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1.
Appl Radiat Isot ; 205: 111171, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38181577

RESUMO

Absolute gamma-ray emission intensities for 36 characteristic gamma rays from the decay of 224Ra, 212Pb, and their progeny were determined by measuring sources calibrated for activity by means of primary methods based on well-defined high-purity germanium (HPGe) detectors at both NIST and NPL. Results from the two laboratories agree with recent data evaluations, except for gamma rays with low emission intensities. The decay schemes have been re-balanced based on the new results. In addition, the half-life for 212Pb was measured using several HPGe detectors, ionization chambers, and a well-type NaI(Tl) detector.

2.
J Dairy Sci ; 107(1): 383-397, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37709046

RESUMO

Enteric methane (CH4) emissions of 3 genetic groups (GG) of dairy cows were recorded across the grazing season (early March to late October). The 3 GG were (1) high economic breeding index (EBI) Holstein-Friesian (HF) representative of the top 1% of dairy cows in Ireland at the time of the study (elite), (2) national average (NA) EBI, which were representative of the average HF dairy cow in Ireland, and (3) purebred Jersey (JE) cows. Enteric CH4 was recorded using GreenFeed technology. Seasonal variation in CH4 was observed, with the lowest daily CH4 emissions and CH4 expressed per unit of dry matter intake occurring in spring (253 g/d and 15.56 g/kg, respectively), intermediate in summer (303 g/d and 18.26 g/kg, respectively), and greatest in autumn (324 g/d and 19.80 g/kg, respectively). Seasonal variation was also observed in the proportion of gross energy intake converted to CH4 (Ym); in the spring the Ym was lowest at 0.046, increasing to 0.053 and 0.058 in the summer and autumn, respectively. There was no difference in daily CH4 between the elite and NA, whereas JE had lower CH4 emissions compared with the elite. When expressed per unit of milk solids (fat + protein yield; MS), the elite and JE produced 6.8% and 9.7% less CH4 per kilogram of MS, respectively, compared with NA. There was no difference between the GG for CH4 per unit of DMI or the Ym. This research emphasizes the variation in CH4 emissions across the grazing season and among cows of differing genetic merit for CH4 emission intensities but not for CH4 per unit of DMI or the Ym.


Assuntos
Lactação , Leite , Feminino , Bovinos , Animais , Leite/metabolismo , Lactação/genética , Dieta/veterinária , Metano/metabolismo , Ingestão de Energia
4.
QJM ; 116(8): 659-666, 2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37220898

RESUMO

BACKGROUND: The Coronavirus pandemic (COVID-19) curtailed endoscopy services, adding to diagnostic backlogs. Building on trial evidence for a non-endoscopic oesophageal cell collection device coupled with biomarkers (Cytosponge), an implementation pilot was launched for patients on waiting lists for reflux and Barrett's oesophagus surveillance. AIMS: (i) To review reflux referral patterns and Barrett's surveillance practices. (ii) To evaluate the range of Cytosponge findings and impact on endoscopy services. DESIGN AND METHODS: Cytosponge data from centralized laboratory processing (trefoil factor 3 (TFF3) for intestinal metaplasia (IM), haematoxylin & eosin for cellular atypia and p53 for dysplasia) over a 2-year period were included. RESULTS: A total of 10 577 procedures were performed in 61 hospitals in England and Scotland, of which 92.5% (N = 9784/10 577) were sufficient for analysis. In the reflux cohort (N = 4074 with gastro-oesophageal junction sampling), 14.7% had one or more positive biomarkers (TFF3: 13.6% (N = 550/4056), p53: 0.5% (21/3974), atypia: 1.5% (N = 63/4071)), requiring endoscopy. Among samples from individuals undergoing Barrett's surveillance (N = 5710 with sufficient gland groups), TFF3-positivity increased with segment length (odds ratio = 1.37 per cm (95% confidence interval: 1.33-1.41, P < 0.001)). Some surveillance referrals (21.5%, N = 1175/5471) had ≤1 cm segment length, of which 65.9% (707/1073) were TFF3 negative. Of all surveillance procedures, 8.3% had dysplastic biomarkers (4.0% (N = 225/5630) for p53 and 7.6% (N = 430/5694) for atypia), increasing to 11.8% (N = 420/3552) in TFF3+ cases with confirmed IM and 19.7% (N = 58/294) in ultra-long segments. CONCLUSIONS: Cytosponge-biomarker tests enabled targeting of endoscopy services to higher-risk individuals, whereas those with TFF3 negative ultra-short segments could be reconsidered regarding their Barrett's oesophagus status and surveillance requirements. Long-term follow-up will be important in these cohorts.


Assuntos
Esôfago de Barrett , COVID-19 , Neoplasias Esofágicas , Humanos , Esôfago de Barrett/diagnóstico , Triagem , Proteína Supressora de Tumor p53 , Endoscopia , Biomarcadores/análise , Neoplasias Esofágicas/diagnóstico
5.
NPJ Biofilms Microbiomes ; 8(1): 36, 2022 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-35508464

RESUMO

It is difficult to disentangle the many variables (e.g. internal or external cues and random events) that shape the microbiota in the gastrointestinal tract of any living species. Ecological assembly processes applied to microbial communities can elucidate these drivers. In our study, farmed Atlantic cod (Gadus morhua) were fed a diet of 10% macroalgae supplement (Ulva rigida [ULVA] or Ascophyllum nodosum [ASCO] or a non-supplemented control diet [CTRL]) over 12 weeks. We determined the influence of ecological assembly processes using a suite of null-modelling tools. We observed dissimilarity in the abundance of common OTUs over time, which was driven by deterministic assembly. The CTRL samples showed selection as a critical assembly process. While dispersal limitation was a driver of the gut microbiome for fish fed the macroalgae supplemented diet at Week 12 (i.e., ASCO and ULVA). Fish from the ASCO grouping diverged into ASCO_N (normal) and ASCO_LG (lower growth), where ASCO_LG individuals found the diet unpalatable. The recruitment of new taxa overtime was altered in the ASCO_LG fish, with the gut microbiome showing phylogenetic underdispersion (nepotistic species recruitment). Finally, the gut microbiome (CTRL and ULVA) showed increasing robustness to taxonomic disturbance over time and lower functional redundancy. This study advances our understanding of the ecological assembly and succession in the hindgut of juvenile Atlantic cod across dietary treatments. Understanding the processes driving ecological assembly in the gut microbiome, in fish research specifically, could allow us to manipulate the microbiome for improved health or resilience to disease for improved aquaculture welfare and production.


Assuntos
Gadus morhua , Microbioma Gastrointestinal , Animais , Dieta/veterinária , Suplementos Nutricionais , Filogenia
6.
Nat Commun ; 13(1): 1407, 2022 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-35301290

RESUMO

Barrett's esophagus is a pre-malignant lesion that can progress to esophageal adenocarcinoma. We perform a multi-omic analysis of pre-cancer samples from 146 patients with a range of outcomes, comprising 642 person years of follow-up. Whole genome sequencing reveals complex structural variants and LINE-1 retrotransposons, as well as known copy number changes, occurring even prior to dysplasia. The structural variant burden captures the most variance across the cohort and genomic profiles do not always match consensus clinical pathology dysplasia grades. Increasing structural variant burden is associated with: high levels of chromothripsis and breakage-fusion-bridge events; increased expression of genes related to cell cycle checkpoint, DNA repair and chromosomal instability; and epigenetic silencing of Wnt signalling and cell cycle genes. Timing analysis reveals molecular events triggering genomic instability with more clonal expansion in dysplastic samples. Overall genomic complexity occurs early in the Barrett's natural history and may inform the potential for cancer beyond the clinically discernible phenotype.


Assuntos
Esôfago de Barrett , Neoplasias Esofágicas , Esôfago de Barrett/genética , Esôfago de Barrett/patologia , Estudos de Coortes , Estudos Transversais , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Humanos , Retroelementos/genética
7.
Occup Med (Lond) ; 72(4): 260-263, 2022 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-35233606

RESUMO

BACKGROUND: There has been increasing evidence that physicians in gynaecology are not routinely enquiring about work during consultations. AIMS: To explore the effect gynaecological conditions can have on work functioning, the importance of work outcomes among patients and whether work considerations are discussed during clinical consultations. METHODS: A cross-sectional survey was administered to employed patients attending a gynaecological clinic at Guy's Hospital. The survey assessed four areas: demographics, gynaecological condition (including self-assessed severity), work status and perceived impact of the condition on work functioning and job satisfaction. Simple descriptive analysis and statistical techniques were used to interpret the data. RESULTS: One hundred and six participants participated (mean age: 37.49 ±â€…9.09). About 95% found it important to be able to work whilst receiving treatment and 82% of patients had reported at least a slight impact on their working ability due to their condition. Of the 31 patients for whom it was their first appointment, 77% said it would be useful to discuss the possible impacts their gynaecological condition could have on their work. About 66% (19/29) of the participants attending a follow-up appointment reported that their doctor had not discussed their work with them. CONCLUSIONS: The symptoms of gynaecological conditions can impact patients' ability to work. There is a lack of useful discussion from doctors about the perceived impact gynaecological conditions can have on a patient's ability to work, despite patients finding it important to be able to remain or return to work.


Assuntos
Ginecologia , Médicos , Adulto , Estudos Transversais , Humanos , Satisfação no Emprego , Pessoa de Meia-Idade , Inquéritos e Questionários
9.
J Anal Toxicol ; 45(8): 820-828, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34185831

RESUMO

Proving driving under the influence of cannabis (DUIC) is difficult. Establishing a biomarker of recent use to supplement behavioral observations may be a useful alternative strategy. We determined whether cannabinoid concentrations in blood, oral fluid (OF) or breath could identify use within the past 3 h-likely the period of the greatest impairment. In a randomized trial, 191 frequent (≥4/week) and occasional (<4/week) cannabis users smoked one cannabis (placebo [0.02%], or 5.9% or 13.4% Δ9-tetrahydrocannabinol [THC]) cigarette ad libitum. Blood, OF and breath samples were collected prior to and up to 6 h after smoking. Samples were analyzed for 10 cannabinoids in OF, 8 in blood and THC in breath. Frequent users had more residual THC in blood and were more likely to be categorized as 'recently used' prior to smoking; this did not occur in OF. Per se limits ranging from undetectable to 5 ng/mL THC in blood offered limited usefulness as biomarkers of recent use. Cannabinol (CBN, cutoff = 1 ng/mL) in blood offered 100% specificity but only 31.4% sensitivity, resulting in 100% positive predictive value (PPV) and 94.0% negative predictive value (NPV) at 4.3% prevalence; however, CBN may vary by cannabis chemovar. A 10 ng/mL THC cutoff in OF exhibited the overall highest performance to detect its use within 3 h (99.7% specificity, 82.4% sensitivity, 92.5% PPV and 99.2% NPV) but was still detectable in 23.2% of participants ∼4.4 h post-smoking, limiting specificity at later time points. OF THC may be a helpful indicator of recent cannabis intake, but this does not equate to impairment. Behavioral assessment of impairment is still required to determine DUIC. This study only involved cannabis inhalation, and additional research evaluating alternative routes of ingestion (i.e., oral) is needed.


Assuntos
Canabinoides , Cannabis , Fumar Maconha , Biomarcadores , Dronabinol , Humanos , Detecção do Abuso de Substâncias
10.
Eur J Nutr ; 60(8): 4439-4452, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34081167

RESUMO

PURPOSE: This study investigated metabolic benefits of protein hydrolysates from the macroalgae Palmaria palmata, previously shown to inhibit dipeptidylpeptidase-4 (DPP-4) activity in vitro. METHODS: Previously, Alcalase/Flavourzyme-produced P. palmata protein hydrolysate (PPPH) improved glycaemia and insulin production in streptozotocin-induced diabetic mice. Here the PPPH, was compared to alternative Alcalase, bromelain and Promod-derived hydrolysates and an unhydrolysed control. All PPPH's underwent simulated gastrointestinal digestion (SGID) to establish oral bioavailability. PPPH's and their SGID counterparts were tested in pancreatic, clonal BRIN-BD11 cells to assess their insulinotropic effect and associated intracellular mechanisms. PPPH actions on the incretin effect were assessed via measurement of DPP-4 activity, coupled with GLP-1 and GIP release from GLUTag and STC-1 cells, respectively. Acute in vivo effects of Alcalase/Flavourzyme PPPH administration on glucose tolerance and satiety were assessed in overnight-fasted mice. RESULTS: PPPH's (0.02-2.5 mg/ml) elicited varying insulinotropic effects (p < 0.05-0.001). SGID of the unhydrolysed protein control, bromelain and Promod PPPH's retained, or improved, bioactivity regarding insulin secretion, DPP-4 inhibition and GIP release. Insulinotropic effects were retained for all SGID-hydrolysates at higher PPPH concentrations. DPP-4 inhibitory effects were confirmed for all PPPH's and SGID counterparts (p < 0.05-0.001). PPPH's were shown to directly influence the incretin effect via upregulated GLP-1 and GIP (p < 0.01-0.001) secretion in vitro, largely retained after SGID. Alcalase/Flavourzyme PPPH produced the greatest elevation in cAMP (p < 0.001, 1.7-fold), which was fully retained post-SGID. This hydrolysate elicited elevations in intracellular calcium (p < 0.01) and membrane potential (p < 0.001). In acute in vivo settings, Alcalase/Flavourzyme PPPH improved glucose tolerance (p < 0.01-0.001) and satiety (p < 0.05-0.001). CONCLUSION: Bioavailable PPPH peptides may be useful for the management of T2DM and obesity.


Assuntos
Diabetes Mellitus Experimental , Peptídeo 1 Semelhante ao Glucagon , Animais , Glicemia , Polipeptídeo Inibidor Gástrico , Incretinas , Insulina/metabolismo , Camundongos , Hidrolisados de Proteína , Regulação para Cima
11.
J Dairy Sci ; 104(7): 8039-8049, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33934859

RESUMO

Greenhouse gas (GHG) emissions and nitrogen (N) efficiencies were modeled for 2 genetic groups (GG) of Holstein-Friesian cows across 3 contrasting feeding treatments (FT). The 2 GG were (1) high economic breeding index (EBI) animals representative of the top 5% of cows nationally (elite) and (2) EBI representative of the national average (NA). The FT represented (1) generous feeding of pasture, (2) a slight restriction in pasture allowance, and (3) a high-concentrate feeding system with adequate pasture allowance. Greenhouse gas and N balance models were parameterized using outputs generated from the Moorepark Dairy Systems model, a stochastic budgetary simulation model, having integrated biological data pertaining to the 6 scenarios (2 GG × 3 FT) obtained from a 4-yr experiment conducted between 2013 and 2016. On a per hectare basis, total system GHG emissions were similar for both elite and NA across the 3 FT. Per unit of product, however, the elite group had 10% and 11% lower GHG emissions per kilogram of fat- and protein-corrected milk and per kilogram of milk solids (MSO; fat + protein kg), respectively, compared with the NA across the 3 FT. The FT incorporating high concentrate supplementation had greater absolute GHG emissions per hectare as well as GHG per kilogram of fat- and protein-corrected milk and MSO. The elite group had a slightly superior N use efficiency (N output/N input) and lower N surplus (N input - N output) compared with the NA group. The high concentrate FT had an inferior N use efficiency and a higher N surplus. The results of the current study demonstrate that breeding for increased EBI will lead to a general improvement in GHG emissions per unit of product as well as improved N efficiency. The results also illustrate that reducing concentrate supplementation will reduce GHG emissions, GHG emissions intensity, while improving N efficiency in the context of pasture-based dairy production.


Assuntos
Indústria de Laticínios , Gases de Efeito Estufa , Ração Animal , Animais , Bovinos , Dieta , Feminino , Lactação , Leite , Nitrogênio , Estações do Ano
12.
Anim Microbiome ; 3(1): 7, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33500003

RESUMO

BACKGROUND: Aquaculture successfully meets global food demands for many fish species. However, aquaculture production of Atlantic cod (Gadus morhua) is just 2.5% of total market production. For cod farming to be a viable economic venture specific challenges on how to increase growth, health and farming productivity need to be addressed. Feed ingredients play a key role here. Macroalgae (seaweeds) have been suggested as a functional feed supplement with both health and economic benefits for terrestrial farmed animals and fish. The impact of such dietary supplements to cod gut integrity and microbiota, which contribute to overall fish robustness is unknown. The objective of this study was to supplement the diet of juvenile Atlantic cod with macroalgae and determine the impacts on fish condition and growth, gut morphology and hindgut microbiota composition (16S rRNA amplicon sequencing). Fish were fed one of three diets: control (no macroalgal inclusion), 10% inclusion of either egg wrack (Ascophyllum nodosum) or sea lettuce (Ulva rigida) macroalgae in a 12-week trial. RESULTS: The results demonstrated there was no significant difference in fish condition, gut morphology or hindgut microbiota between the U. rigida supplemented fish group and the control group at any time-point. This trend was not observed with the A. nodosum treatment. Fish within this group were further categorised as either 'Normal' or 'Lower Growth'. 'Lower Growth' individuals found the diet unpalatable resulting in reduced weight and condition factor combined with an altered gut morphology and microbiome relative to the other treatments. Excluding this group, our results show that the hindgut microbiota was largely driven by temporal pressures with the microbial communities becoming more similar over time irrespective of dietary treatment. The core microbiome at the final time-point consisted of the orders Vibrionales (Vibrio and Photobacterium), Bacteroidales (Bacteroidetes and Macellibacteroides) and Clostridiales (Lachnoclostridium). CONCLUSIONS: Our study indicates that U. rigida macroalgae can be supplemented at 10% inclusion levels in the diet of juvenile farmed Atlantic cod without any impact on fish condition or hindgut microbial community structure. We also conclude that 10% dietary inclusion of A. nodosum is not a suitable feed supplement in a farmed cod diet.

13.
Appl Radiat Isot ; 167: 109455, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33039762

RESUMO

The National Institute of Standards and Technology (NIST) performed new standardization measurements for 124I. As part of this work the absolute photon emission intensity for the main gamma-rays of 124I were determined using several high-purity germanium (HPGe) detectors. In addition, the half-life for 124I was also determined using an HPGe detector. Ionization chamber measurements were performed for additional sources, but it was not possible to obtain a precise half-life value.

14.
Ann Oncol ; 32(4): 522-532, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33359547

RESUMO

BACKGROUND: The incidence of esophageal adenocarcinoma (EAC) is rapidly rising and has a 5-year survival rate of <20%. Beyond TNM (tumor-node-metastasis) staging, no reliable risk stratification tools exist and no large-scale studies have profiled circulating tumor DNA (ctDNA) at relapse in EAC. Here we analyze the prognostic potential of ctDNA dynamics in EAC, taking into account clonal hematopoiesis with indeterminate potential (CHIP). PATIENTS AND METHODS: A total of 245 samples from 97 patients treated with neoadjuvant chemotherapy and surgery were identified from the prospective national UK Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS) consortium data set. A pan-cancer ctDNA panel comprising 77 genes was used. Plasma and peripheral blood cell samples were sequenced to a mean depth of 7082× (range 2196-28 524) and ctDNA results correlated with survival. RESULTS: Characteristics of the 97 patients identified were as follows: 83/97 (86%) male, median age 68 years (SD 9.5 years), 100% cT3/T4, 75% cN+. EAC-specific drivers had higher variant allele fractions than passenger mutations. Using stringent quality criteria 16/79 (20%) were ctDNA positive following resection; recurrence was observed in 12/16 (75%) of these. As much as 78/97 (80%) had CHIP analyses that enabled filtering for CHIP variants, which were found in 18/78 (23%) of cases. When CHIP was excluded, 10/63 (16%) patients were ctDNA positive and 9/10 of these (90%) recurred. With correction for CHIP, median cancer-specific survival for ctDNA-positive patients was 10.0 months versus 29.9 months for ctDNA-negative patients (hazard ratio 5.55, 95% confidence interval 2.42-12.71; P = 0.0003). Similar outcomes were observed for disease-free survival. CONCLUSIONS: We demonstrate in a large, national, prospectively collected data set that ctDNA in plasma following surgery for EAC is prognostic for relapse. Inclusion of peripheral blood cell samples can reduce or eliminate false positives from CHIP. In future, post-operative ctDNA could be used to risk stratify patients into high- and low-risk groups for intensification or de-escalation of adjuvant chemotherapy.


Assuntos
Adenocarcinoma , Neoplasias Esofágicas , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Idoso , Biomarcadores Tumorais , Neoplasias Esofágicas/genética , Humanos , Biópsia Líquida , Masculino , Recidiva Local de Neoplasia/genética , Estudos Prospectivos
15.
Appl Radiat Isot ; 163: 109216, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32561054

RESUMO

Re-entrant ionization chambers (ICs) are essential to radionuclide metrology and nuclear medicine for maintaining standards and measuring half-lives. The requirements of top-level metrology demand that systems must be precise and stable to 0.1 % over many years, and linear from 10-14 A to 10-8 A. Thus, laboratories depend on bespoke current measurement systems and often rely on sealed sources to generate reference currents. To maintain and improve present capabilities, metrologists need to overcome two looming challenges: ageing electronics and decreasing availability of sealed sources. Possible solutions using Ultrastable Low-Noise Current Amplifiers (ULCAs), resistive-feedback electrometers, and (quantum) single-electron pumps are reviewed. Broader discussions of IC design and methodology are discussed. ULCAs show promise and resistive-feedback systems which take advantage of standard resistor calibrations offer an alternative.

16.
Nat Commun ; 11(1): 1512, 2020 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-32251296

RESUMO

Studies of inflammatory bowel disease (IBD) have been inconclusive in relating microbiota with distribution of inflammation. We report microbiota, host transcriptomics, epigenomics and genetics from matched inflamed and non-inflamed colonic mucosa [50 Crohn's disease (CD); 80 ulcerative colitis (UC); 31 controls]. Changes in community-wide and within-patient microbiota are linked with inflammation, but we find no evidence for a distinct microbial diagnostic signature, probably due to heterogeneous host-microbe interactions, and show only marginal microbiota associations with habitual diet. Epithelial DNA methylation improves disease classification and is associated with both inflammation and microbiota composition. Microbiota sub-groups are driven by dominant Enterbacteriaceae and Bacteroides species, representative strains of which are pro-inflammatory in vitro, are also associated with immune-related epigenetic markers. In conclusion, inflamed and non-inflamed colonic segments in both CD and UC differ in microbiota composition and epigenetic profiles.


Assuntos
Colite Ulcerativa/imunologia , Doença de Crohn/imunologia , Epigênese Genética/imunologia , Microbioma Gastrointestinal/imunologia , Interações entre Hospedeiro e Microrganismos/imunologia , Adulto , Idoso , Bacteroides/genética , Bacteroides/imunologia , Bacteroides/isolamento & purificação , Biópsia , Células CACO-2 , Estudos de Casos e Controles , Estudos de Coortes , Colite Ulcerativa/genética , Colite Ulcerativa/microbiologia , Colite Ulcerativa/patologia , Colo/diagnóstico por imagem , Colo/imunologia , Colo/microbiologia , Colo/patologia , Colonoscopia , Doença de Crohn/genética , Doença de Crohn/microbiologia , Doença de Crohn/patologia , DNA Bacteriano/isolamento & purificação , Enterobacteriaceae/genética , Enterobacteriaceae/imunologia , Enterobacteriaceae/isolamento & purificação , Epigenômica , Feminino , Microbioma Gastrointestinal/genética , Interações entre Hospedeiro e Microrganismos/genética , Humanos , Mucosa Intestinal/diagnóstico por imagem , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Masculino , Pessoa de Meia-Idade , RNA Ribossômico 16S/genética , RNA-Seq , Adulto Jovem
18.
Br J Surg ; 107(8): 1042-1052, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31997313

RESUMO

BACKGROUND: Early cancer recurrence after oesophagectomy is a common problem, with an incidence of 20-30 per cent despite the widespread use of neoadjuvant treatment. Quantification of this risk is difficult and existing models perform poorly. This study aimed to develop a predictive model for early recurrence after surgery for oesophageal adenocarcinoma using a large multinational cohort and machine learning approaches. METHODS: Consecutive patients who underwent oesophagectomy for adenocarcinoma and had neoadjuvant treatment in one Dutch and six UK oesophagogastric units were analysed. Using clinical characteristics and postoperative histopathology, models were generated using elastic net regression (ELR) and the machine learning methods random forest (RF) and extreme gradient boosting (XGB). Finally, a combined (ensemble) model of these was generated. The relative importance of factors to outcome was calculated as a percentage contribution to the model. RESULTS: A total of 812 patients were included. The recurrence rate at less than 1 year was 29·1 per cent. All of the models demonstrated good discrimination. Internally validated areas under the receiver operating characteristic (ROC) curve (AUCs) were similar, with the ensemble model performing best (AUC 0·791 for ELR, 0·801 for RF, 0·804 for XGB, 0·805 for ensemble). Performance was similar when internal-external validation was used (validation across sites, AUC 0·804 for ensemble). In the final model, the most important variables were number of positive lymph nodes (25·7 per cent) and lymphovascular invasion (16·9 per cent). CONCLUSION: The model derived using machine learning approaches and an international data set provided excellent performance in quantifying the risk of early recurrence after surgery, and will be useful in prognostication for clinicians and patients.


ANTECEDENTES: la recidiva precoz del cáncer tras esofaguectomía es un problema frecuente con una incidencia del 20-30% a pesar del uso generalizado del tratamiento neoadyuvante. La cuantificación de este riesgo es difícil y los modelos actuales funcionan mal. Este estudio se propuso desarrollar un modelo predictivo para la recidiva precoz después de la cirugía para el adenocarcinoma de esófago utilizando una gran cohorte multinacional y enfoques con aprendizaje automático. MÉTODOS: Se analizaron pacientes consecutivos sometidos a esofaguectomía por adenocarcinoma y que recibieron tratamiento neoadyuvante en 6 unidades de cirugía esofagogástrica del Reino Unido y 1 de los Países Bajos. Con la utilización de características clínicas y la histopatología postoperatoria se generaron modelos mediante regresión de red elástica (elastic net regression, ELR) y métodos de aprendizaje automático Random Forest (RF) y XG boost (XGB). Finalmente, se generó un modelo combinado (Ensemble) de dichos métodos. La importancia relativa de los factores respecto al resultado se calculó como porcentaje de contribución al modelo. RESULTADOS: En total se incluyeron 812 pacientes. La tasa de recidiva a menos de 1 año fue del 29,1%. Todos los modelos demostraron una buena discriminación. Las áreas bajo la curva ROC (AUC) validadas internamente fueron similares, con el modelo Ensemble funcionando mejor (ELR = 0,791, RF = 0,801, XGB = 0,804, Ensemble = 0,805). El rendimiento fue similar cuando se utilizaba validación interna-externa (validación entre centros, Ensemble AUC = 0,804). En el modelo final, las variables más importantes fueron el número de ganglios linfáticos positivos (25,7%) y la invasión linfovascular (16,9%). CONCLUSIÓN: El modelo derivado con la utilización de aproximaciones con aprendizaje automático y un conjunto de datos internacional proporcionó un rendimiento excelente para cuantificar el riesgo de recidiva precoz tras la cirugía y será útil para clínicos y pacientes a la hora de establecer un pronóstico.


Assuntos
Adenocarcinoma/cirurgia , Regras de Decisão Clínica , Neoplasias Esofágicas/cirurgia , Esofagectomia , Aprendizado de Máquina , Recidiva Local de Neoplasia/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Medição de Risco
19.
Appl Radiat Isot ; 156: 108943, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31683089

RESUMO

The National Institute of Standards and Technology (NIST) measured the internal pair production branching ratio of 90Y using two sources and four high purity germanium (HPGe) detectors to detect the resulting annihilation radiation. The internal pair production branching ratio determined from these measurements, (32.0 ±â€¯1.5) × 10-6 (k = 1), agrees within 1 standard uncertainty with the recommended value of (32.6 ±â€¯0.7) × 10-6 (k = 1) from the DDEP database.

20.
J Dairy Sci ; 103(2): 1685-1700, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31837792

RESUMO

The objective of the current study was to examine phenotypic fertility performance and survival, and to gain insight into underlying factors that may contribute to greater fertility performance in 2 divergent genetic groups (GG) of Holstein-Friesian, selected using the Irish Economic Breeding Index (EBI). The GG were evaluated across 3 spring calving pasture-based feeding treatments (FT) over 4 yr. The 2 divergent GG were (1) high EBI; representative of the top 5% nationally (elite), and (2) EBI representative of the national average (NA). In each year, 90 elite and 45 NA cows were randomly allocated to 1 of 3 FT: control, lower grass allowance, and high concentrate. No interaction between GG and FT was observed for any of the measures of fertility investigated. The elite cows achieved significantly greater pregnancy rate to first service (+14.9 percentage points), and significantly greater pregnancy rates after 21, 42, and 84 d of breeding (+17.3, +15.2, and +9.6 percentage points, respectively) compared with NA. The number of services per cow was fewer for elite (1.57) compared with NA (1.80). The interval from mating start date to pregnancy was significantly shorter for elite cows compared with NA. The elite cows maintained greater mean body condition score than NA throughout the study (2.91 vs. 2.72), and had greater body condition score at calving, artificial insemination, and drying off compared with NA. The elite cows had greater mean circulating concentrations of insulin-like growth factor-1 compared with NA. No significant effect was observed of GG on commencement of luteal activity, or progesterone profile variables. Greater survival to the start of fifth lactation was observed for elite cows. The elite cows were 43% less likely to be culled than NA by the beginning of the fifth lactation. The results highlight the success of the Economic Breeding Index to deliver reproductive performance and longevity consistent with industry targets across a range of seasonal pasture-based FT. The results also clearly demonstrate the potential of appropriate genetic selection to reverse negative fertility trends incurred during previous decades of selection for milk production alone.


Assuntos
Bovinos/fisiologia , Indústria de Laticínios , Dieta/veterinária , Fertilidade , Animais , Cruzamento , Bovinos/genética , Bovinos/crescimento & desenvolvimento , Indústria de Laticínios/métodos , Feminino , Fertilidade/genética , Inseminação Artificial/veterinária , Lactação , Leite , Poaceae , Gravidez , Progesterona , Reprodução/genética , Estações do Ano
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