Nanoparticle-mediated thermal Cancer therapies: Strategies to improve clinical translatability.

Despite significant advances, cancer remains a leading global cause of death. Current therapies often fail due to incomplete tumor removal and nonspecific targeting, spurring interest in alternative treatments. Hyperthermia, which uses elevated temperatures to kill cancer cells or boost their sensitivity to radio/chemotherapy, has emerged as a promising alternative. Recent advancements employ nanoparticles (NPs) as heat mediators for selective cancer cell destruction, minimizing damage to healthy tissues. This approach, known as NP hyperthermia, falls into two categories: photothermal therapies (PTT) and magnetothermal therapies (MTT). PTT utilizes NPs that convert light to heat, while MTT uses magnetic NPs activated by alternating magnetic fields (AMF), both achieving localized tumor damage. These methods offer advantages like precise targeting, minimal invasiveness, and reduced systemic toxicity. However, the efficacy of NP hyperthermia depends on many factors, in particular, the NP properties, the tumor microenvironment (TME), and TME-NP interactions. Optimizing this treatment requires accurate heat monitoring strategies, such as nanothermometry and biologically relevant screening models that can better mimic the physiological features of the tumor in the human body. This review explores the state-of-the-art in NP-mediated cancer hyperthermia, discussing available nanomaterials, their strengths and weaknesses, characterization methods, and future directions. Our particular focus lies in preclinical NP screening techniques, providing an updated perspective on their efficacy and relevance in the journey towards clinical trials.

Genomic evaluation of late-term abortion in cows recorded through Dairy Herd Improvement test plans.

Late-term abortions cause significant economic loss and are of great concern for dairy herds. Late-term abortions >152 d and <251 d of gestation that terminate a lactation or initiate a new lactation have long been recorded by Dairy Herd Improvement (DHI). For 24.8 million DHI lactations, the average recorded incidence of late-term abortions across all years (2001-2018) was 1.2%. However, the 1.3% incidence of abortions reported in 2012 has declined to <1.0% incidence since 2015. Small adjustments were applied to the 82 million daughter pregnancy rate (DPR), 29 million cow conception rate (CCR), and 9 million heifer conception rate (HCR) records to account for late-term abortions more accurately. Fertility credits for CCR and HCR were changed to treat the last breeding as a failure instead of success if the next calving was coded as a late-term abortion. Similarly, when computing DPR, days open is now set to the maximum value of 250 instead of the reported days open if the next reported calving is an abortion. The test of these changes showed very small changes in standard deviation and high correlations (0.997) of adjusted predicted transmitting abilities (PTA) with official PTA from about 20,000 Holstein bulls born since 2000 with >50% reliability. For late-term abortion as a trait, estimated heritability was only 0.001 and PTA had a standard deviation of only 0.1% for recent sires with high reliability (>75%). Young animal genomic PTA have near 50% reliability but range only from -0.5 to +0.4 because of the low incidence and heritability. Genetic trend was slightly favorable and late-term abortion PTA were correlated favorably by 0.27 with net merit, 0.49 with productive life, 0.33 with livability, 0.23 with CCR, 0.20 with HCR, 0.26 with DPR, -0.31 with somatic cell score, -0.24 with daughter stillbirth, and -0.26 with daughter dystocia. Thus, PTA for late-term abortions should not be needed as a separate fertility trait and instead these minor edit changes should suffice. The PTA for late-term abortions would add little value because national evaluations for current fertility traits already account for those economic losses.

The World Organisation for Animal Health - current and potential roles in safe international trade of bees and other insects.

The World Organisation for Animal Health (WOAH, founded as OIE) is the recognised intergovernmental standard-setting organisation for animal health and welfare. The WOAH mandate is to support its members in the prevention of the spread of animal diseases of concern, as listed in the Terrestrial Animal Health Code (Terrestrial Code). Once a disease, infection or infestation is listed, national Veterinary Authorities have the obligation regularly to notify WOAH of the presence or absence of the listed disease. In regard to insects, the scope of the Terrestrial Code limits its recommendations to preserving the health of bees (species of the genus Apis, extended to the genus Bombus and to the stingless bees for one disease). However, it does not include standards to mitigate the potential animal health risks associated with the international trade of other insects. A description of the standard-setting process and a review of the history of the standards for bee health highlight the resources and requirements to expand the scope of the Terrestrial Code to include recommendations for animal health risk mitigation measures for the safety of international trade in insects. Any initiative to develop guidance on insect trade should include WOAH in its role as the sole global standard-setting organisation on animal health and welfare matters. This aligns with the WOAH commitment to a One Health approach.

L'Organisation mondiale de la santé animale (OMSA, fondée en tant qu'OIE) est l'organisation inter-gouvernementale reconnue pour l'élaboration de normes relatives à la santé et au bien-être des animaux. L'OMSA a pour mandat d'apporter un soutien à ses Membres afin de prévenir la propagation des maladies animales d'importance majeure listées dans le Code sanitaire pour les animaux terrestres (Code terrestre). Dès lors qu'une maladie, une infection ou une infestation figure sur cette liste, les Autorités vétérinaires ont l'obligation de notifier régulièrement à l'OMSA la présence ou l'absence de cette maladie sur leur territoire. S'agissant des insectes, le champ d'application du Code terrestre limite ses recommandations à la préservation de la santé des abeilles (espèces du genre Apis, avec l'inclusion du genre Bombus et des abeilles sans dard pour une maladie). Néanmoins, le Code terrestre ne contient pas de normes visant à atténuer les risques pour la santé animale associés aux échanges internationaux d'autres insectes. La description faite par les auteurs du processus d'élaboration des normes et leur aperçu rétrospectif de la mise au point des normes relatives à la santé des abeilles font ressortir les ressources et les conditions nécessaires pour élargir le champ d'application du Code terrestre afin d'y inclure des recommandations portant sur les mesures d'atténuation des risques pour la santé animale applicables à la sécurité sanitaire des échanges internationaux d'insectes. Toute initiative visant à fournir des orientations sur les échanges d'insectes devrait inclure l'OMSA dans son rôle d'unique organisation chargée de l'élaboration des normes internationales relatives à la santé animale et au bien-être des animaux. Cette exigence est en cohérence avec l'engagement de l'OMSA en faveur de l'approche Une seule santé.

La Organización Mundial de Sanidad Animal (OMSA, fundada como OIE) es la organización intergubernamental facultada para ejercer funciones normativas en materia de sanidad y bienestar de los animales. La OMSA tiene por mandato ayudar a sus miembros a prevenir la propagación de una serie de enfermedades animales de importancia, recogidas en el Código Sanitario para los Animales Terrestres (Código Terrestre) de la OMSA. La inclusión de una enfermedad, infección o infestación en la lista de la OMSA obliga a las autoridades veterinarias nacionales a dar cuenta periódicamente a la OMSA de la presencia o ausencia de esa patología en su territorio. Por lo que respecta a los insectos, en el Código Terrestre solo se formulan una serie de recomendaciones para proteger la salud de las abejas (categoría que corresponde a las especies del género Apis, extensible también al género Bombus y, en el caso de una enfermedad, a las abejas sin aguijón). El Código Terrestre, sin embargo, no contiene norma alguna destinada a mitigar los posibles riesgos zoosanitarios ligados al comercio internacional de otros insectos. Los autores describen el proceso normativo y repasan la historia de las normas relativas a la sanidad de las abejas, con lo que ponen de relieve los recursos y demás elementos necesarios para conferir mayor alcance al Código Terrestre incluyendo en él recomendaciones sobre medidas de mitigación del riesgo zoosanitario para un comercio seguro de insectos a escala internacional. Toda iniciativa encaminada a marcar pautas sobre el comercio de insectos debería incluir a la OMSA, única organización con potestad normativa mundial sobre temas de sanidad y bienestar de los animales, lo que además se encuadra en el compromiso de la OMSA con los planteamientos de «Una sola salud¼.

Geometric morphometrics and anatomical network analyses reveal ecospace partitioning among geoemydid turtles from the Uinta Formation, Utah.

We present new fossil records of the geoemydid turtle Bridgeremys pusilla from the Uinta Formation of Utah. Turtles are abundant throughout the unit, and known taxa are similar to those from the older strata in the Upper Green River Basin in Wyoming from the Bridger and Washakie Formations. B. pusilla is known from Bridgerian deposits but was not previously known from after the Turtle Bluff Member of the Bridger Formation. The taxon was coveal with two species of the geoemydid Echmatemys (E. callopyge and E. wyomingensis), a common genus of extinct pond turtles known primarily from lacustrine and fluvial deposits in western North America, including the Uinta Basin. In addition to previously documented morphological differences, our geometric morphometric analyses revealed significant differences in epiplastral morphology between B. pusilla and the two coeval Echmatemys species. Bridgeremys pusilla shared several morphological characters with Testudinidae. However, our anatomical network analysis suggests that the carapace of B. pusilla distributed stress forces in a manner more similar to emydids (basal and derived) than to derived testudinoids (Testudinidae and Emydidae), including Echmatemys species. This finding changes our understanding of the ecology of the species and sheds light onto how geoemydid turtles of the Uinta Formation may have partitioned the available ecospace. These new Uintan records extend the geographic range of B. pusilla into the Uinta Basin and stratigraphically through the top of the Uinta Formation, extending the temporal range of the taxon by more than 4 million years through the Uintan North American Land Mammal Age to the base of the Duchesne River Formation.

Genomic evaluation of dairy heifer livability.

Differences in breeds and sire lines suggest the presence of a genetic component for heifer livability (HLIV). Genomic evaluation for this trait can increase profitability and improve animal health and welfare. Evaluations for HLIV were examined from 3,362,499 calf data records from heifers of all breeds born from 2009 to 2016. Data were obtained from the national cooperator database maintained by the Council on Dairy Cattle Breeding (https://www.uscdcb.com/). The total number of deaths reported was 134,753 (4.01%), which included herds with death loss between 1.5 and 25.5%. Age at death was evaluated and ranged from >2 d of age until the heifer left the herd, with a maximum of 18 mo of age. Records were not included until 3 yr after the birthdate so that live status of contemporaries could be confirmed by a calving date for those animals. Deaths observed until 2 d after birth were considered to be a stillbirth rather than a failure of HLIV. The scale used for analysis of HLIV was 0 (died) or 100 (live), and the heritability estimate was 0.7% based on sire model with restricted maximum likelihood estimation. Genomic predicted transmitting abilities for Holstein ranged from -1.6% to +1.6% with a standard deviation of 0.5%, and genomic predicted transmitting abilities for Jersey ranged from -0.5% to +0.5% with a standard deviation of 0.2%. The mean overall death loss was about 4%. Reliabilities of genomic predictions for young animals averaged 46% for Holsteins and 30% for Jerseys, and corresponding traditional parent average reliabilities averaged 16% and 12%, respectively. Correlations of HLIV were 0.44 with productive life, 0.18 to 0.22 with yield traits, and 0.29 with early first calving on proven Holstein bulls. The HLIV trait had a favorable genetic trend in recent years, likely because of the indirect selection associated with the correlated traits. The trait HLIV should receive 1% of emphasis on the Lifetime Net Merit index, resulting in economic progress worth $50,000/yr. By encouraging more comprehensive recording on calf mortality, the reliabilities of genetic predictions could increase significantly.

Investigating conception rate for beef service sires bred to dairy cows and heifers.

The widespread use of sexed semen on US dairy cows and heifers has led to an excess of replacement heifers' calves, and the sale prices for those calves are much lower than in the past. Females not selected to produce the next generation of replacement heifers are increasingly being bred to beef bulls to produce crossbred calves for beef production. The purpose of this study was to investigate the use of beef service sires bred to dairy cows and heifers and to provide a tool for dairy producers to evaluate beef service sires' conception. Sire conception rate (SCR) is a phenotypic evaluation of service sire fertility that is routinely calculated for US dairy bulls. A total of 268,174 breedings were available, which included 36 recognized beef breeds and 7 dairy breeds. Most of the beef-on-dairy inseminations (95.4%) were to Angus (AN) bulls. Because of the limited number of records among other breeds, we restricted our final evaluations to AN service sires bred to Holstein (HO) cows. Service-sire inbreeding and expected inbreeding of resulting embryo were set to zero because pedigree data for AN bulls were unavailable. There were 233,379 breedings from 1,344 AN service sire to 163,919 HO cows. A mean (SD) conception rate of 33.8% (47.3%) was observed compared with 34.3% (47.5%) for breedings with HO sires mated to HO cows. Publishable AN bulls were required to have ≥100 total matings, ≥10 matings in the most recent 12 mo, and breedings in at least 5 herds. Mean SCR reliability was 64.5% for 116 publishable bulls, with a maximum reliability of 99% based on 25,217 breedings. Average SCR was near zero (on AN base) with a range of -5.1 to 4.4. Breedings to HO heifers were also examined, which included 19,437 breedings (443 AN service sire and 15,971 HO heifers). A mean (SD) conception rate of 53.0% (49.9%) was observed, compared with 55.3% (49.7%) for breedings with a HO sire mated to a HO heifer. Beef sires were used more frequently in cows known to be problem breeders, which explains some of the difference in conception rate. Mean service number was 1.92 and 2.87 for HO heifers and 2.13 and 3.04 for HO cows mated to HO and AN sires, respectively. Mating dairy cows and heifers to beef bulls may be profitable if calf prices are higher, fertility is improved, or if practices such as sexed semen, genomic testing, and improved cow productive life allow herd owners to produce both higher quality dairy replacement and increased income from market calves.

Additional records and stratigraphic distribution of the middle Eocene carettochelyid turtle Anosteira pulchra from the Uinta Formation of Utah, North America.

BACKGROUND: Anosteira pulchra is one of two species of the obligately-aquatic freshwater clade Carettochelyidae (pig-nosed turtles) from the Eocene of North America. Anosteira pulchra is typically rare in collections, and their distribution is poorly documented. The Uinta Formation [Fm.] contains a diverse assemblage of turtles from the Uintan North American Land Mammal Age. Whereas turtles are abundantly preserved in the Uinta Fm., A. pulchra has been reported only from a few specimens in the Uinta C Member. METHODS: We describe new records of Anosteira pulchra from the Uinta Basin and analyze the distribution of 95 specimens from multiple repositories in the previously published stratigraphic framework of the middle and upper Uinta Fm. RESULTS: Here we report the first records of the species from the Uinta B interval, document it from multiple levels within the stratigraphic section and examine its uncommon appearance in only approximately 5% of localities where turtles have been systematically collected. This study details and extends the range of A. pulchra in the Uinta Fm. and demonstrates the presence of the taxon in significantly lower stratigraphic layers. These newly described fossils include previously unknown elements and associated trace fossils, with new anatomical information presented. This study provides insight into the taxonomy of Anosteira spp. in the middle Eocene, and suggests the presence of a single species, though no synonymy is defined here due to limits in Bridger material.

High-density genome-wide association study for residual feed intake in Holstein dairy cattle.

Improving feed efficiency (FE) of dairy cattle may boost farm profitability and reduce the environmental footprint of the dairy industry. Residual feed intake (RFI), a candidate FE trait in dairy cattle, can be defined to be genetically uncorrelated with major energy sink traits (e.g., milk production, body weight) by including genomic predicted transmitting ability of such traits in genetic analyses for RFI. We examined the genetic basis of RFI through genome-wide association (GWA) analyses and post-GWA enrichment analyses and identified candidate genes and biological pathways associated with RFI in dairy cattle. Data were collected from 4,823 lactations of 3,947 Holstein cows in 9 research herds in the United States. Of these cows, 3,555 were genotyped and were imputed to a high-density list of 312,614 SNP. We used a single-step GWA method to combine information from genotyped and nongenotyped animals with phenotypes as well as their ancestors' information. The estimated genomic breeding values from a single-step genomic BLUP were back-solved to obtain the individual SNP effects for RFI. The proportion of genetic variance explained by each 5-SNP sliding window was also calculated for RFI. Our GWA analyses suggested that RFI is a highly polygenic trait regulated by many genes with small effects. The closest genes to the top SNP and sliding windows were associated with dry matter intake (DMI), RFI, energy homeostasis and energy balance regulation, digestion and metabolism of carbohydrates and proteins, immune regulation, leptin signaling, mitochondrial ATP activities, rumen development, skeletal muscle development, and spermatogenesis. The region of 40.7 to 41.5 Mb on BTA25 (UMD3.1 reference genome) was the top associated region for RFI. The closest genes to this region, CARD11 and EIF3B, were previously shown to be related to RFI of dairy cattle and FE of broilers, respectively. Another candidate region, 57.7 to 58.2 Mb on BTA18, which is associated with DMI and leptin signaling, was also associated with RFI in this study. Post-GWA enrichment analyses used a sum-based marker-set test based on 4 public annotation databases: Gene Ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, Reactome pathways, and medical subject heading (MeSH) terms. Results of these analyses were consistent with those from the top GWA signals. Across the 4 databases, GWA signals for RFI were highly enriched in the biosynthesis and metabolism of amino acids and proteins, digestion and metabolism of carbohydrates, skeletal development, mitochondrial electron transport, immunity, rumen bacteria activities, and sperm motility. Our findings offer novel insight into the genetic basis of RFI and identify candidate regions and biological pathways associated with RFI in dairy cattle.

Defining the optimal period length and stage of growth or lactation to estimate residual feed intake in dairy cows.

Residual feed intake (RFI) is an estimate of animal feed efficiency, calculated as the difference between observed and expected feed intake. Expected intake typically is derived from a multiple regression model of dry matter intake on energy sinks, including maintenance and growth in growing animals, or maintenance, gain in body reserves, and milk production in lactating animals. The best period during the production cycle of a dairy cow to estimate RFI is not clear. Here, we characterized RFI in growing Holstein heifers (RFIGrowth; ∼10 to 14 mo of age; n = 226) and cows throughout a 305-d lactation (RFILac-Full; n = 118). The goals were to characterize relationships between RFI estimated at different production stages of the dairy cow; determine effects of selection for efficiency during growth on subsequent lactation and feed efficiency; and identify the most desirable testing scheme for RFILac-Full. For RFIGrowth, intake was predicted from multiple linear regression of metabolizable energy (ME) intake on mid-test body weight (BW)0.75 and average daily gain (ADG). For RFILac-Full, predicted intake was based on regression of BW0.75, ADG, and energy-corrected milk yield. Mean energy intake of the least and most efficient growing heifers (±0.5 standard deviations from mean RFIGrowth of 0) differed by 3.01 Mcal of ME/d, but the groups showed no difference in mid-test BW or ADG. Phenotypic correlation between RFIGrowth and RFI of heifers estimated in the first 100 d in milk (RFILac100DIM; n = 130) was 0.37. Ranking of these heifers as least (mean + 0.5 standard deviations), middle, or most efficient (mean - 0.5 standard deviations) based on RFIGrowth resulted in 43% maintaining the same ranking by RFILac100DIM. On average, the most efficient heifers ate 3.27 Mcal of ME/d less during the first 100 DIM than the least efficient heifers, but exhibited no differences in average energy-corrected milk yield, ADG, or BW. The correlation between RFILac100DIM and RFILac-Full was 0.72. Thus, RFIGrowth may serve as an indicator trait for RFI during lactation, and selection for heifers exhibiting low RFIGrowth should improve overall herd feed efficiency during lactation. Correlation analysis between RFILac-Full (10 to 305 DIM) and subperiod estimates of RFI during lactation indicated a test period of 64 to 70 d in duration occurring between 150 to 220 DIM provided a reliable approximation (r ≥ 0.90) of RFILac-Full among the test periods evaluated.

The most complete enantiornithine from North America and a phylogenetic analysis of the Avisauridae.

The most complete known North American enantiornithine was collected in 1992 but never formally described. The so-called "Kaiparowits avisaurid" remains one of the most exceptional Late Cretaceous enantiornithine fossils. We recognize this specimen as a new taxon, Mirarce eatoni (gen. et sp. nov.), and provide a complete anatomical description. We maintain that the specimen is referable to the Avisauridae, a clade previously only known in North America from isolated tarsometatarsi. Information from this specimen helps to clarify evolutionary trends within the Enantiornithes. Its large body size supports previously observed trends toward larger body mass in the Late Cretaceous. However, trends toward increased fusion of compound elements across the clade as a whole are weak compared to the Ornithuromorpha. The new specimen reveals for the first time the presence of remige papillae in the enantiornithines, indicating this feature was evolved in parallel to dromaeosaurids and derived ornithuromorphs. Although morphology of the pygostyle and (to a lesser degree) the coracoid and manus appear to remain fairly static during the 65 million years plus of enantiornithine evolution, by the end of the Mesozoic at least some enantiornithine birds had evolved several features convergent with the Neornithes including a deeply keeled sternum, a narrow furcula with a short hypocleidium, and ulnar quill knobs-all features that indicate refinement of the flight apparatus and increased aerial abilities. We conduct the first cladistic analysis to include all purported avisuarid enantiornithines, recovering an Avisauridae consisting of a dichotomy between North and South American taxa. Based on morphological observations and supported by cladistic analysis, we demonstrate Avisaurus to be paraphyletic and erect a new genus for "A. gloriae," Gettyia gen. nov.

Comparison of false-negative rates and limits of detection following macrofoam-swab sampling of Bacillus anthracis surrogates via Rapid Viability PCR and plate culture.

AIMS: We evaluated the effects of Bacillus anthracis surrogates, low surface concentrations, surface materials and assay methods on false-negative rate (FNR) and limit of detection (LOD95 ) for recovering Bacillus spores using a macrofoam-swab sampling procedure. METHODS AND RESULTS: Bacillus anthracis Sterne or Bacillus atrophaeus Nakamura spores were deposited over a range of low target concentrations (2-500 per coupon) onto glass, stainless steel, vinyl tile and plastic. Samples were assayed using a modified Rapid Viability-PCR (mRV-PCR) method and the traditional plate culture method to obtain FNR and LOD95 results. CONCLUSIONS: Mean FNRs tended to be lower for mRV-PCR compared to culturing, and increased as spore concentration decreased for all surface materials. Surface material, but not B. anthracis surrogate, influenced FNRs with the mRV-PCR method. The mRV-PCR LOD95 was lowest for glass and highest for vinyl tile. LOD95 values overall were lower for mRV-PCR than for the culture method. SIGNIFICANCE AND IMPACT OF STUDY: This study adds to the limited data on FNR and LOD95 for mRV-PCR and culturing methods with low concentrations of B. anthracis sampled from various surface materials by the CDC macrofoam-swab method. These are key inputs for planning characterization and clearance studies for low contamination levels of B. anthracis.

The changing case-mix of hip fractures in Scotland - evidence from the Scottish Hip Fracture Audit.

Until discontinued in 2008, the Scottish Hip Fracture Audit collected and reported on data relating to the quality of care of hip fracture patients in Scotland. In 2013, the audit was recommenced under the umbrella of the MSK Audit group, which audits high volume orthopaedic pathways across Scotland. Our aim is to report on the changes in the demographics of hip fracture patients in Scotland between 2003 and 2013. There was an increase in the proportion of male patients from 2003 to 2013 (22.4% to 29.5%; p < 0.0001). An increased percentage of hip fracture patients were admitted from their own home (63.9% to 73.1%; p < 0.0001). Both these factors have deleterious effects on the outcome, and use of necessary resources, following hip fracture. There was also an increase in the percentage of patients who were American Society of Anesthesiologists Grade 3 (52.9% to 56.4%). Over the last decade, there has been a shift in the demographics of Scotland's hip fracture patients. If hip fracture incidence increases as predicted, this potentially more-challenging case-mix will likely impact on multiple health resources.

Proteomic signatures differentiating Bacillus anthracis Sterne sporulation on soil relative to laboratory media.

The process of sporulation is vital for the stability and infectious cycle of Bacillus anthracis. The spore is the infectious form of the organism and therefore relevant to biodefense. While the morphological and molecular events occurring during sporulation have been well studied, the influence of growth medium and temperature on the proteins expressed in sporulated cultures is not well understood. Understanding the features of B. anthracis sporulation specific to natural vs. laboratory production will address an important question in microbial forensics. In an effort to bridge this knowledge gap, a system for sporulation on two types of agar-immobilized soils was used for comparison to cultures sporulated on two common types of solid laboratory media, and one liquid sporulation medium. The total number of proteins identified as well as their identity differed between samples generated in each medium and growth temperature, demonstrating that sporulation environment significantly impacts the protein content of the spore. In addition, a subset of proteins common in all of the soil-cultivated samples was distinct from the expression profiles in laboratory medium (and vice versa). These differences included proteins involved in thiamine and phosphate metabolism in the sporulated cultures produced on soils with a notable increase in expression of ATP binding cassette (ABC) transporters annotated to be for phosphate and antimicrobial peptides. A distinct set of ABC transporters for amino acids, sugars and oligopeptides were found in cultures produced on laboratory media as well as increases in carbon and amino acid metabolism-related proteins. These protein expression changes indicate that the sporulation environment impacts the protein profiles in specific ways that are reflected in the metabolic and membrane transporter proteins present in sporulated cultures.

In situ synthesis of Au-shelled Ag nanoparticles on PDMS for flexible, long-life, and broad spectrum-sensitive SERS substrates.

A simple and fast one-step fabrication method of silver nanoparticles (AgNPs) on a polydimethylsiloxane (PDMS) film and their improvement as highly sensitive surface enhanced Raman scattering (SERS) substrates via atomically thin Au coatings is demonstrated. The thin Au layer provides oxidation resistivity while maintaining the broad spectral range SERS sensitivity of Ag nanoparticles.

Morphological variation, phylogenetic relationships, and geographic distribution of the Baenidae (Testudines), based on new specimens from the Uinta Formation (Uinta Basin), Utah (USA).

We described newly discovered baenid specimens from the Uintan North American Land Mammal Age (NALMA), in the Uinta Formation, Uinta Basin, Utah. These specimens include a partial skull and several previously undescribed postcranial elements of Baena arenosa, and numerous well-preserved shells of B. arenosa and Chisternon undatum. Baenids from the Uintan NALMA (46.5-40 Ma) are critical in that they provide valuable insight into the morphology and evolution of the diverse and speciose baenid family near the end of its extensive radiation, just prior to the disappearance of this clade from the fossil record. These Uintan specimens greatly increase the known variation in these late-surviving taxa and indicate that several characters thought to define these species should be reassessed. The partial cranium of B. arenosa, including portions of the basicranium, neurocranium, face, and lower jaw, was recently recovered from Uinta B sediments. While its morphology is consistent with known specimens of B. arenosa, we observed several distinct differences: a crescent-shaped condylus occipitalis that is concave dorsally, tuberculum basioccipitale that flare out laterally, and a distinct frontal-nasal suture. The current sample of plastral and carapacial morphology considerably expands the documented variation in the hypodigms of B. arenosa and C. undatum. Novel shell characters observed include sigmoidal extragular-humeral sulci, and small, subtriangular gular scutes. Subadult specimens reveal ontogenetic processes in both taxa, and demonstrate that diagnostic morphological differences between them were present from an early developmental age.

Genomic evaluation of age at first calving.

From their time of birth until their first lactation, dairy heifers incur management, health, and feed expenses while not producing milk. Much effort has been made to estimate optimal ages of first calving (AFC) for cows to reduce these costs, which can be as high as $2.50 per day, and ensure that animals are productive earlier in life. To identify AFC for 3 dairy cattle breeds (Holstein, Jersey, and Brown Swiss) that maximizes production, we retrieved phenotypic records for more than 14 million cows calving between 1997 and 2015 from the US national dairy database. The mean AFC for Holstein and Jersey has decreased by 2.4 and 2.7 mo, respectively, since 2006. When comparing the association of AFC with production and fertility traits, we found that decreased AFC was correlated with greater fertility and higher milk yield for all but the earliest group (18 to 20 mo). We also identified an unfavorable correlation of lower AFC with increasing stillbirth rates in Holstein (0.047 least squares means compared with a baseline of 24 mo) and Brown Swiss (0.062 least squares means). Finally, we identified favorable genetic correlations of lower AFC with lifetime net merit, heifer conception rate, cow conception rate, and daughter pregnancy rate in Holstein and Jersey cattle, and favorable correlations for net merit and heifer conception rate in Brown Swiss. To maximize lifetime production and reduce the effects of AFC on stillbirth, the AFC that maximizes production for Holstein and Brown Swiss is 21 to 22 mo, and for Jersey it is 20 to 21 mo. However, the effect of AFC on stillbirth reduces the benefits of calving at very young ages. Calculated genomic predicted transmitting ability for AFC showed an improvement in reliability of 20 percentage points in genomic young bulls compared with parent averages in Holstein, suggesting that genomic testing can improve selection for this trait.

A novel method for in situ synthesis of SERS-active gold nanostars on polydimethylsiloxane film.

A novel one-step in situ synthesis of gold nanostars (AuNSs) on a pre-cured polydimethylsiloxane (PDMS) film is proposed for the fabrication of highly sensitive surface-enhanced Raman scattering (SERS) substrates. Plasmonic activity of the substrates was investigated by collecting SERS maps of 4-mercaptobenzoic acid (4-MBA). The applicability of these flexible substrates is further demonstrated by SERS-based pesticide detection on fruit skin.

The burden of seasonal respiratory infections on a national telehealth service in England.

Seasonal respiratory illnesses present a major burden on primary care services. We assessed the burden of respiratory illness on a national telehealth system in England and investigated the potential for providing early warning of respiratory infection. We compared weekly laboratory reports for respiratory pathogens with telehealth calls (NHS 111) between week 40 in 2013 and week 29 in 2015. Multiple linear regression was used to identify which pathogens had a significant association with respiratory calls. Children aged <5 and 5-14 years, and adults over 65 years were modelled separately as were time lags of up to 4 weeks between calls and laboratory specimen dates. Associations with respiratory pathogens explained over 83% of the variation in cold/flu, cough and difficulty breathing calls. Based on the first two seasons available, the greatest burden was associated with respiratory syncytial virus (RSV) and influenza, with associations found in all age bands. The most sensitive signal for influenza was calls for 'cold/flu', whilst for RSV it was calls for cough. The best-fitting models showed calls increasing a week before laboratory specimen dates. Daily surveillance of these calls can provide early warning of seasonal rises in influenza and RSV, contributing to the national respiratory surveillance programme.

Health professionals' experiences of behavioural family therapy for adults with intellectual disabilities: a thematic analysis.

WHAT IS KNOWN ON THE SUBJECT?: Behavioural Family Therapy (BFT) has been shown to help people with some severe mental health conditions, such as schizophrenia, by reducing relapse rates and stress within families. It can be difficult to put family interventions, like BFT, into clinical practice. Families where someone has an intellectual disability can experience more stress compared to those who do not, but we know very little about using BFT with families where a member has an intellectual disability. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: We interviewed nine Community Learning Disability Nurses and Allied Health Professionals about their experiences delivering BFT to families where one member has an intellectual disability. We found that therapists' experiences of delivering BFT were broadly positive, although they found some aspects of their service frustrating. EXPLAIN THE IMPORTANCE OF THE PAPER'S FINDINGS FOR A NON-SPECIALIST AUDIENCE: The study identifies the perceived benefits of BFT as a model to work with families, where a member has an intellectual disability. The study highlights some of the challenges experienced by practitioners, notably issues with engagement and some issues specific to working with adults with an intellectual disability. The findings suggest that it needs to be clear which families would benefit most from BFT, that interventions need to be adapted for people with intellectual disabilities and that Community Learning Disability Nurses and Allied Health Professionals should have support from management to deliver these interventions. ABSTRACT: Introduction Studies have found family interventions (FIs) to be effective in reducing stress and relapse rates for a variety of mental health conditions. However, implementing FIs into clinical practice is challenging. Studies have suggested that levels of stress within some families of people with intellectual disabilities can be high. However, there is little reported about the use and implementation of FIs, such as Behavioural Family Therapy (BFT), in adult intellectual disability services. Purpose of study To explore the experiences of practitioners delivering BFT to adults with intellectual disabilities. Method A qualitative methodology was employed, using semi-structured individual interviews with BFT therapists from a health professional background (n = 9). Data were analysed thematically. Results Two overarching themes were identified: positivity and frustration. Discussion Implementation of therapy was identified as being broadly successful but with some underlying challenges, notably wider organizational issues and some issues specific to working with adults with intellectual disabilities. Implications for practice The broadly positive experiences reported provide encouragement for the delivery of FIs, such as BFT, to adults with intellectual disabilities, by professions outwith psychology. However, there is a need to provide clarity on referral processes, adapt materials accordingly for this client group and ensure that supportive management and supervision is available to therapists.

A Study of Hypermethylated Circulating Tumor DNA as a Universal Colorectal Cancer Biomarker.

BACKGROUND: Circulating tumor DNA (ctDNA) has emerged as a good candidate for tracking tumor dynamics in different cancer types, potentially avoiding repeated tumor biopsies. Many different genes can be mutated within a tumor, complicating procedures for tumor monitoring, even with highly sensitive next-generation sequencing (NGS) strategies. Droplet-based digital PCR (dPCR) is a highly sensitive and quantitative procedure, allowing detection of very low amounts of circulating tumor genetic material, but can be limited in the total number of target loci monitored. METHODS: We analyzed hypermethylation of 3 genes, by use of droplet-based dPCR in different stages of colorectal cancer (CRC), to identify universal markers for tumor follow-up. RESULTS: Hypermethylation of WIF1 (WNT inhibitory factor 1) and NPY (neuropeptide Y) genes was significantly higher in tumor tissue compared to normal tissue, independently of tumor stage. All tumor tissues appeared positive for one of the 2 markers. Methylated ctDNA (MetctDNA) was detected in 80% of metastatic CRC and 45% of localized CRC. For samples with detectable mutations in ctDNA, MetctDNA and mutant ctDNA (MutctDNA) fractions were correlated. During follow-up of different stage CRC patients, MetctDNA changes allowed monitoring of tumor evolution. CONCLUSIONS: These results indicate that MetctDNA could be used as a universal surrogate marker for tumor follow-up in CRC patients, and monitoring MetctDNA by droplet-based dPCR could avoid the need for monitoring mutations.