The Strategic Council for Research Excellence, Integrity, and Trust.

We announce the creation of a new body within the National Academies of Sciences, Engineering, and Medicine called the Strategic Council for Research Excellence, Integrity, and Trust, charged with advancing the overall health, quality, and effectiveness of the research enterprise across all domains that fund, execute, disseminate, and apply scientific work in the public interest. By promoting the alignment of incentives and policies, adoption of standard tools, and implementation of proven methods, the Strategic Council seeks to optimize the excellence and trustworthiness of research for the benefit of society.

Psychosocial determinants of colorectal Cancer screening uptake among African-American men: understanding the role of masculine role norms, medical mistrust, and normative support.

OBJECTIVES: Despite having the highest colorectal cancer (CRC) incidence and mortality across all major racial/ethnic groups, African-American men consistently have poor CRC screening rates. Gendered and racialized beliefs and norms have been associated with African-American men's lower medical assistance-seeking rates, but how these notions influence African-American men's CRC screening practices merits further investigation. The purpose of this study was to examine the influence of psychosocial determinants of men's health on CRC screening uptake among African-American men in three states. DESIGN: Participants were recruited via CuttingCRC.com and through culturally-tailored flyers, newspaper ads, and snowball sampling, among other methods. From April 2019-August 2019, 11 focus groups were conducted with English-speaking Black/African-American men who (a) were between ages 45-75, (b) were born in the United States, (c) had a working telephone, and (d) lived in Minnesota, Ohio, or Utah. Multiple-cycle coding, Hatch's 9-step approach, and constant comparative data analysis was employed for de-identified transcript data. RESULTS: Eighty-four African-American men met inclusion criteria and participated. Their mean age was 59.34 ± 7.43. In regards to CRC screening status, Ohio had the most previously screened participants (85%), followed by Minnesota (84%) and Utah (76%). Two major CRC screening barriers (masculine role norms and medical mistrust) - both encompassed 3-5 subthemes, and one major facilitator (normative support from family members or social networks) emerged. CONCLUSIONS: Despite CRC screening's life-saving potential, African-American men have had the lowest 5-year relative survival for more than 40 years. When developing interventions and health promotion programs aiming to eliminate the racial disparity in CRC outcomes, addressing both masculine role norms and medical mistrust barriers to CRC screening completion among African-American men is warranted.

Effect of dry-off management on milking behavior, milk yield, and somatic cell count of dairy cows milked in automated milking systems.

Milk production may be reduced before dry-off to decrease the risk of cows developing intramammary infections during the dry period. Such reductions in milk may be possible in automated milking systems (AMS) where milking frequency and feed allocation at the AMS can be controlled at the cow level. This study investigated the effect of dry-off management of cows milked in AMS on milk yield, milking behavior, and somatic cell count (SCC). Using a 2 × 2 factorial arrangement of treatments, applied from d 14 to 1 before dry-off, 445 cows from 5 commercial dairy farms in Quebec, Canada, were assigned within farm to either (1) reduced feed [RF; allowed a maximum of 0.75 kg/d of AMS pellet for the first week (14 to 8 d before dry-off) of treatment, and 0.50 kg/d for the second week (7 to 1 d before dry-off) of treatment], or (2) nonreduced feed (NF; allowed up to 2 kg/d of AMS pellet), and either (1) reduced milking (RM; reduced to 2 milkings/d or as many times as required to yield 17 kg/milking), or (2) nonreduced milking (NM; allowed up to 6 AMS milkings/d) and no maximum production. Feed and milking behavior data, as well as milk yield and SCC were collected from the AMS software. The RF cows had lower AMS feed delivered during the treatment period, as per the experimental design. Across the treatment period, the NF-NM cows had the highest milking frequency (2.7 times/d), followed by the RF-NM cows (2.4 times/d), and then both of the RM groups (1.8 times/d), which did not differ from each other. All cows, except the NF-NM cows, were gradually milked less frequently as dry-off approached. Across the entire 2-wk treatment period before dry-off, cows with RM allowance experienced a higher reduction in milk yield compared with the cows with no milking allowance restrictions (-4.8 vs. -3.6 kg). Similarly, cows with a RF allocation tended to have a higher reduction in milk yield than cows with NF (-4.6 vs. -3.7 kg). As result, those cows with both reduced milking permissions and feed allocation at the AMS experienced the greatest drop in milk production before dry-off. There were no differences between treatments for milking frequency or yield in the next lactation. Somatic cell score (calculated from SCC) was not different between treatments in the 2-wk or day before dry-off, nor in the first month after calving. Overall, these data suggest that reducing both milking frequency and feed quantity in the AMS is the most efficient method to decrease milk yield before dry-off, without negatively influencing milking frequency or yield in the next lactation, as well as without affecting milk quality.

Endophytic Microorganisms Associated with Reversion of Silverleaf Disease Symptoms in Apple.

Silverleaf is caused by the fungus Chondrostereum purpureum, which produces wood necrosis and foliar silvering in woody plants. Field observations and studies in apple have shown the reversion of foliar symptoms. Because plants were clones and received identical agronomical management, it was hypothesized that reversion is driven by endophytic microbiota. Thus, the objectives of this study were to compare healthy, diseased, and reverted plants with respect to their physiology, endophytic microbial communities, antagonistic ability of their endophytes against C. purpureum, and defense genes expression. Water potential, stomatal conductance, chlorophyll content, and fluorescence were measured. Endophytic bacterial and fungal DNA were analyzed by denaturing gradient gel electrophoresis, and community richness and similarity were calculated. Wood cores were collected and bacterial and fungal endophytes were isolated and confronted with C. purpureum-virulent strains in dual-culture assays. Defense genes expression was measured by quantitative PCR. Results indicated that there were no differences in physiological parameters between healthy and reverted plants, except for fluorescence, and both type of plants differed from diseased ones. Bacterial and fungal community richness was similar in healthy and reverted plants and higher than in diseased ones. Endophytes from reverted and healthy plants showed high antagonism to C. purpureum. Furthermore, nonexpressor of pathogenesis-related gene 1 expression was upregulated in reverted plants, whereas phenylalanine ammonia lyase and polygalacturonase-inhibiting protein genes showed higher values in diseased plants. Overall, physiological, molecular, and microbial characteristics were similar between healthy and reverted plants, and both differed from diseased ones. Therefore, reversion of symptoms is associated with changes in the endophytic microbiota, which seems to be a promising source of biological control agents against C. purpureum.

Diverse caregivers' HPV vaccine-related awareness and knowledge.

Objectives: To assess factors associated with HPV vaccine-related awareness and knowledge among caregivers of adolescents from five ethnic community groups in Utah.Design: For this community-based participatory research study, we surveyed N = 228 caregivers of teens aged 11-17 years from African American, African refugee, American Indian/Alaskan Native, Hispanic/Latino, and Native Hawaiian/Pacific Islander community groups in Utah about their HPV vaccine awareness and knowledge.Results: Participants exhibited high awareness of cervical cancer (71.05%), moderate awareness of HPV (53.95%), and low awareness of the HPV vaccine (46.49%). HPV vaccine-related knowledge was mostly worse, with fewer than half the participants reporting knowing that HPV can cause cervical cancer (46.93%), that most people are infected with HPV at some point in their lives (28.95%), that HPV is asymptomatic in females (36.40%) and males (37.28%), that the HPV vaccine is recommended for adolescent females (41.67%) and males (36.40%), and that the HPV vaccine requires more than one dose (27.19%). HPV vaccine-related awareness and knowledge were significantly associated with race/ethnicity, educational attainment, income, occupation, birthplace, parents' birthplace, English usage, health insurance coverage, type of health insurance, and child having a primary care provider (all p < 0.05). HPV vaccine-related knowledge (p < 0.05) and awareness (p < 0.05) of caregivers were associated with a child in the household receiving the HPV vaccine.Conclusion: Our findings indicate a need to develop educational interventions in collaboration with diverse communities in Utah. We underscore the importance of promoting knowledge about the existence of the HPV vaccine, as well as deeper HPV vaccine-related issues (e.g. HPV risks, treatment, and recommendations).

A PCR-Based Method for the Rapid Detection of Chondrostereum purpureum in Apple.

Silverleaf caused by the basidiomycete Chondrostereum purpureum affects numerous woody species, including fruit tree crops like apple, resulting in wood necrosis and foliar silvering. There are no curative alternatives for this disease, and its management is by prevention methods. Therefore, the aim of this study was to develop a rapid diagnostic tool for the detection and identification of C. purpureum directly from woody tissues to help distinguish the pathogen from other basidiomycetes that are commonly found on apple. The silverleaf pathogen was isolated from different hosts and locations, and Koch's postulates were performed by inoculating the isolates on apple cuttings and measuring internal necrosis. A previously described APN 1 pair of primers specificity was also tested against 25 C. purpureum isolates in this study, using other wood rotting species as negative controls. Seven virulent isolates were inoculated on apple cuttings, and DNA was extracted from the cuttings' sawdust and amplified using APN 1, after 22 days of incubation. To prove the efficiency of the method in the field, DNA from healthy nursery plants inoculated with two virulent isolates, and naturally infected plants showing different levels of foliar symptoms, were tested. Presence of the fungus was verified by reisolation on APDA in all assays. Koch's postulates indicated that all C. purpureum isolates were pathogenic, showing different virulence levels, and APN 1 primers were able to discriminate them from other basidiomycetes. The method was also able to detect C. purpureum from artificially inoculated plants as well as naturally infected ones, demonstrating that the protocol may become a rapid minimally destructive diagnostic tool to detect the pathogen without the need to isolate it from tissues, and thus taking measures to prevent its dissemination.

Microscopy-based high-throughput assays enable multi-parametric analysis to assess adverse effects of nanomaterials in various cell lines.

Manufactured nanomaterials (MNMs) selected from a library of over 120 different MNMs with varied compositions, sizes, and surface coatings were tested by four different laboratories for toxicity by high-throughput/-content (HT/C) techniques. The selected particles comprise 14 MNMs composed of CeO2, Ag, TiO2, ZnO and SiO2 with different coatings and surface characteristics at varying concentrations. The MNMs were tested in different mammalian cell lines at concentrations between 0.5 and 250 µg/mL to link physical-chemical properties to multiple adverse effects. The cell lines are derived from relevant organs such as liver, lung, colon and the immune system. Endpoints such as viable cell count, cell membrane permeability, apoptotic cell death, mitochondrial membrane potential, lysosomal acidification and steatosis have been studied. Soluble MNMs, Ag and ZnO, were toxic in all cell types. TiO2 and SiO2 MNMs also triggered toxicity in some, but not all, cell types and the cell type-specific effects were influenced by the specific coating and surface modification. CeO2 MNMs were nearly ineffective in our test systems. Differentiated liver cells appear to be most sensitive to MNMs, Whereas most of the investigated MNMs showed no acute toxicity, it became clear that some show adverse effects dependent on the assay and cell line. Hence, it is advised that future nanosafety studies utilise a multi-parametric approach such as HT/C screening to avoid missing signs of toxicity. Furthermore, some of the cell type-specific effects should be followed up in more detail and might also provide an incentive to address potential adverse effects in vivo in the relevant organ.

Diverse Families' Experiences with HPV Vaccine Information Sources: A Community-Based Participatory Approach.

Current sources of publicly available human papillomavirus (HPV) information may not adequately meet the needs of diverse families. This study sought to describe associations between sociodemographic and acculturation factors, and sources of HPV information among diverse parents and caregivers. Community organizations purposively recruited participants from African American, African refugee, Hispanic/Latino, American Indian, and Native Hawaiian and Pacific Islander communities for a 21-item survey (N = 228). Ninenty-three of these participants also participated in ten focus groups conducted in three languages. Descriptive statistics and Fishers' Exact Test for Count Data were produced and triangulated with focus group data to provide additional context. Overall, HPV vaccine awareness and knowledge in the five communities was low. This study found that a greater proportion of lower-acculturated participants had heard of HPV through personal networks (foreign-born = 50 % vs US-born = 30 %, p < 0.05; medium acculturation = 60 % vs high acculturation = 26 %, p = 0.01), while greater proportions of US-born participants reported media sources (49 % vs foreign-born = 29 %, p < 0.05). Across communities, healthcare system sources were described as important and preferred sources of HPV information. Hearing about the HPV vaccine from healthcare settings was significantly associated with increased accuracy in HPV vaccine knowledge (p < 0.05). Communities described a need for more in-depth information about the HPV vaccine, and culturally and linguistically appropriate educational materials. Culturally-competent delivery of HPV information through the healthcare system sources may be important in improving knowledge and acceptability of the HPV vaccine among diverse families.

Outcomes of Patients Treated in the UK Proton Overseas Programme: Non-central Nervous System Group.

AIMS: The UK Proton Overseas Programme (POP) was launched in 2008. The Proton Clinical Outcomes Unit (PCOU) warehouses a centralised registry for collection, curation and analysis of all outcomes data for all National Health Service-funded UK patients referred and treated abroad with proton beam therapy (PBT) via the POP. Outcomes are reported and analysed here for patients diagnosed with non-central nervous system tumours treated from 2008 to September 2020 via the POP. MATERIALS AND METHODS: All non-central nervous system tumour files for treatments as of 30 September 2020 were interrogated for follow-up information, and type (following CTCAE v4) and time of onset of any late (>90 days post-PBT completion) grade 3-5 toxicities. RESULTS: Four hundred and ninety-five patients were analysed. The median follow-up was 2.1 years (0-9.3 years). The median age was 11 years (0-69 years). 70.3% of patients were paediatric (<16 years). Rhabdomyosarcoma (RMS) and Ewing sarcoma were the most common diagnoses (42.6% and 34.1%). 51.3% of treated patients were for head and neck (H&N) tumours. At last known follow-up, 86.1% of all patients were alive, with a 2-year survival rate of 88.3% and 2-year local control of 90.3%. Mortality and local control were worse for adults (≥25 years) than for the younger groups. The grade 3 toxicity rate was 12.6%, with a median onset of 2.3 years. Most were in the H&N region in paediatric patients with RMS. Cataracts (30.5%) were the most common, then musculoskeletal deformity (10.1%) and premature menopause (10.1%). Three paediatric patients (1-3 years at treatment) experienced secondary malignancy. Seven grade 4 toxicities occurred (1.6%), all in the H&N region and most in paediatric patients with RMS. Six related to eyes (cataracts, retinopathy, scleral disorder) or ears (hearing impairment). CONCLUSIONS: This study is the largest to date for RMS and Ewing sarcoma, undergoing multimodality therapy including PBT. It demonstrates good local control, survival and acceptable toxicity rates.

Assessing Equity of Access to Proton Beam Therapy: A Literature Review.

Proton beam therapy (PBT) is one of the most advanced radiotherapy technologies, with growing evidence to support its use in specific clinical scenarios and exponential growth of demand and capacity worldwide over the past few decades. However, geographical inequalities persist in the distribution of PBT centres, which translate into variations in access and use of this technology. The aim of this work was to look at the factors that contribute to these inequalities, to help raise awareness among stakeholders, governments and policy makers. A literature search was conducted using the Population, Intervention, Comparison, Outcomes (PICO) criteria. The same search strategy was run in Embase and Medline and identified 242 records, which were screened for manual review. Of these, 24 were deemed relevant and were included in this analysis. Most of the 24 publications included in this review originated from the USA (22/24) and involved paediatric patients, teenagers and young adults (61% for children and/or teenagers and young adults versus 39% for adults). The most reported indicator of disparity was socioeconomic status (16/24), followed by geographical location (13/24). All the studies evaluated in this review showed disparities in the access to PBT. As paediatric patients make up a significant proportion of the PBT-eligible patients, equity of access to PBT also raises ethical considerations. Therefore, further research is needed into the equity of access to PBT to reduce the care gap.

Outcomes of Patients Treated in the UK Proton Overseas Programme: Central Nervous System Group.

AIMS: In 2008, the UK National Health Service started the Proton Overseas Programme (POP), to provide access for proton beam therapy (PBT) abroad for selected tumour diagnoses while two national centres were being planned. The clinical outcomes for the patient group treated for central nervous system (CNS), base of skull, spinal and paraspinal malignancies are reported here. MATERIALS AND METHODS: Since the start of the POP, an agreement between the National Health Service and UK referring centres ensured outcomes data collection, including overall survival, local tumour control and late toxicity data. Clinical and treatment-related data were extracted from this national patient database. Grade ≥3 late toxicities were reported following Common Terminology Criteria for Adverse Events (CTCAE) v 4.0 definition, occurring later than 90 days since the completion of treatment. RESULTS: Between 2008 and September 2020, 830 patients were treated within the POP for the above listed malignancies. Overall survival data were available for 815 patients and local control data for 726 patients. Toxicity analysis was carried out on 702 patients, with patients excluded due to short follow-up (<90 days) and/or inadequate toxicity data available. After a median follow-up of 3.34 years (0.06-11.58), the overall survival was 91.2%. The local control rate was 85.9% after a median follow-up of 2.81 years (range 0.04-11.58). The overall grade ≥3 late toxicity incidence was 11.97%, after a median follow-up of 1.72 years (0.04-8.45). The median radiotherapy prescription dose was 54 GyRBE (34.8-79.2). CONCLUSIONS: The results of this study indicate the safety of PBT for CNS tumours. Preliminary clinical outcomes following PBT for paediatric/teen and young adult and adult CNS tumours treated within the POP are encouraging, which reflects accurate patient selection and treatment quality. The rate of late effects compares favourably with published cohorts. Clinical outcomes from this patient cohort will be compared with those of UK-treated patients since the start of the national PBT service in 2018.

First Report of Root Rot of Chicory Caused by Phytophthora cryptogea in Chile.

Chicory (Cichorium intybus L. var sativum Bisch.), a relatively new high-value crop in Chile, was introduced for commercial production of inulin. Inulins are polysaccharides extracted from chicory tap roots that are used in processed foods because of their beneficial gastrointestinal properties. Approximately 3,000 ha of chicory are grown for local processing in the BioBio Region near Chillan in south central Chile. Recently, a severe rot of 1 to 3% of mature roots in the field and after harvest has been observed in most fields, which caused yield and quality losses. Typical symptoms include a brown discoloration and a soft, watery decay of the root. Tissue pieces from symptomatic roots were placed on water agar and clarified V8 juice agar medium amended with antibiotics (1) for isolation of the causal pathogen. A Phytopthora sp. had been consistently isolated from root lesions, and axenic cultures were obtained using single-hypha transfers. The species was provisionally identified as Phytopthora cryptogea (Pethybridge and Lafferty, 1919) on the basis of morphological and cultural characteristics (1). Mycelia grew between 5 and 30°C with optimal growth at 20 to 25°C and no growth at 35°C. All isolates produced hyphal swellings and nonpapillate, persistent, internally proliferating, and ovoid to obpyriform sporangia with mean dimensions of 45 × 31 µm in sterile soil extract. The isolates were of A1 mating type because they produced oospores only when paired with reference isolates of P. cinnamomi A2 on clarified V8 juice agar amended with thiamine, tryptophan, and ß-sitosterol (1) after 20 days at 20°C in the dark. On the basis of morphological and sequence data from cytochrome c oxidase subunit 1 and 2, internal transcribed spacer 2, and ß-tubulin (GenBank Accession Nos. JQ037796 to JQ037798, respectively), the pathogen was identified as P. cryptogea. Pathogenicity tests were conducted using three isolates of P. cryptogea by placing a 7-mm-diameter disk from a 1-week-old V8 agar culture on 10 wounded and nonwounded healthy chicory roots (2). Control roots were mock inoculated with agar plugs. The inoculated roots were incubated at 20°C in a moist chamber. Root rot symptoms, identical to those observed both in field and storage, developed after 4 to 6 days only on wounded sites inoculated with the pathogen, and P. cryptogea was reisolated from these inoculated plants. Mock-inoculated roots remained healthy. This experiment was completed twice and similar results were obtained. To our knowledge, this is the first report of Phytophthora root rot of chicory caused by P. cryptogea in Chile. References: (1) D. C. Erwin and O. K. Ribeiro. Phytophthora Diseases Worldwide. The American Phytopathological Society, St. Paul, MN, 1996. (2) M. E. Stanghellini and W. C. Kronland. Plant Dis. 66:262, 1982.

New goals for science philanthropy.

Science philanthropy is experiencing a growth spurt, propelled by the newly acquired wealth of individuals and foundations, as well as a desire to address challenges such as infectious disease, fire, drought, and food and water security. Especially in the United States, this is altering the dynamics of the research ecosystem, which has been dominated by government funding since the end of World War II. This change comes with new perspectives and approaches to solving the world's problems. And it comes with a commitment to increase equity in funding.

Normal Tissue Complication Probability Modelling for Toxicity Prediction and Patient Selection in Proton Beam Therapy to the Central Nervous System: A Literature Review.

Normal tissue complication probability (NTCP) models can guide clinical decision making in radiotherapy. In recent years, they have been used for patient selection for proton beam therapy (PBT) for some anatomical tumour sites. This review synthesizes the published evidence regarding the use of NTCP models to predict the toxicity of PBT, for different end points in patients with brain tumours. A search of Medline and Embase using the Patients, Intervention, Comparison, Outcome (PICO) criteria was undertaken. In total, 37 articles were deemed relevant and were reviewed in detail. Nineteen articles on NTCP modelling of toxicity end points were included. Of these, 11 were comparative NTCP studies of PBT versus conventional photon radiotherapy (XRT), which evaluated differences in plan dosimetry and then assumed that XRT-derived literature estimates of NTCP would be applicable to both. Seven papers derived NTCP models based on PBT outcome data, two of which provided model parameters. Among analysed end points, the reduced risk of secondary tumours with PBT as compared with XRT is estimated - through modelling studies - to be considerable and was highlighted by most authors. For other analysed end points, the clinical benefit of PBT mainly depends on tumour location in relation to organs at risk as well as prescription doses. NTCP models can be useful tools for treatment plan comparison. However, most published toxicity data were derived from XRT cohorts; this review has highlighted the need for further studies relating dose-volume parameters to observed toxicity in PBT-treated patients. Specifically, there is a need for PBT-specific NTCP models that can be implemented in the clinical practice. NTCP models built on robust clinical data for the most common radiotherapy toxicities in the brain would potentially redefine the current indications for PBT.

Heterorhabditis atacamensis n. sp. (Nematoda: Heterorhabditidae), a new entomopathogenic nematode from the Atacama Desert, Chile.

A new Heterorhabditis species of entomopathogenic nematode was isolated from soil of the Atacama Desert in Chile. The new species is characterized by morphometrics of the infective juvenile (IJ) with length (L) = 611 (578-666) µm, head to excretory pore length (EP) = 115 (101-126) µm, tail = 69 (62-79) µm long, (EP/tail) × 100 (E%) = 165 (149-182) and L/maximum body diameter (ratio a) = 28 (25-31). The male has spicules 45 (40-49) µm long, gubernaculum 20 (17-22) µm long and (spicule length/anal body diameter) × 100 (SW%) = 205 (179-249). The hermaphroditic adult has shallow cuticular folds immediately anterior and posterior to the vulva, a slight post-anal swelling and a finely rounded tail terminus. Morphologically, H. atacamensis n. sp. resembles H. safricana, H. marelatus, H. downesi and H. amazonensis, but can be distinguished by characters of adult and IJ stages. In particular, for adult males, H. atacamensis n. sp. differs from H. amazonensis by the number and orientation of the genital papillae and from H. downesi by the position of the excretory pore; by the shape of the female tail terminus from H. downesi and by the position of the IJ hemizonid from H. marelatus. Heterorhabditis atacamensis n. sp. is further characterized by internal transcribed spacer (ITS) and D2D3 rDNA sequences, the closest species, H. safricana, being separated by 13 bp across 730 bp of the ITS (incorporating ITS1 (partial sequence), 5.8S (complete sequence), ITS2 (complete sequence)) and 5 bp across 592 bp of the partial 28S (incorporating D2D3) sequence. The morphological and molecular data confirm that H. atacamensis n. sp. is a valid species.

A Predictive Model for Reactive Tube Feeding in Head and Neck Cancer Patients Undergoing Definitive (Chemo) Radiotherapy.

AIMS: Careful management of a patient's nutritional status during and after treatment for head and neck squamous cell cancers (HNSCC) is crucial for optimal outcomes. The aim of this study was to develop a model for stratifying a patient's risk of requiring reactive enteral feeding through a nasogastric tube during radiotherapy for HNSCC, based on clinical and treatment-related factors. MATERIALS AND METHODS: A cohort of consecutive patients treated with definitive (chemo)radiotherapy for HNSCC between January 2016 and January 2018 was identified in the institutional electronic database for retrospective analysis. Patients requiring enteral feeding pretreatment were excluded. Clinical and treatment data were obtained from prospectively recorded electronic clinical notes and planning software. RESULTS: Baseline patient characteristics and tumour-related parameters were captured for 225 patients. Based on the results of the univariate analysis and using a stepwise backwards selection process, clinical and dosimetric variables were selected to optimise a clinically predictive multivariate model, fitted using logistic regression. The parameters found to affect the probability, P, of requiring a nasogastric feeding tube for >4 weeks in our clinical multivariate model were: tumour site, tumour stage (early T0/1/2 stage versus advanced T3/T4 stage), chemotherapy drug (none versus any drug) and mean dose to the contralateral parotid gland. A scoring model using the regression coefficients of the selected variables in the clinical multivariate model achieved an area under the curve (AUC) of 0.745 (95% confidence interval 0.678-0.812), indicating good discriminative performance. Internal validation of the model involved splitting the dataset 80:20 into training and test datasets 10 times and assessing differences in AUC of the model fitted to these. CONCLUSIONS: We developed an easy-to-use prediction model based on both clinical and dosimetric parameters, which, once externally validated, can lead to more personalised treatment planning and inform clinical decision-making on the appropriateness of prophylactic versus reactive enteral feeding.

Sex without crossing over in the yeast Saccharomycodes ludwigii.

BACKGROUND: Intermixing of genomes through meiotic reassortment and recombination of homologous chromosomes is a unifying theme of sexual reproduction in eukaryotic organisms and is considered crucial for their adaptive evolution. Previous studies of the budding yeast species Saccharomycodes ludwigii suggested that meiotic crossing over might be absent from its sexual life cycle, which is predominated by fertilization within the meiotic tetrad. RESULTS: We demonstrate that recombination is extremely suppressed during meiosis in Sd. ludwigii. DNA double-strand break formation by the conserved transesterase Spo11, processing and repair involving interhomolog interactions are required for normal meiosis but do not lead to crossing over. Although the species has retained an intact meiotic gene repertoire, genetic and population analyses suggest the exceptionally rare occurrence of meiotic crossovers in its genome. A strong AT bias of spontaneous mutations and the absence of recombination are likely responsible for its unusually low genomic GC level. CONCLUSIONS: Sd. ludwigii has followed a unique evolutionary trajectory that possibly derives fitness benefits from the combination of frequent mating between products of the same meiotic event with the extreme suppression of meiotic recombination. This life style ensures preservation of heterozygosity throughout its genome and may enable the species to adapt to its environment and survive with only minimal levels of rare meiotic recombination. We propose Sd. ludwigii as an excellent natural forum for the study of genome evolution and recombination rates.

Surface Chemistry-Dependent Evolution of the Nanomaterial Corona on TiO2 Nanomaterials Following Uptake and Sub-Cellular Localization.

Nanomaterial (NM) surface chemistry has an established and significant effect on interactions at the nano-bio interface, with important toxicological consequences for manufactured NMs, as well as potent effects on the pharmacokinetics and efficacy of nano-therapies. In this work, the effects of different surface modifications (PVP, Dispex AA4040, and Pluronic F127) on the uptake, cellular distribution, and degradation of titanium dioxide NMs (TiO2 NMs, ~10 nm core size) are assessed and correlated with the localization of fluorescently-labeled serum proteins forming their coronas. Imaging approaches with an increasing spatial resolution, including automated high throughput live cell imaging, correlative confocal fluorescence and reflectance microscopy, and dSTORM super-resolution microscopy, are used to explore the cellular fate of these NMs and their associated serum proteins. Uncoated TiO2 NMs demonstrate a rapid loss of corona proteins, while surface coating results in the retention of the corona signal after internalization for at least 24 h (varying with coating composition). Imaging with two-color super-resolution dSTORM revealed that the apparent TiO2 NM single agglomerates observed in diffraction-limited confocal microscopy are actually adjacent smaller agglomerates, and provides novel insights into the spatial arrangement of the initial and exchanged coronas adsorbed at the NM surfaces.