correction. We evaluated associations between pernicious anaemia and other conditions. A meta-analysis of published prospective studies and ours was conducted. RESULTS: Among 6586 cases (1156 cardia, 1104 non-cardia, and 4334 overlapping/unspecified tumours) and 65,687 controls, any autoimmune condition was associated with gastric cancer (OR = 1.10; 95% CI: 1.01-1.20). Individuals with pernicious anaemia had higher gastric cancer risk than those without (OR = 2.75; 2.19-3.44). Among controls, pernicious anaemia was associated with seven other conditions (OR range: 2.21-29.80). The pooled estimate for any autoimmune condition and gastric cancer was 1.17 (1.14-1.21; n = 47,126 cases). CONCLUSION: Autoimmunity increases gastric cancer risk. Some autoimmune conditions may be indirectly associated with gastric cancer via pernicious anaemia. Pernicious anaemia could be considered for gastric cancer risk stratification and screening.

Prevalence of Gastric Precursor Lesions in Countries With Differential Gastric Cancer Burden: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: The prevalence of precursor lesions for gastric cancer (GC) and the differential burden between countries of varying GC risk is not well-understood. We conducted a systematic review and meta-analysis to estimate the global prevalence of precursor lesions. METHODS: We estimated the prevalence of atrophic gastritis (AG), gastric intestinal metaplasia (IM), and dysplasia in regions with low, medium, and high GC incidence. Because IM is an advanced manifestation of AG, we assessed the prevalence of less advanced precursors, regardless of the presence of more advanced lesions. Prevalence was sub-stratified by Helicobacter pylori infection, symptomatology, and period (<2000, 2000-2010, and >2010). RESULTS: Among the 582 articles that underwent full-text review, 166 studies met inclusion criteria. The global prevalence estimates of AG, IM, and dysplasia were 25.4%, 16.2%, and 2.0%, respectively, on the basis of 126 studies that reported the prevalence of less advanced precursors, regardless of the presence of more advanced lesions. The prevalence of all precursor lesions was higher in high and medium compared with low GC incidence countries (P < .01). Prevalence of AG and IM was significantly higher among H pylori-infected individuals (P < .01) but not statistically different between symptomatic and asymptomatic individuals (P > .17). All precursors demonstrated a secular decrease in prevalence over time. CONCLUSIONS: Gastric precursor lesions have differences in prevalence in regions with differential GC incidence and are associated with H pylori infection. Because of the substantial prevalence of precursor lesions in both symptomatic and asymptomatic individuals, symptomatic evaluation may not be sufficient to identify individuals at risk. These estimates provide important insights for tailoring GC prevention strategies.

Freshwater invertebrate responses to fine sediment stress: A multi-continent perspective.

Excessive fine sediment (particles <2 mm) deposition in freshwater systems is a pervasive stressor worldwide. However, understanding of ecological response to excess fine sediment in river systems at the global scale is limited. Here, we aim to address whether there is a consistent response to increasing levels of deposited fine sediment by freshwater invertebrates across multiple geographic regions (Australia, Brazil, New Zealand and the UK). Results indicate ecological responses are not globally consistent and are instead dependent on both the region and the facet of invertebrate diversity considered, that is, taxonomic or functional trait structure. Invertebrate communities of Australia were most sensitive to deposited fine sediment, with the greatest rate of change in communities occurring when fine sediment cover was low (below 25% of the reach). Communities in the UK displayed a greater tolerance with most compositional change occurring between 30% and 60% cover. In both New Zealand and Brazil, which included the most heavily sedimented sampled streams, the communities were more tolerant or demonstrated ambiguous responses, likely due to historic environmental filtering of invertebrate communities. We conclude that ecological responses to fine sediment are not generalisable globally and are dependent on landscape filters with regional context and historic land management playing important roles.

Organometallic Bridge Diversification of Bicyclo[1.1.1]pentanes.

Bicyclo[1.1.1]pentane (BCP) derivatives have attracted significant recent interest in drug discovery as alkyne, tert-butyl and arene bioisosteres, where their incorporation is frequently associated with increased compound solubility and metabolic stability. While strategies for functionalisation of the bridgehead (1,3) positions are extensively developed, platforms allowing divergent substitution at the bridge (2,4,5) positions remain limited. Recent reports have introduced 1-electron strategies for arylation and incorporation of a small range of other substituents, but are limited in terms of scope, yields or practical complexity. Herein, we show the synthesis of diverse 1,2,3-trifunctionalised BCPs through lithium-halogen exchange of a readily accessible BCP bromide. When coupled with medicinally relevant product derivatisations, our developed 2-electron "late stage" approach provides rapid and straightforward access to unprecedented BCP structural diversity (>20 hitherto-unknown motifs reported). Additionally, we describe a method for the synthesis of enantioenriched "chiral-at-BCP" bicyclo[1.1.1]pentanes through a novel stereoselective bridgehead desymmetrisation.

Radical coupling of aryl halides to arenes facilitated by Ni(COD)(DQ) and other nickel sources.

The air-stable complex Ni(COD)(DQ) (COD = 1,5-cyclooctadiene, DQ = duroquinone) promotes the coupling of aryl halides to arenes in the presence of KOtBu. This complex has recently been shown to perform coupling reactions based on organonickel intermediates, but in this case the coupling reactions proceed via aryl radicals as shown by our newly developed assay for aryl radicals. Coupling with this nickel source is more efficient than with Ni(COD)2, Ni(PPh3)4 and Ni(acac)2, all of which we also show to operate through aryl radical pathways.

An assay for aryl radicals using BHAS coupling.

Aryl radicals are intermediates in many reactions, but determining their presence unambiguously is often challenging. As we recently reported, reaction of 2-iodo-1,3-dimethylbenzene (7) in benzene with KOtBu and a suitable organic additive, leads to a base-induced homolytic aromatic substitution (BHAS) coupling reaction giving 2,6-dimethylbiphenyl (12) and biphenyl (3) as coupled products, together with xylene (13). In this case, biphenyl arises from a radical translocation and is the major coupling product. This paper now quantitatively investigates that reaction, which shows a very similar ratio for 3 : 12 [ca. 4 : 1] when using different sources of radical initiation. Deuterium isotope studies provide detailed mechanistic support for the proposed mechanism; when carried out in C6D6vs. C6H6, the reaction is characterised by a strong isotope effect for formation of 3-d10vs. 3, but not for formation of 12-d5vs. 12. These distinctive properties mean that the transformation can act as an assay for aryl radicals. An advantage of such a BHAS process is its sensitivity, since it involves a chain reaction that can amplify radical activity.

Nitrogen-Centered Radicals in Functionalization of sp2 Systems: Generation, Reactivity, and Applications in Synthesis.

The chemistry of nitrogen-centered radicals (NCRs) has plentiful applications in organic synthesis, and they continue to expand as our understanding of these reactive species increases. The utility of these reactive intermediates is demonstrated in the recent advances in C-H amination and the (di)amination of alkenes. Synthesis of previously challenging structures can be achieved by efficient functionalization of sp2 moieties without prefunctionalization, allowing for faster and more streamlined synthesis. This Review addresses the generation, reactivity, and application of NCRs, including, but not limited to, iminyl, aminyl, amidyl, and aminium species. Contributions from early discovery up to the most recent examples have been highlighted, covering radical initiation, thermolysis, photolysis, and, more recently, photoredox catalysis. Radical-mediated intermolecular amination of (hetero)arenes can occur with a variety of complex amine precursors, generating aniline derivatives, an important class of structures for drug discovery and development. Functionalization of olefins is achievable in high anti-Markovnikov regioselectivity and allows access to difunctionalized structures when the intermediate carbon radicals are trapped. Additionally, the reactivity of NCRs can be harnessed for the rapid construction of N-heterocycles such as pyrrolidines, phenanthridines, quinoxalines, and quinazolinones.

Pasture feeding improves the nutritional, textural and techno-functional characteristics of butter.

There is an increasing consumer desire for pasture-derived dairy products, as outdoor pasture-based feeding systems are perceived as a natural environment for animals. Despite this, the number of grazing animals globally has declined as a result of the higher milk yields achieved by indoor, total mixed ration feeding systems, in addition to the changing climatic conditions and lower grazing knowledge and infrastructure. This has led to the development of pasture-fed standards, stipulating the necessity of pasture and its minimum requirements as the primary feed source for products advertising such claims, with various requirements depending on region for which it was produced. This work investigates the differences in the composition and techno-functional properties of butters produced from high, medium and no pasture allowance diets during early, mid and late lactation. Butters were produced using milks collected from 3 feeding systems: outdoor pasture grazing (GRS; high pasture allowance); indoor total mixed ration (TMR; no pasture allowance); and a partial mixed ration (PMR; medium pasture allowance) system, which involved outdoor pasture grazing during the day and indoor TMR feeding at night. Butters were manufactured during early, mid and late lactation. Creams derived from TMR feeding systems exhibited the highest milk fat globule size. The fatty acid profiles of butters also differed significantly as a function of diet, and could be readily discriminated by partial least squares analysis. The most important fatty acids in such analysis, as indicated by their highest variable importance projection scores, were CLA C18:2 cis-9 trans-11 (rumenic acid), C16:1 n-7 trans (trans-palmitoleic acid), C18:1 trans (elaidic acid), C18:3 n-3 (α-linolenic acid) and C18:2 n-6 (linoleic acid). Increasing pasture allowances resulted in reduced crystallization temperatures and hardness of butters, while concurrently increasing the 'yellow' b* color. Yellow color was strongly correlated with Raman peaks commonly associated with carotenoids. The milk fat globule size of cream decreased with advancing stage of lactation and churning time of cream was lowest in early lactation. Differences in the fatty acid and triglyceride contents of butter as a result of lactation and dietary effects demonstrated significant correlations with the hardness, rheological, melting and crystallization profiles of the butters. This work highlighted the improved nutritional profile and functional properties of butter with increasing dietary pasture allowance, primarily as a result of increasing proportions of unsaturated fatty acids. Biomarkers of pasture feeding (response in milk proportionate to the pasture allowance) associated with the pasture-fed status of butters were also identified as a result of the significant changes in the fatty acid profile with increasing pasture allowance. This was achieved through the use of 3 authentic feeding systems with varying pasture allowances, commonly operated by farmers around the world and conducted across 3 stages of lactation.

Impact of Neighborhood Deprivation and Social Vulnerability on Outcomes and Interventions in Patients with Cleft Palate.

OBJECTIVE: To examine whether neighborhood disadvantage impacts length of follow-up, interventions, and outcomes for patients with cleft palate. DESIGN: Retrospective cohort. SETTING: Cleft Palate Craniofacial Institute Database at St. Louis Children's Hospital. PATIENTS/PARTICIPANTS: Patients with cleft palate following in St. Louis Children's Hospital Cleft Palate Multidisciplinary Team Clinic. INTERVENTIONS: Primary palatoplasty between 2012-2017. Patients were divided into quartiles across area deprivation index (ADI) and social vulnerability index (SVI), two validated, composite metrics of neighborhood disadvantage, to examine whether living in neighborhoods from different deprivation quartiles impacts outcomes of interest. MAIN OUTCOME MEASURE: Follow-up through age 5, surgeries and surgical complications, speech, developmental, and behavioral outcomes. RESULTS: 205 patients were included. 39% of patients belonged to the most deprived ADI quartile, while 15% belonged to the most vulnerable SVI quartile. There were no differences between ADI or SVI quartiles in number of operations received (p ≥ 0.40). Patients in the most deprived ADI quartile were significantly more likely to have speech/language concerns (OR 2.32, 95% CI [1.20-4.89], p = 0.01). Being in a more vulnerable SVI quartile was associated with developmental delay (OR 2.29, 95% CI [1.04-5.15], p = 0.04). ADI and SVI quartile did not impact risk of loss to follow-up in the isolated and combined cleft lip and palate subgroups (p ≥ 0.21). CONCLUSIONS: Neighborhood disadvantage impacts speech and developmental outcomes in patients with cleft palate despite comparable length of follow-up in multidisciplinary team clinic.

A Hierarchy of Ligands Controls Formation and Reaction of Aryl Radicals in Pd-Catalyzed Ground-State Base-Promoted Coupling Reactions.

Palladium salts and complexes were tested separately and in the presence of added ligands as potential sources of aryl radicals in ground-state coupling reactions of aryl halide with arenes under basic conditions (KOtBu). Our recently developed assay for aryl radicals was employed to test for aryl radicals. In this assay, aryl radicals derived from the test substrate, 1-iodo-2,6-dimethylbenzene 7, undergo base-promoted homolytic aromatic substitution (BHAS) with benzene to produce 2,6-dimethylbiphenyl 8 and biphenyl 9 in an approximately 1:4 ratio as well as m-xylene 10. The biphenyl arises from a diagnostic radical transfer reaction with the solvent benzene. Using substrate 7 with a range of Pd sources as potential initiators led to formation of 8, 9, and 10 in varying amounts. However, when any one of a range of diphosphinoferrocenes (e.g., dppf or dippf) or BINAP or the monophosphine, diphenylphosphinoferrocene, was added as a ligand to Pd(OAc)2, the ratio of [2,6-dimethylbiphenyl 8: biphenyl 9] moved decisively to that expected from the BHAS (radical) pathway. Further studies were conducted with dppf. When dppf was added to each of the other Pd sources, the ratio of coupled products was also diverted to that expected for radical BHAS chemistry. Deuterium isotope studies and radical trap experiments provide strong additional support for the involvement of aryl radicals. Accordingly, under these ground-state conditions, palladium sources, in the presence of defined ligands, convert aryl iodides to aryl radicals. A rationale is proposed for these observations.

Interfacial Chemistry Effects in the Electrochemical Performance of Silicon Electrodes under Lithium-Ion Battery Conditions.

Understanding the solid electrolyte interphase (SEI) formation and (de)lithiation phenomena at silicon (Si) electrodes is key to improving the performance and lifetime of Si-based lithium-ion batteries. However, these processes remain somewhat elusive, and, in particular, the role of Si surface termination merits further consideration. Here, scanning electrochemical cell microscopy (SECCM) is used in a glovebox, followed by secondary ion mass spectrometry (SIMS) at identical locations to study the local electrochemical behavior and associated SEI formation, comparing Si (100) with a native oxide layer (SiOx /Si) and etched with hydrofluoric acid (HF-Si). HF-Si shows greater spatial electrochemical heterogeneity and inferior lithiation reversibility than SiOx /Si. This is attributed to a weakly passivating SEI and irreversible lithium trapping at the Si surface. Combinatorial screening of charge/discharge cycling by SECCM with co-located SIMS reveals SEI chemistry as a function of depth. While the SEI thickness is relatively independent of the cycle number, the chemistry - particularly in the intermediate layers - depends on the number of cycles, revealing the SEI to be dynamic during cycling. This work serves as a foundation for the use of correlative SECCM/SIMS as a powerful approach to gain fundamental insights on complex battery processes at the nano- and microscales.

Association of genital talc and douche use in early adolescence or adulthood with uterine fibroids diagnoses.

BACKGROUND: Genital talc and douching are practices that can involve exposure to chemical compounds linked to certain gynecologic cancers. However, it is unclear if they are associated with fibroid risk or age at fibroid diagnosis among women. OBJECTIVE: This study aimed to evaluate the impact of early-adolescence genital talc use and douching on prevalence of fibroids diagnosed before the age of 35 and 50 years among Black/African American and non-Hispanic White women. STUDY DESIGN: Data were derived from the Sister Study (2003-2020), a prospective cohort of 50,884 US women aged 35 to 74 years at enrollment. Participants were asked if they ever had a fibroid diagnosis and at what age, and if they used genital talc and/or douched between the ages of 10 and 13 years or in the past 12 months. After applying predefined exclusion criteria, our analytical sample size was n=46,316 (Black, n=4310; non-Hispanic White, n=42,006). Multivariable logistic regression was used to compute adjusted odds ratios and 95% confidence intervals for having vs not having early-onset fibroids diagnosed before age 35 among women aged 35 to 74 years at enrollment, and fibroids diagnosed before age 50 among women aged 50 to 74 years at enrollment. We adjusted for early life factors (in utero diethylstilbestrol exposure, singleton or multiple birth, fed soy formula during infancy), childhood socioeconomic status, and relative weight and height compared with peers at age 10. We used multiple imputation (<10% missing in all analyses). Results were stratified by race/ethnicity given that Black women are more likely to develop fibroids at a younger age than non-Hispanic White women. RESULTS: Among Black/African American women, 29% had fibroids diagnosed before age 35. Both genital talc use at age 10 to 13 (adjusted odds ratio, 1.23; confidence interval, 1.06-1.41) and douching (adjusted odds ratio, 1.19; 95% confidence interval, 0.95-1.48) were associated with higher odds of having a fibroid diagnosed before age 35. Douching without talc use was not associated with increased odds, but combined use of genital talc and douche was associated with 52% increased odds of fibroids (confidence interval, 1.14-2.01). Among non-Hispanic White women, 9% reported fibroids diagnosed before age 35. Genital talc use (1.31; 1.20-1.44) but not douching (0.96; 0.77-1.20) at age of 10 to 13 years was associated with having a fibroid diagnosed before age 35. We observed similar patterns for non-Hispanic White women when we considered fibroids diagnosed before age 50, but neither practice was associated with fibroids diagnosed before age 50 in Black women. CONCLUSION: Genital talc use in early adolescence, alone and in combination with douching (but not douching alone), is associated with prevalence of fibroids diagnosed before age 35 among Black/African American women and before ages 35 and 50 among non-Hispanic White women. Early adolescence may be a window of susceptibility for fibroid development, suggesting that adolescent girls should be educated on abstention from or alternatives to talc use and douching.

Review of cardiovascular imaging in the Journal of Nuclear Cardiology 2022: positron emission tomography, computed tomography, and magnetic resonance.

In 2022, the Journal of Nuclear Cardiology® published many excellent original research articles and editorials focusing on imaging in patients with cardiovascular disease. In this review of 2022, we summarize a selection of articles to provide a concise recap of major advancements in the field. In the first part of this 2-part series, we addressed publications pertaining to single-photon emission computed tomography. In this second part, we focus on positron emission tomography, cardiac computed tomography, and cardiac magnetic resonance. We specifically review advances in imaging of non-ischemic cardiomyopathy, cardio-oncology, infectious disease cardiac manifestations, atrial fibrillation, detection and prognostication of atherosclerosis, and technical improvements in the field. We hope that this review will be useful to readers as a reminder to articles they have seen during the year as well as ones they have missed.

Uptake and efficacy of bilateral risk reducing surgery in unaffected female BRCA1 and BRCA2 carriers.

BACKGROUND: Women testing positive for BRCA1/2 pathogenic variants have high lifetime risks of breast cancer (BC) and ovarian cancer. The effectiveness of risk reducing surgery (RRS) has been demonstrated in numerous previous studies. We evaluated long-term uptake, timing and effectiveness of risk reducing mastectomy (RRM) and bilateral salpingo-oophorectomy (RRSO) in healthy BRCA1/2 carriers. METHODS: Women were prospectively followed up from positive genetic test (GT) result to censor date. χ² testing compared categorical variables; Cox regression model estimated HRs and 95% CI for BC/ovarian cancer cases associated with RRS, and impact on all-cause mortality; Kaplan-Meier curves estimated cumulative RRS uptake. The annual cancer incidence was estimated by women-years at risk. RESULTS: In total, 887 women were included in this analysis. Mean follow-up was 6.26 years (range=0.01-24.3; total=4685.4 women-years). RRS was performed in 512 women, 73 before GT. Overall RRM uptake was 57.9% and RRSO uptake was 78.6%. The median time from GT to RRM was 18.4 months, and from GT to RRSO-10.0 months. Annual BC incidence in the study population was 1.28%. Relative BC risk reduction (RRM versus non-RRM) was 94%. Risk reduction of ovarian cancer (RRSO versus non-RRSO) was 100%. CONCLUSION: Over a 24-year period, we observed an increasing number of women opting for RRS. We showed that the timing of RRS remains suboptimal, especially in women undergoing RRSO. Both RRM and RRSO showed a significant effect on relevant cancer risk reduction. However, there was no statistically significant RRSO protective effect on BC.

A three-year comparison of once-a-day and twice-a-day milking in seasonal-calving pasture-based systems.

Globally, the majority of dairy cows are milked twice a day (TAD); however, in pasture-based production systems, such as in Ireland, the idea of milking once a day (OAD) is being considered for reasons such as improved work-life balance. The immediate effects within a lactation, as well as the multilactation consequences of OAD, compared with TAD milking, require understanding. The objective of this randomized experiment was to compare OAD and TAD milking, over a 3-yr period, by examining the differences in milk production and composition, body weight (BW), body condition score (BCS), dry matter intake (DMI), udder characteristics, locomotion score, and milking time. Over the 3-yr period, 83 cows were enrolled in the experiment; 32, 44, and 48 cows in yr 1, 2, and 3 of the experiment, respectively. Each year, 23% of the herds were primiparous animals, while the remainder were second lactation or greater in parity. All cows were milked in the morning at 0700 h; only cows milked TAD were milked a second time each day at 1600 h. Cows rotationally grazed pastures for the duration of the lactating period and were housed during the nonlactating period. Milking cows OAD reduced cumulative milk yield by 26%, and milk solids yield (kg of fat + kg of protein) by 21%, across the 3 yr of the experiment when compared with cows milked TAD which produced 4,126 and 365 kg/cow, respectively. A contributory factor to the reduced production was a shorter lactation length (9.7 d) of the cows milked OAD compared with TAD (294 d). Milk fat percent of cows milked TAD was similar for all 3 yr of the study (5.05%), whereas milk fat percent of the cows milked OAD increased year on year, with each year being greater than the previous year (5.02%, 5.32%, and 5.70% for yr 1, 2, and 3; respectively). Milk protein percent was greater (+0.19%) for cows milked OAD compared with TAD which was 3.78%. Compared with cows milked TAD, total DMI for cows milked OAD was 22% less at the start of lactation (<167 d), but as the lactation progressed (>167 d) we observed no difference in DMI between treatments. Similar to the literature, milking cows OAD significantly increased average somatic cell score, both during (+16%) and at the end of lactation (+19%), compared with milking cows TAD which were 4.69 and 4.79, respectively. We detected positive aspects associated with OAD milking such as greater BW, BCS, and fertility performance. Milking OAD reduced both milking time per cow per day (reductions ranged from 34% in the first 4 mo of lactation to 43% during mo 5-9 of lactation) and milking time per liter of milk (-3.5 s/L) throughout lactation, leading to less labor inputs on-farm which can have positive implications for farmer work-life balance. The significant time saving and potential savings in costs (e.g., electricity) need to be considered in conjunction with the milk production reduction when considering OAD milking for the entire lactation.

Impact of varying levels of pasture allowance on the nutritional quality and functionality of milk throughout lactation.

The objective of this study was to examine the impact of increasing proportions of grazed pasture in the diet on the composition, quality, and functionality of bovine milk across a full lactation. Fifty-four spring-calving cows were randomly assigned to 1 of 3 groups (n = 18), blocked on the basis of mean calving date (February 15, 2020 ± 0.8 d), pre-experimental daily milk yield (24.70 ± 3.70 kg), milk solids yield (2.30 ± 0.27 kg), lactation number (3.10 ± 0.13), and economic breeding index (182 ± 19). Raw milk samples were obtained weekly from each group between March and November 2020. Group 1 (GRS) consumed perennial ryegrass and was supplemented with 5% concentrates (dry matter basis); group 2 was maintained indoors and consumed a total mixed ration (TMR) diet consisting of maize silage, grass silage, and concentrates; and group 3 consumed a partial mixed ration diet (PMR), rotating between perennial ryegrass during the day and indoor TMR feeding at night. Raw milk samples consisted of a pooled morning and evening milking and were analyzed for gross composition, free amino acids, fatty acid composition, heat coagulation time, color, fat globule size, and pH. The TMR milks had a significantly higher total solids, lactose, protein, and whey protein as a proportion of protein content compared with both GRS and PMR milks. The GRS milks demonstrated a significantly lower somatic cell count (SCC), but a significantly higher pH and b*-value than both TMR and PMR milks. The PMR milks exhibited significantly lower total solids and fat content, but also demonstrated significantly higher SCC and total free amino acid content compared with GRS and TMR. Partial least squares discriminant analysis of fatty acid profiles displayed a distinct separation between GRS and TMR samples, while PMR displayed an overlap between both GRS and TMR groupings. Variable importance in projection analysis identified conjugated linoleic acid cis-9,trans-11, C18:2n-6 cis, C18:3n-3, C11:0, and C18:2n-6 trans as the largest contributors to the variation between the diets. Milk fats derived from GRS diets exhibited the highest proportion of unsaturated fats and higher unsaturation, health-promoting, and desaturase indices. The lowest proportions of saturated fats and the lowest atherogenic index were also exhibited by GRS-derived milk fats. This work highlights the positive influence of grass-fed milk for human consumption through its more nutritionally beneficial fatty acid profile, despite the highest milk solid percentages derived from TMR feeding systems. Furthermore, this study demonstrates the proportional response of previously highlighted biomarkers of pasture feeding to the proportion of pasture in the cow's diet.

RNA-Binding Proteins and Their Emerging Roles in Cancer: Beyond the Tip of the Iceberg.

RNA-binding proteins (RBPs) represent a large family of proteins with an extensive array of roles that contribute to coordinating and directing multiple functions in RNA metabolism and transcription [...].

Family Experiences with Diagnosis of Craniosynostosis: Thematic Analysis of Online Discussion Boards.

OBJECTIVE: Apply thematic analysis of online discussion boards to characterize families' experiences and concerns regarding craniosynostosis diagnoses to aid physicians in tailoring care to families. DESIGN: Grounded theory-based qualitative analysis. SETTING: Discussion boards related to craniosynostosis identified via Google and Yahoo. PATIENTS/PARTICIPANTS: Posts about craniosynostosis between 2017-2022. INTERVENTIONS: Thematic analysis was performed using three rounds of coding. Post features including author type and use of technical language were examined. MAIN OUTCOME MEASURE: Overarching themes emerging from analysis of posts, with forums analyzed until sufficient thematic repetition was observed. RESULTS: 366 posts from 4 websites by 290 unique users were included. Parents of patients with craniosynostosis wrote 59% of posts while patients wrote 4%. Five selective codes were identified: 1) Building Community, 2) Diagnosis/Evaluation, 3) Treatment, 4) Outcomes, and 5) Emotional Concerns. Building Community was the most assigned code (85% of posts). 71% of parents' posts expressing emotional concerns expressed negative emotions, commonly regarding anxiety about diagnosis (71%), frustration about doctors' responses (21%), or negative reactions to online search results (17%). 88% of patients' posts expressed positive emotions, discussing positive long-term outcomes. Concerns that may guide physicians included anxiety about delayed diagnosis, difficulty distinguishing postpartum head shape changes from craniosynostosis, and difficulty finding a care team. CONCLUSIONS: Online discussion boards allow families of patients with craniosynostosis to share experiences and find community. Improving communication between surgeons, pediatricians, and families about timing of evaluation and revising online information about this condition may ameliorate some anxiety associated with this diagnosis.