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AIM: To determine low-density lipoprotein cholesterol (LDL-C) screening frequency and levels, and factors associated with elevated LDL-C, in Australasian youth with type 1 diabetes (T1D). METHODS: Data were extracted from the Australasian Diabetes Data Network (ADDN), a prospective clinical quality registry, on all T1D healthcare visits attended by young people aged 16-25 years (with T1D duration of >1 year) between January 2011 and December 2020. The primary outcomes were elevated LDL-C > 2.6 mmol/L (100 mg/dL) and threshold for treatment: >3.4 mmol/L (130 mg/dL), according to consensus guidelines. Multivariable Generalised Estimated Equations (GEE) were used to examine factors associated with elevated LDL-C across all visits. RESULTS: A cohort of 6338 young people (52.6% men) were identified, of whom 1603 (25.3%) had ≥1 LDL-C measurement documented. At last measurement, mean age, age at T1D diagnosis and T1D duration were 18.3 ± 2.4, 8.8 ± 4.5 and 8.9 ± 4.8 years, respectively. LDL-C was elevated in 737 (46.0%) and at the treatment threshold in 250 (15.6%). In multivariable GEE elevated LDL-C continuously was associated with older age (OR = 0.07; 0.01-0.13, p = 0.02), female sex (OR = 0.31; 0.18-0.43; p < 0.001), higher HbA1c (OR = 0.04; 0.01-0.08; p = 0.01) and having an elevated BMI (OR = 0.17, 0.06-0.39, p < 0.001). CONCLUSIONS: LDL-C screening and levels are suboptimal in this cohort, increasing future cardiovascular complication risk. There is an urgent need to understand how healthcare services can support improved screening and management of dyslipidaemia in this population.
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Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 1 , Dislipidemias , Masculino , Humanos , Adolescente , Femenino , Adulto Joven , Diabetes Mellitus Tipo 1/tratamiento farmacológico , LDL-Colesterol , Estudios Prospectivos , Dislipidemias/epidemiología , Dislipidemias/tratamiento farmacológico , Enfermedades Cardiovasculares/epidemiologíaRESUMEN
BACKGROUND: Suboptimal or slow recruitment affects 30-50% of trials. Education and training of trial recruiters has been identified as one strategy for potentially boosting recruitment to randomised controlled trials (hereafter referred to as trials). The Training tRial recruiters, An educational INtervention (TRAIN) project was established to develop and assess the acceptability of an education and training intervention for recruiters to neonatal trials. In this paper, we report the development and acceptability of TRAIN. METHODS: TRAIN involved three sequential phases, with each phase contributing information to the subsequent phase(s). These phases were 1) evidence synthesis (systematic review of the effectiveness of training interventions and a content analysis of the format, content, and delivery of identified interventions), 2) intervention development using a Partnership (co-design/co-creation) approach, and 3) intervention acceptability assessments with recruiters to neonatal trials. RESULTS: TRAIN, accompanied by a comprehensive intervention manual, has been designed for online or in-person delivery. TRAIN can be offered to recruiters before trial recruitment begins or as refresher sessions during a trial. The intervention consists of five core learning outcomes which are addressed across three core training units. These units are the trial protocol (Unit 1, 50 min, trial-specific), understanding randomisation (Unit 2, 5 min, trial-generic) and approaching and engaging with parents (Unit 3, 70 min, trial-generic). Eleven recruiters to neonatal trials registered to attend the acceptability assessment training workshops, although only four took part. All four positively valued the training Units and resources for increasing recruiter preparedness, knowledge, and confidence. More flexibility in how the training is facilitated, however, was noted (e.g., training divided across two workshops of shorter duration). Units 2 and 3 were considered beneficial to incorporate into Good Clinical Practice Training or as part of induction training for new staff joining neonatal units. CONCLUSION: TRAIN offers a comprehensive co-produced training and education intervention for recruiters to neonatal trials. TRAIN was deemed acceptable, with minor modification, to neonatal trial recruiters. The small number of recruiters taking part in the acceptability assessment is a limitation. Scale-up of TRAIN with formal piloting and testing for effectiveness in a large cluster randomised trial is required.
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Selección de Paciente , Proyectos de Investigación , Humanos , Recién Nacido , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Autism spectrum disorder (ASD) is a behaviorally defined condition that manifests in infancy or early childhood as deficits in communication skills and social interactions. Often, restricted and repetitive behaviors (RRBs) accompany this disorder. ASD is polygenic and genetically complex, so we hypothesized that focusing analyses on intermediate core component phenotypes, such as RRBs, can reduce genetic heterogeneity and improve statistical power. Applying this approach, we mined Caucasian genome-wide association studies (GWAS) data from two of the largest ASD family cohorts, the Autism Genetics Resource Exchange and Autism Genome Project (AGP). Of the 12 RRBs measured by the Autism Diagnostic Interview-Revised, seven were found to be significantly familial and substantially variable, and hence, were tested for genome-wide association in 3104 ASD-affected children from 2045 families. Using a stringent significance threshold (P<7.1 × 10-9), GWAS in the AGP revealed an association between 'the degree of the repetitive use of objects or interest in parts of objects' and rs2898883 (P<6.8 × 10-9), which resides within the sixth intron of PHB. To identify the candidate target genes of the associated single-nucleotide polymorphisms at that locus, we applied chromosome conformation studies in developing human brains and implicated three additional genes: SLC35B1, CALCOCO2 and DLX3. Gene expression, brain imaging and fetal brain expression quantitative trait locus studies prioritize SLC35B1 and PHB. These analyses indicate that GWAS of single heritable features of genetically complex disorders followed by chromosome conformation studies in relevant tissues can be successful in revealing novel risk genes for single core features of ASD.
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Trastorno del Espectro Autista/genética , Cromosomas Humanos Par 17 , Conducta Compulsiva/genética , Adolescente , Adulto , Trastorno del Espectro Autista/metabolismo , Trastorno del Espectro Autista/psicología , Encéfalo/metabolismo , Niño , Preescolar , Femenino , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo/métodos , Edad Gestacional , Proteínas de Homeodominio/genética , Humanos , Masculino , Persona de Mediana Edad , Proteínas de Transporte de Monosacáridos/genética , Herencia Multifactorial , Proteínas Nucleares/genética , Polimorfismo de Nucleótido Simple , Prohibitinas , Sitios de Carácter Cuantitativo , Proteínas Represoras/genética , Factores de Transcripción/genética , TranscriptomaRESUMEN
Here, we investigate the feasibility and effectiveness of electrowetting in the motion control of droplets of different liquids, which are widely used as inks in direct writing (DW)-based three-dimensional (3D) printing processes for various applications. To control the movement of DW ink droplets on dielectric substrates, the electrodes were embedded in the substrate. It is demonstrated that droplets of pure liquid inks, aqueous polymer solution inks, and carbon fiber suspension inks can be moved on multi-angled surfaces. Also, experimental results reveal that droplets of a commercial hydrogel, agar-agar, alginate, xanthan gum, and gum arabic can be moved by electrowetting. Droplets of sizes 200 µm-3 mm were manipulated and moved by the electric field on different dielectric substrates accurately and repeatedly. Effective electrowetting-based control and movement of droplets were observed on horizontal, vertical, and even inverted substrates. These findings imply the feasibility and potential application of electrowetting as a flexible, rapid, and new method for ink droplet control in 3D printing processes.
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Although the cheetah is recognised as the fastest land animal, little is known about other aspects of its notable athleticism, particularly when hunting in the wild. Here we describe and use a new tracking collar of our own design, containing a combination of Global Positioning System (GPS) and inertial measurement units, to capture the locomotor dynamics and outcome of 367 predominantly hunting runs of five wild cheetahs in Botswana. A remarkable top speed of 25.9 m s(-1) (58 m.p.h. or 93 km h(-1)) was recorded, but most cheetah hunts involved only moderate speeds. We recorded some of the highest measured values for lateral and forward acceleration, deceleration and body-mass-specific power for any terrestrial mammal. To our knowledge, this is the first detailed locomotor information on the hunting dynamics of a large cursorial predator in its natural habitat.
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Aceleración , Acinonyx/fisiología , Locomoción/fisiología , Destreza Motora/fisiología , Conducta Predatoria/fisiología , Acelerometría/instrumentación , Animales , Animales Salvajes/fisiología , Botswana , Ecosistema , Sistemas de Información GeográficaRESUMEN
Several common alleles in the oxytocin receptor gene (OXTR) are associated with altered brain function in reward circuitry in neurotypical adults and may increase risk for autism spectrum disorders (ASD). Yet, it is currently unknown how variation in the OXTR relates to brain functioning in individuals with ASD, and, critically, whether neural endophenotypes vary as a function of aggregate genetic risk. Here, for we believe the first time, we use a multi-locus approach to examine how genetic variation across several OXTR single-nucleotide polymorphisms (SNPs) affect functional connectivity of the brain's reward network. Using data from 41 children with ASD and 41 neurotypical children, we examined functional connectivity of the nucleus accumbens (NAcc) - a hub of the reward network - focusing on how connectivity varies with OXTR risk-allele dosage. Youth with ASD showed reduced NAcc connectivity with other areas in the reward circuit as a function of increased OXTR risk-allele dosage, as well as a positive association between risk-allele dosage and symptom severity, whereas neurotypical youth showed increased NAcc connectivity with frontal brain regions involved in mentalizing. In addition, we found that increased NAcc-frontal cortex connectivity in typically developing youth was related to better scores on a standardized measure of social functioning. Our results indicate that cumulative genetic variation on the OXTR impacts reward system connectivity in both youth with ASD and neurotypical controls. By showing differential genetic effects on neuroendophenotypes, these pathways elucidate mechanisms of vulnerability versus resilience in carriers of disease-associated risk alleles.
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Trastorno del Espectro Autista/genética , Receptores de Oxitocina/genética , Adolescente , Alelos , Trastorno Autístico/genética , Encéfalo , Estudios de Casos y Controles , Niño , Femenino , Lóbulo Frontal , Dosificación de Gen/genética , Frecuencia de los Genes/genética , Variación Genética , Humanos , Masculino , Neuroimagen/métodos , Núcleo Accumbens/fisiopatología , Oxitocina/metabolismo , Polimorfismo de Nucleótido Simple/genética , Receptores de Oxitocina/metabolismo , Recompensa , Conducta SocialRESUMEN
Videolaryngoscopy (VL) may improve the success of orotracheal intubation compared with direct laryngoscopy (DL). We performed a systematic search of PubMed, Embase, and CENTRAL databases for studies comparing VL and DL for emergency orotracheal intubations outside the operating room. The primary outcome was rate of first-pass intubation, with subgroup analyses by location, device used, clinician experience, and clinical scenario. The secondary outcome was complication rates. Data are presented as [odds ratio (95% confidence intervals); P-values]. We identified 32 studies with 15 064 emergency intubations. There was no difference in first-pass intubation with VL compared with DL [OR=1.28, (0.99-1.65); P=0.06]. First-pass intubations were increased with VL compared with DL in the intensive care unit (ICU) [2.02 (1.43-2.85); P<0.001], and similar in the emergency department or pre-hospital setting. First-pass intubations were similar with GlideScope®, but improved with the CMAC® [1.32 (1.08-1.62); P=0.007] compared with DL. There was greater first-pass intubation with VL compared with DL amongst novice/trainee clinicians [OR=1.95 (1.45-2.64); P<0.001], but not amongst experienced clinicians or paramedics/nurses. There was no difference in first-pass intubation with VL compared with DL during cardiopulmonary resuscitation or trauma. VL compared with DL was associated with fewer oesophageal intubations [OR=0.32 (0.14-0.70); P=0.003], but more arterial hypotension [OR=1.49 (1.00-2.23); P=0.05]. In summary, VL compared with DL is associated with greater first-pass emergency intubation in the ICU and amongst less experienced clinicians, and reduces oesophageal intubations. However, VL is associated with greater incidence of arterial hypotension. Further trials investigating the utility of VL over DL in specific situations are required.
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Servicios Médicos de Urgencia/métodos , Servicio de Urgencia en Hospital , Intubación Intratraqueal/métodos , Laringoscopía/métodos , Grabación de Cinta de Video , Humanos , Intubación Intratraqueal/instrumentaciónRESUMEN
Recommendations for bovine mycoplasma culture CO2 concentrations are varied and were not empirically derived. The objective of this study was to determine whether the growth measures of bovine mycoplasma isolates differed when incubated in CO2 concentrations of 10 or 5% or in candle jars (2.7 ± 0.2% CO2). Growth of Mycoplasma bovis (n = 22), Mycoplasma californicum (n = 18), and other Mycoplasma spp. (n = 10) laboratory isolates was evaluated. Isolate suspensions were standardized to approximately 108 cfu/mL and serially diluted in pasteurized whole milk to achieve test suspensions of 102 and 106 cfu/mL. One hundred microliters of each test dilution was spread in duplicate onto the surface of a modified Hayflick's agar plate. Colony growth was enumerated on d 3, 5, and 7 of incubation. A mixed linear model included the fixed effects of CO2 treatment (2.7, 5, or 10%), species, day (3, 5, or 7), and their interactions, with total colony counts as the dependent variable. Carbon dioxide concentration did not significantly affect overall mycoplasma growth differences, but differences between species and day were present. Colony counts (log10 cfu/mL) of M. bovis were 2.6- and 1.6-fold greater than M. californicum and other Mycoplasma spp., respectively. Growth at 7 d of incubation was greater than d 3 and 5 for all species. These findings were confirmed using field isolates (n = 98) from a commercial veterinary diagnostic laboratory. Binary growth responses (yes/no) of the field isolates were not different between CO2 treatments but did differ between species and day of incubation. On average, 57% of all field isolates were detected by 3 d of incubation compared with 93% on d 7. These results suggest that the range of suitable CO2 culture conditions and incubation times for the common mastitis-causing Mycoplasma spp. may be broader than currently recommended.
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Dióxido de Carbono/metabolismo , Mastitis Bovina/microbiología , Infecciones por Mycoplasma/microbiología , Mycoplasma bovis/crecimiento & desarrollo , Animales , Dióxido de Carbono/análisis , Bovinos , Medios de Cultivo/análisis , Medios de Cultivo/metabolismo , Femenino , Infecciones por Mycoplasma/veterinaria , Mycoplasma bovis/metabolismoRESUMEN
Recent technological advances in the human food industry with respect to meat processing have decreased the availability of animal proteins to the pet food industry which typically formulates diets with an excess of animal protein. In the long term, this is not sustainable; thus, alternative protein sources need to be investigated. This study examined three canine diets, comparing a typical animal protein-based diet (control) with two experimental diets where the animal protein was substituted in part with vegetable protein (formulated based either on total protein or amino acid content) using a broiler model. Each diet was fed to six cages each containing two birds from day 15, 18 cages in total (36 birds). Excreta were collected from days 19 to 21. On day 23, birds were euthanized and weighed, and their ileal digesta were collected and pooled for each cage. In addition, one leg per cage was collected for evaluation of muscle mass. Results showed no significant difference in animal performance (feed intake or live weight gain) or muscle to leg proportion across the diets. Birds fed the control diet and the diet balanced for amino acid content exhibited the greatest coefficients of apparent metabolizability for nitrogen (p < .001). Birds fed the diets that contained partial replacement of animal with vegetable protein generally had greater ileal digestibility of amino acids compared to birds fed the control (animal protein) diet. Analysis of excreta showed no dietary difference in terms of dry matter content; however, birds fed the diet balanced for total protein and the diet balanced for amino acid content had significantly greater excreta nitrogen than the control (p = .038). Overall, the study suggests vegetable proteins when formulated based on amino acid content are a viable alternative to animal proteins in canine diets.
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Alimentación Animal/análisis , Pollos/fisiología , Dieta/veterinaria , Proteínas en la Dieta/análisis , Perros , Verduras/química , Aminoácidos/metabolismo , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Digestión/fisiología , Íleon/fisiologíaRESUMEN
Introduction BTH1677, a 1,3-1,6 beta-glucan immunomodulator, stimulates a coordinated anti-cancer immune response in combination with anti-tumor antibody therapies. This phase II study explored the efficacy, pharmacokinetics (PK), and safety of BTH1677 combined with cetuximab/carboplatin/paclitaxel in untreated stage IIIB/IV non-small cell lung cancer (NSCLC) patients. Methods Patients were randomized 2:1 to the BTH1677 arm (N=60; BTH1677, 4 mg/kg, weekly; cetuximab, initial dose 400 mg/m2 and subsequent doses 250 mg/m2, weekly; carboplatin, 6 mg/mL/min AUC (area-under-the-curve) by Calvert formula, once each 3-week cycle [Q3W]); and paclitaxel, 200 mg/m2, Q3W) or Control arm (N=30; cetuximab/carboplatin/paclitaxel as above). Carboplatin/paclitaxel was discontinued after 4-6 cycles; patients who responded or remained stable received maintenance therapy with BTH1677/cetuximab (BTH1677 arm) or cetuximab (Control arm). Investigator and blinded central radiology reviews were conducted. Efficacy assessments included objective response rate (ORR; primary endpoint), disease control rate, duration of objective response, time-to-progression and overall survival (OS); safety was assessed by adverse events (AEs). Potential biomarker analysis for BTH1677 response was also conducted. Results Compared to control treatment, the addition of BTH1677 numerically increased ORR by both investigator (47.8% vs 23.1%; p=0.0468) and central (36.6% vs 23.1%; p=0.2895) reviews. No other endpoints differed between arms. PK was consistent with previous studies. BTH1677 was well tolerated, with AEs expected of the backbone therapy predominating. Biomarker-positive patients displayed better ORR and OS than negative patients. Conclusions BTH1677 combined with cetuximab/carboplatin/paclitaxel was well tolerated and improved ORR as first-line treatment in patients with advanced NSCLC. Future patient selection by biomarker status may further improve efficacy ClinicalTrials.gov Identifier: NCT00874848.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carboplatino/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Cetuximab/uso terapéutico , Glucanos/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Paclitaxel/uso terapéutico , Adulto , Anciano , Antineoplásicos/efectos adversos , Antineoplásicos/sangre , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carboplatino/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Cetuximab/efectos adversos , Femenino , Glucanos/efectos adversos , Glucanos/sangre , Glucanos/farmacocinética , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/metabolismo , Masculino , Persona de Mediana Edad , Paclitaxel/efectos adversos , Resultado del TratamientoRESUMEN
Porcine oocytes and embryos contain substantial amounts of lipid, with little known regarding its metabolic role during development. This study investigated the role of lipid metabolism and the interaction between carbohydrate and lipid substrates in porcine embryos. Following in vitro fertilisation, presumptive zygotes were transferred to culture medium supplemented with L-carnitine, a co-factor required for the metabolism of fatty acids. In porcine zygote medium-3 (PZM-3), which contains pyruvate and lactate, 3mM L-carnitine was the only dose that improved cleavage rates compared with the control. In the absence of carbohydrates, all doses of L-carnitine from 1.5 to 12mM increased cleavage rates compared with the control. Culture in a PZM-3-based sequential media system (Days 0-3: pyruvate and lactate; Days 4-7: glucose) significantly increased blastocyst cell numbers compared with culture in standard PZM-3. Supplementing PZM-3 with 3mM L-carnitine produced blastocysts with cell numbers equivalent to those obtained in the sequential media system. After vitrification, the post-warming survival rates of blastocysts obtained in media supplemented with 3mM L-carnitine were significantly greater than those of blastocysts obtained in standard PZM-3. In conclusion, L-carnitine supplementation improved embryo development when the medium contained pyruvate and lactate or was lacking carbohydrates completely, indicating a role for fatty-acid metabolism when the embryo's requirements for carbohydrates are not adequately met.
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Carnitina/administración & dosificación , Medios de Cultivo , Técnicas de Cultivo de Embriones/veterinaria , Desarrollo Embrionario/efectos de los fármacos , Animales , Blastocisto/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Criopreservación , Técnicas de Cultivo de Embriones/métodos , Fertilización In Vitro , PorcinosRESUMEN
AIMS: To evaluate the relationship between gestational diabetes (GDM) and incidence of cancer in women within the first decade postpartum. METHODS: This population-based retrospective cohort study compared the risk of cancer in women with GDM with that of a matched control group comprising pregnant women without diabetes. We included women from Ontario, Canada aged 20-50 years with no history of cancer who had given birth between 1995 and 2008 (N = 149 049). Women with GDM (N = 49 684) were matched on age and year of giving birth, in a ratio of 1:2, to pregnant women without diabetes (N = 99 365). RESULTS: Over a median 8-year follow-up, there were a total of 2927 (1.5%) cancers. After adjustment for covariates, we found no significant difference in overall risk of cancer between women with GDM and matched control subjects; however, GDM was associated with a significantly greater risk of thyroid cancer (adjusted hazard ratio 1.24, 95% CI 1.05, 1.46) and a significantly lower risk of premenopausal breast cancer (hazard ratio 0.86, 95% CI 0.75, 0.98) compared with matched control subjects. CONCLUSIONS: This large population-based study did not find a greater risk of cancers among women with GDM during the first decade postpartum; however, GDM was associated with a higher risk of thyroid cancer and a lower risk of premenopausal breast cancer. Further studies are needed to confirm these findings.
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Diabetes Gestacional/fisiopatología , Periodo Posparto , Embarazo en Diabéticas/fisiopatología , Premenopausia , Neoplasias de la Tiroides/etiología , Adulto , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/etiología , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Estimación de Kaplan-Meier , Persona de Mediana Edad , Ontario/epidemiología , Embarazo , Sistema de Registros , Estudios Retrospectivos , Factores de Riesgo , Neoplasias de la Tiroides/epidemiología , Cobertura Universal del Seguro de Salud , Adulto JovenRESUMEN
AIM: To determine what proportion of women with gestational diabetes underestimate their diabetes risk and identify factors associated with low diabetes risk perception. METHODS: Participants included pregnant adult women with gestational diabetes between 2009 and 2012 across seven diabetes clinics in Ontario, Canada. Data were collected through chart review and a survey that included a diabetes risk perception question. RESULTS: Of the 614 of 902 women (68% response rate) with gestational diabetes, 89% correctly responded that gestational diabetes increases the risk for developing diabetes. However, 47.1% of women perceived themselves to be at low risk for developing diabetes within 10 years. On multivariable analysis, BMI < 25 kg/m(2) , absent previous gestational diabetes history, absent diabetes family history and absent insulin use were appropriately associated with low diabetes risk perception. However, compared with Caucasian ethnicity, high-risk ethnicity (Aboriginal, Latin American, West Indian, South Asian, Middle Eastern, Filipino, Black, Pacific Islander) [odds ratio (OR) 2.07; 95% CI 1.30-3.31] and East and South East Asian ethnicity (OR 2.01; 1.10-3.67) were associated with low diabetes risk perception. After further adjustment for immigration, only high-risk ethnicity remained a predictor of low diabetes risk perception (OR 1.86; 1.09-3.19), whereas East and South East Asian ethnicity did not (OR 1.67; 0.86-3.22). CONCLUSIONS: Although the majority of women recognized gestational diabetes as a risk factor for diabetes, almost half underestimated their personal high diabetes risk despite prenatal care. Furthermore, women from high-risk ethnic groups were more likely to underestimate their risk, even after adjusting for immigration. Interventions tailored to these groups are necessary to enhance perceived diabetes risk.
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Diabetes Mellitus Tipo 2/etiología , Diabetes Gestacional/etnología , Diabetes Gestacional/psicología , Etnicidad , Percepción , Adulto , Actitud Frente a la Salud , Estudios de Cohortes , Estudios Transversales , Diabetes Mellitus Tipo 2/etnología , Diabetes Mellitus Tipo 2/psicología , Etnicidad/psicología , Etnicidad/estadística & datos numéricos , Femenino , Humanos , Conocimiento , Ontario/epidemiología , Embarazo , Factores de Riesgo , Factores SocioeconómicosRESUMEN
Heifer rearing is one of the largest production expenses for dairy cattle operations, which is one reason milking operations outsource heifer rearing to custom developers. The cost of harvested feedstuffs is a major expense in heifer rearing. A possible way to lower feed costs is to graze dairy heifers, but little research exists on this topic in the mid-south United States. The objectives of this research were to determine the cost of feeding bred dairy heifers grazing native warm-season grasses (NWSG), with and without legumes, and compare the cost of grazing with the cost of rearing heifers using 3 traditional rations. The 3 rations were corn silage with soybean meal, corn silage with dry distillers grain, and a wet distillers grain-based ration. Bred Holstein heifers between 15- and 20-mo-old continuously grazed switchgrass (SG), SG with red clover (SG+RC), a big bluestem and Indiangrass mixture (BBIG), and BBIG with red clover (BBIG+RC) in Tennessee during the summer months. Total grazing days were calculated for each NWSG to determine the average cost/animal per grazing day. The average daily gain (ADG) was calculated for each NWSG to develop 3 harvested feed rations that would result in the same ADG over the same number of grazing day as each NWSG treatment. The average cost/animal per grazing day was lowest for SG ($0.48/animal/grazing d) and highest for BBIG+RC ($1.10/animal/grazing d). For both BBIG and SG, legumes increased the average cost/animal per grazing day because grazing days did not increase enough to account for the additional cost of the legumes. No difference was observed in ADG for heifers grazing BBIG (0.85 kg/d) and BBIG+RC (0.94 kg/d), and no difference was observed in ADG for heifers grazing SG (0.71 kg/d) and SG+RC (0.70 kg/d). However, the ADG for heifers grazing SG and SG+RC was lower than the ADG for heifers grazing either BBIG or BBIG+RC. The average cost/animal per grazing day was lower for all NWSG treatments than the average cost/animal per day for all comparable feed rations at a low, average, and high yardage fee. Results of this study suggest that SG was the most cost-effective NWSG alternative to harvested feeds for bred dairy heifer rearing.
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Bovinos/fisiología , Industria Lechera/economía , Ensilaje/economía , Animales , Cruzamiento , Costos y Análisis de Costo , Fabaceae , Femenino , Panicum , Tennessee , Trifolium , Zea maysRESUMEN
AIM: To develop and validate a simple, reproducible method to assess dural sac size using standard imaging technology. MATERIALS AND METHODS: This study was institutional review board-approved. Two readers, blinded to the diagnoses, measured anterior-posterior (AP) and transverse (TR) dural sac diameter (DSD), and AP vertebral body diameter (VBD) of the lumbar vertebrae using MRI images from 53 control patients with pre-existing MRI examinations, 19 prospectively MRI-imaged healthy controls, and 24 patients with Marfan syndrome with prior MRI or CT lumbar spine imaging. Statistical analysis utilized linear and logistic regression, Pearson correlation, and receiver operating characteristic (ROC) curves. RESULTS: AP-DSD and TR-DSD measurements were reproducible between two readers (r = 0.91 and 0.87, respectively). DSD (L1-L5) was not different between male and female controls in the AP or TR plane (p = 0.43; p = 0.40, respectively), and did not vary by age (p = 0.62; p = 0.25) or height (p = 0.64; p = 0.32). AP-VBD was greater in males versus females (p = 1.5 × 10(-8)), resulting in a smaller dural sac ratio (DSR) (DSD/VBD) in males (p = 5.8 × 10(-6)). Marfan patients had larger AP-DSDs and TR-DSDs than controls (p = 5.9 × 10(-9); p = 6.5 × 10(-9), respectively). Compared to DSR, AP-DSD and TR-DSD better discriminate Marfan from control subjects based on area under the curve (AUC) values from unadjusted ROCs (AP-DSD p < 0.01; TR-DSD p = 0.04). CONCLUSION: Individual vertebrae and L1-L5 (average) AP-DSD and TR-DSD measurements are simple, reliable, and reproducible for quantitating dural sac size without needing to control for gender, age, or height.
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Pesos y Medidas Corporales/métodos , Duramadre/anatomía & histología , Duramadre/patología , Vértebras Lumbares/anatomía & histología , Vértebras Lumbares/patología , Imagen por Resonancia Magnética/métodos , Síndrome de Marfan/patología , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Estatura , Peso Corporal , Femenino , Humanos , Región Lumbosacra/anatomía & histología , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Estándares de Referencia , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
We characterize the development of intrinsic connectivity networks (ICNs) from 4 to 9months of age with resting state magnetic resonance imaging performed on sleeping infants without sedative medication. Data is analyzed with independent component analysis (ICA). Using both low (30 components) and high (100 components) ICA model order decompositions, we find that the functional network connectivity (FNC) map is largely similar at both 4 and 9months. However at 9months the connectivity strength decreases within local networks and increases between more distant networks. The connectivity within the default-mode network, which contains both local and more distant nodes, also increases in strength with age. The low frequency power spectrum increases with age only in the posterior cingulate cortex and posterior default mode network. These findings are consistent with a general developmental pattern of increasing longer distance functional connectivity over the first year of life and raise questions regarding the developmental importance of the posterior cingulate at this age.
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Envejecimiento/fisiología , Encéfalo/fisiología , Conectoma/métodos , Interpretación de Imagen Asistida por Computador/métodos , Red Nerviosa/fisiología , Plasticidad Neuronal/fisiología , Sueño/fisiología , Niño , Preescolar , Femenino , Humanos , Estudios Longitudinales , Masculino , Vías Nerviosas/fisiología , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
AIMS: Since the first description of the classical presentation of progressive supranuclear palsy (PSP) in 1963, now known as Richardson's syndrome (PSP-RS), several distinct clinical syndromes have been associated with PSP-tau pathology. Like other neurodegenerative disorders, the severity and distribution of phosphorylated tau pathology are closely associated with the clinical heterogeneity of PSP variants. PSP with corticobasal syndrome presentation (PSP-CBS) was reported to have more tau load in the mid-frontal and inferior-parietal cortices than in PSP-RS. However, it is uncertain if differences exist in the distribution of tau pathology in other brain regions or if the overall tau load is increased in the brains of PSP-CBS. METHODS: We sought to compare the clinical and pathological features of PSP-CBS and PSP-RS including quantitative assessment of tau load in 15 cortical, basal ganglia and cerebellar regions. RESULTS: In addition to the similar age of onset and disease duration, we demonstrated that the overall severity of tau pathology was the same between PSP-CBS and PSP-RS. We identified that there was a shift of tau burden towards the cortical regions away from the basal ganglia; supporting the notion that PSP-CBS is a 'cortical' PSP variant. PSP-CBS also had less severe neuronal loss in the dorsolateral and ventrolateral subregions of the substantia nigra and more severe microglial response in the corticospinal tract than in PSP-RS; however, neuronal loss in subthalamic nucleus was equally severe in both groups. CONCLUSIONS: A better understanding of the factors that influence the selective pathological vulnerability in different PSP variants will provide further insights into the neurodegenerative process underlying tauopathies.
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Ganglios Basales/patología , Corteza Cerebral/patología , Parálisis Supranuclear Progresiva/patología , Proteínas tau/metabolismo , Edad de Inicio , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Parálisis Supranuclear Progresiva/diagnóstico , SíndromeRESUMEN
Copy number variants (CNVs) have a major role in the etiology of autism spectrum disorders (ASD), and several of these have reached statistical significance in case-control analyses. Nevertheless, current ASD cohorts are not large enough to detect very rare CNVs that may be causative or contributory (that is, risk alleles). Here, we use a tiered approach, in which clinically significant CNVs are first identified in large clinical cohorts of neurodevelopmental disorders (including but not specific to ASD), after which these CNVs are then systematically identified within well-characterized ASD cohorts. We focused our initial analysis on 48 recurrent CNVs (segmental duplication-mediated 'hotspots') from 24 loci in 31 516 published clinical cases with neurodevelopmental disorders and 13 696 published controls, which yielded a total of 19 deletion CNVs and 11 duplication CNVs that reached statistical significance. We then investigated the overlap of these 30 CNVs in a combined sample of 3955 well-characterized ASD cases from three published studies. We identified 73 deleterious recurrent CNVs, including 36 deletions from 11 loci and 37 duplications from seven loci, for a frequency of 1 in 54; had we considered the ASD cohorts alone, only 58 CNVs from eight loci (24 deletions from three loci and 34 duplications from five loci) would have reached statistical significance. In conclusion, until there are sufficiently large ASD research cohorts with enough power to detect very rare causative or contributory CNVs, data from larger clinical cohorts can be used to infer the likely clinical significance of CNVs in ASD.
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Trastornos Generalizados del Desarrollo Infantil/genética , Dosificación de Gen , Trastorno Autístico/epidemiología , Trastorno Autístico/genética , Causalidad , Trastornos Generalizados del Desarrollo Infantil/epidemiología , Anomalías Congénitas/epidemiología , Anomalías Congénitas/genética , Minería de Datos , Discapacidades del Desarrollo/epidemiología , Discapacidades del Desarrollo/genética , Eliminación de Gen , Duplicación de Gen , Estudios de Asociación Genética , Heterogeneidad Genética , Predisposición Genética a la Enfermedad , Recombinación Homóloga , Humanos , Prevalencia , Tamaño de la MuestraRESUMEN
BACKGROUND: Central nervous system primitive neuroectodermal tumours (CNS PNETs) are embryonal tumours occurring predominantly in children. Current lack of knowledge regarding their underlying biology hinders development of more effective treatments. We previously identified WNT/ß-catenin pathway activation in one-third of CNS PNETs, which was potentially linked to a better prognosis. In this study, we have extended our cohort, achieving a statistically significant correlation with prognosis. We additionally investigated the biological effects of WNT/ß-catenin pathway activation in tumour pathogenesis. METHODS: A total of 42 primary and 8 recurrent CNS PNETs were analysed for WNT/ß-catenin pathway status using ß-catenin immunohistochemistry. Genomic copy number and mRNA expression data were analysed to identify a molecular profile linked to WNT/ß-catenin pathway activation. RESULTS: Pathway activation was seen in 26% of CNS PNETs and was significantly associated with longer overall survival. Genes displaying a significant difference in expression levels, between tumours with and without WNT/ß-catenin pathway activation, included several involved in normal CNS development suggesting aberrant pathway activation may be disrupting this process. CONCLUSION: We have identified WNT/ß-catenin pathway status as a marker, which could potentially be used to stratify disease risk for patients with CNS PNET. Gene expression data suggest pathway activation is disrupting normal differentiation in the CNS.
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Neoplasias del Sistema Nervioso Central/genética , Tumores Neuroectodérmicos Primitivos/genética , Vía de Señalización Wnt/fisiología , beta Catenina/fisiología , Neoplasias del Sistema Nervioso Central/diagnóstico , Neoplasias del Sistema Nervioso Central/metabolismo , Neoplasias del Sistema Nervioso Central/mortalidad , Niño , Dosificación de Gen , Regulación Neoplásica de la Expresión Génica , Humanos , Análisis por Micromatrices , Tumores Neuroectodérmicos Primitivos/diagnóstico , Tumores Neuroectodérmicos Primitivos/metabolismo , Tumores Neuroectodérmicos Primitivos/mortalidad , Estudios Retrospectivos , Análisis de Supervivencia , Transcriptoma , Células Tumorales Cultivadas , Vía de Señalización Wnt/genética , beta Catenina/genética , beta Catenina/metabolismoRESUMEN
Human neural progenitors from a variety of sources present new opportunities to model aspects of human neuropsychiatric disease in vitro. Such in vitro models provide the advantages of a human genetic background combined with rapid and easy manipulation, making them highly useful adjuncts to animal models. Here, we examined whether a human neuronal culture system could be utilized to assess the transcriptional program involved in human neural differentiation and to model some of the molecular features of a neurodevelopmental disorder, such as autism. Primary normal human neuronal progenitors (NHNPs) were differentiated into a post-mitotic neuronal state through addition of specific growth factors and whole-genome gene expression was examined throughout a time course of neuronal differentiation. After 4 weeks of differentiation, a significant number of genes associated with autism spectrum disorders (ASDs) are either induced or repressed. This includes the ASD susceptibility gene neurexin 1, which showed a distinct pattern from neurexin 3 in vitro, and which we validated in vivo in fetal human brain. Using weighted gene co-expression network analysis, we visualized the network structure of transcriptional regulation, demonstrating via this unbiased analysis that a significant number of ASD candidate genes are coordinately regulated during the differentiation process. As NHNPs are genetically tractable and manipulable, they can be used to study both the effects of mutations in multiple ASD candidate genes on neuronal differentiation and gene expression in combination with the effects of potential therapeutic molecules. These data also provide a step towards better understanding of the signaling pathways disrupted in ASD.