Emergency Heart failure Mortality Risk Grade may help to reduce heart failure admissions.

INTRODUCTION: Hospital admissions for heart failure (HF) are frequent and pose a heavy burden on health care resources. Currently, the decision to hospitalise is based on clinical judgement rather than on prognostic risk stratification. The Emergency Heart failure Mortality Risk Grade (EHMRG) was recently developed to identify high-risk HF patients in the emergency department (ED). OBJECTIVE: To assess the ability of the EHMRG to predict 30-day mortality in Dutch HF patients visiting the ED and to evaluate whether the EHMRG could help to reduce the number of hospital admissions for decompensated HF. METHODS: Patients visiting the ED for decompensated HF were included. The decision to hospitalise or discharge was based on clinical judgement. The EHMRG was calculated retrospectively. Based on their EHMRG, patients were stratified as very low risk, low risk, intermediate risk, high risk and very high risk. RESULTS: In 227 patients (age 73 ± 12 years, 69% male) 30-day mortality was 11%. Mortality differed significantly among the EHMRG risk groups at 7­day (p = 0.012) and 30-day follow-up (p < 0.01). Based on clinical judgement, 76% of patients were hospitalised. If decision-making had been based on EHMRG, the hospitalisation rate could have been reduced to 66% (p < 0.01), particularly by reducing hospitalisations in patients at low risk of death. Mortality in discharged patients, whether the decision was based on EHMRG or clinical judgement, was 0%. CONCLUSION: The EHMRG accurately differentiates between high- and low-risk decompensated HF patients visiting the ED, making it a promising tool to safely reduce the number of HF admissions.

Determination of relationships between rumination and milk fat concentration and fatty acid profile using data from commercial rumination sensing systems.

Milk fat production is highly influenced by nutrition and rumen fermentation. Rumination is an essential part of the ruminant digestive process and can serve as an indicator of rumen fermentation. The objective of this research was to quantify variation in rumination time between and within dairy herds and test for relationships between rumination time and milk fat production and fatty acid (FA) profile as a proxy of rumen fermentation. Our hypothesis was that rumination may indicate disruptions to rumen fermentation and that cows that spent less time ruminating would have lower milk fat due to these rumen disruptions. Data were collected from 1,733 Holstein cows on 5 commercial dairy farms (4 in Pennsylvania and 1 in New York) of 200 to 700 head using 1 of 2 commercially-available rumination sensing systems, CowManager SensOor ear tags (Agis Automatisering BV) or SCR model HR-LDn neck collars (SCR Engineers). Rumination data were collected for 7 consecutive days leading up to a DHIA test, summed within day, then averaged to obtain mean daily minutes of rumination time. Milk samples from the DHIA test were analyzed for fat content by mid-infrared spectroscopy and for milk FA profile by gas chromatography. Rumination data were analyzed using multiple linear regression models. Rumination time was related to concentration of specific odd- and branched-chain and trans FA in milk but was not directly related to milk fat concentration. Rumination time also did not contribute to models predicting milk fat concentration after accounting for other cow-level variables. There was a linear relationship between trans-10 C18:1 and rumination time that was positive after accounting for the effect of farm (partial R2 of 2.97% across all data, 4.24% in SCR data, and 2.22% in CowManager data). Although rumination time was not related directly to milk fat, it was associated with differences in trans and odd- and branched-chain FA that have been demonstrated to change during subacute ruminal acidosis or biohydrogenation-induced milk fat depression, which may affect milk fat and other production variables. These associations suggest that further investigation into using rumination data from commercial systems to predict or identify the presence of these conditions is warranted.

Twelve years of circulatory extracorporeal life support at the University Medical Centre Utrecht.

INTRODUCTION: Circulatory extracorporeal life support (ECLS) has been performed at the University Medical Centre Utrecht for 12 years. During this time, case mix, indications, ECLS set-ups and outcomes seem to have substantially changed. We set out to describe these characteristics and their evolution over time. METHODS: All patients receiving circulatory ECLS between 2007 and 2018 were retrospectively identified and divided into six groups according to a 2-year period of time corresponding to the date of ECLS initiation. General characteristics plus data pertaining to comorbidities, indications and technical details of ECLS commencement as well as in-hospital, 30-day, 1­year and overall mortality were collected. Temporal trends in these characteristics were examined. RESULTS: A total of 347 circulatory ECLS runs were performed in 289 patients. The number of patients and ECLS runs increased from 8 till a maximum of 40 runs a year. The distribution of circulatory ECLS indications shifted from predominantly postcardiotomy to a wider set of indications. The proportion of peripheral insertions with or without application of left ventricular unloading techniques substantially increased, while in-hospital, 30-day, 1­year and overall mortality decreased over time. CONCLUSION: Circulatory ECLS was increasingly applied at the University Medical Centre Utrecht. Over time, indications as well as treatment goals broadened, and cannulation techniques shifted from central to mainly peripheral approaches. Meanwhile, weaning success increased and mortality rates diminished.

Relationships between milk fat and rumination time recorded by commercial rumination sensing systems.

Low rumination in the dairy cow is often assumed to result in reduction of saliva flow, rumen buffering, and milk fat, which is a major contributor to milk value in many pricing systems. Rumination time (RT) of individual cows can be measured with commercial rumination sensing systems, but our understanding of how daily RT (minutes per day) is related to milk fat production is limited. Our hypothesis was that between cows within a herd, greater RT would be associated with lower milk fat concentration. Data from 1,823 cows on 2 commercial dairy farms in Pennsylvania over 8 DHIA tests were analyzed for a total of 8,587 cow test-days. Rumination was measured on farm A with CowManager SensoOr ear tags (Agis Automatisering BV, Harmelen, the Netherlands) and on farm B with SCR Hi-Tag neck collars (SCR Engineers, Netanya, Israel). Rumination data were collected for 7 consecutive days leading up to each DHIA test, summed within day, and averaged across days. Data were analyzed using linear mixed models with a repeated effect of test day. Daily RT reported by commercial rumination systems varied across and within cows and was strongly influenced by a cow effect. Greater RT tended to be associated with a small decrease in milk fat concentration in farm A, but was not related to milk fat in farm B. The reason for this difference is unclear, but may be related to a potentially greater prevalence of biohydrogenation-induced milk fat depression on farm A. The significant, but small, model coefficients for milk fat and RT indicate that the relationship between these variables may not be strong enough to permit identification of cows with biohydrogenation-induced milk fat depression based on RT from commercial systems alone. Research assessing changes in rumination before, during, and after onset of altered rumen fermentation is necessary to determine whether RT could be used to identify cows with altered rumen fermentation.

The selective 5-HT6 receptor antagonist SLV has putative cognitive- and social interaction enhancing properties in rodent models of cognitive impairment.

In the present study, our aim was to investigate whether the novel highly selective 5-hydroxytryptamine6 (5-HT6) receptor antagonist SLV can ameliorate impairments in cognition and social interaction with potential relevance for both schizophrenia and Alzheimer's disease (AD). SLV sub-chronically - treated Wistar rats reared in isolation showed significantly enhanced prepulse inhibition (PPI) and object recognition performance when compared to vehicle - treated rats. In the isolated rats, also a significant reduction in expression of hippocampal neural cell adhesion molecule polysialylation (NCAM-PSA) was found which was ameliorated following treatment with SLV (30mg/kg). The social engagement deficit in rats exposed in utero (on gestational day 12.5) to valproic acid (VPA) was reversed by treatment with SLV (30mg/kg). SLV (20 and 30mg/kg, p.o.) fully reversed MK-801 - induced deficits in the ORT and also scopolamine - induced deficits in both the Object Recognition Task (ORT) and Object Location Task (OLT) in Wistar rats. In addition, a combination of sub-optimal doses of SLV and donepezil attenuated scopolamine-induced ORT deficits. Furthermore, SLV (10mg/kg, p.o.) reversed spontaneous alternation deficits in the T-maze induced by MK-801 administration in Swiss mice and in aged C57Bl/6J mice. SLV additionally improved T-Maze spatial learning and passive avoidance learning in Sprague-Dawley rats with amyoid-beta (Aß) injections into the hippocampus. In contrast, no benefits were found with SLV or the tested reference compounds (donepezil and RVT-101) on cognitive performance of 12months old Tg2576 mice. Also, in the social recognition task, an absence of cognitive enhancing properties was observed with SLV on "normal forgetting" in Wistar rats. Finally, analysis of spontaneous inhibitory postsynaptic currents (sIPSCs) frequency recorded from pyramidal cells revealed a reduction in the presence of 1µM of SLV. In conclusion, SLV was investigated in several rodent animal models and found to be effective at a least effective dose (LED) of 20mg/kg and 10mg/kg (p.o.) in the rat and the mouse, respectively.

The total cost of rearing a heifer on Dutch dairy farms: calculated versus perceived cost.

BACKGROUND: As farmers do not often keep a record of the expenditures for rearing, an economic tool that provides insight into the cost of rearing is useful. In the Netherlands, an economic tool (Jonkos) has been developed that can be used by farmers to obtain insight into the cost of rearing on their farm. The first objective of this study is to calculate the total cost of rearing young stock in Dutch dairy herds using Jonkos. The second objective is to compare the calculated total cost of rearing with the farmers' own estimation of the cost of rearing (the perceived cost). FINDINGS: Information was available for 75 herds that reared their own young stock and who had used the Jonkos tool. The perceived cost of rearing young stock was only available for 36 herds. In the 75 herds, the average herd size was 100 dairy cows. The average calculated total cost of rearing a heifer was €1,790. The average perceived total cost of rearing a heifer (including labour and housing costs) was €1,030. CONCLUSION: Most Dutch farmers in the study underestimated the total cost of rearing. The Jonkos economic tool has the advantage that herd-specific information can be entered as input values. The output of the tool can improve the awareness of farmers about the total costs of rearing. This awareness can lead to a higher priority of young stock rearing and consequently to an improved quality of young stock rearing.

CTA with fluoroscopy image fusion guidance in endovascular complex aortic aneurysm repair.

OBJECTIVES: To evaluate the effect of intraoperative guidance by means of live fluoroscopy image fusion with computed tomography angiography (CTA) on iodinated contrast material volume, procedure time, and fluoroscopy time in endovascular thoraco-abdominal aortic repair. METHODS: CTA with fluoroscopy image fusion road-mapping was prospectively evaluated in patients with complex aortic aneurysms who underwent fenestrated and/or branched endovascular repair (FEVAR/BEVAR). Total iodinated contrast material volume, overall procedure time, and fluoroscopy time were compared between the fusion group (n = 31) and case controls (n = 31). Reasons for potential fusion image inaccuracy were analyzed. RESULTS: Fusion imaging was feasible in all patients. Fusion image road-mapping was used for navigation and positioning of the devices and catheter guidance during access to target vessels. Iodinated contrast material volume and procedure time were significantly lower in the fusion group than in case controls (159 mL [95% CI 132-186 mL] vs. 199 mL [95% CI 170-229 mL], p = .037 and 5.2 hours [95% CI 4.5-5.9 hours] vs. 6.3 hours (95% CI 5.4-7.2 hours), p = .022). No significant differences in fluoroscopy time were observed (p = .38). Respiration-related vessel displacement, vessel elongation, and displacement by stiff devices as well as patient movement were identified as reasons for fusion image inaccuracy. CONCLUSION: Image fusion guidance provides added value in complex endovascular interventions. The technology significantly reduces iodinated contrast material dose and procedure time.

Coronary artery-bronchial artery fistulas: report of two Dutch cases with a review of the literature.

BACKGROUND: Coronary bronchial artery fistulas (CBFs) are rare anomalies, which may be isolated or associated with other disorders. MATERIALS AND METHODS: Two adult patients with CBFs are described and a PubMed search was performed using the keywords "coronary bronchial artery fistulas" in the period from 2008 to 2013. RESULTS: Twenty-seven reviewed subjects resulting in a total of 31 fistulas were collected. Asymptomatic presentation was reported in 5 subjects (19 %), chest pain (n = 17) was frequently present followed by haemoptysis (n = 7) and dyspnoea (n = 5). Concomitant disorders were bronchiectasis (44 %), diabetes (33 %) and hypertension (28 %). Multimodality and single-modality diagnostic strategies were applied in 56 % and 44 %, respectively. The origin of the CBFs was the left circumflex artery in 61 %, the right coronary artery in 36 % and the left anterior descending artery in 3 %. Management was conservative (22 %), surgical ligation (11 %), percutaneous transcatheter embolisation (30 %), awaiting lung transplantation (7 %) or not reported (30 %). CONCLUSIONS: CBFs may remain clinically silent, or present with chest pain or haemoptysis. CBFs are commonly associated with bronchiectasis and usually require a multimodality approach to be diagnosed. Several treatment strategies are available. This report presents two adult cases with CBFs and a review of the literature.

Time requirements and health effects of participation in colorectal cancer screening with colonoscopy or computed tomography colonography in a randomized controlled trial.

BACKGROUND AND STUDY AIMS: Time limitations and unwanted health effects may act as barriers to participation in colorectal cancer (CRC) screening. The aim of the study was to measure the time requirements and health effects of colonoscopy and computed tomography colonography (CTC) screening. PATIENTS AND METHODS: This was a prospective diary study in a consecutive sample within a randomized controlled CRC screening trial, comparing primary colonoscopy and CTC screening for average-risk individuals aged 50 - 74 years. The diary ended when all screening-related complaints had passed. RESULTS: The diary was returned by 75 % (241/322) of colonoscopy and 75 % (127/170) of CTC screenees. The median interval between leaving home and returning from the examination was longer for colonoscopy (4 hours and 18 minutes [4:18], interquartile range [IQR] 3:30 - 5:00) than for CTC (2:30 hours, IQR 2:06 - 3:00; P < 0.001). Similarly, the time to return to routine activities was longer after colonoscopy (3:54 hours, IQR 1:48 - 15:00) than after CTC (1:36 hours, IQR 0:54 - 4:42). The duration of screening-related symptoms after the examination was shorter for colonoscopy (11:00 hours, IQR 2:54 - 20:00) than for CTC (22:00 hours; IQR 5:30 - 47:00; P < 0.001). Abdominal complaints were reported more frequently after CTC. Anxiety, pain, and quality of life worsened during the screening process, with no differences between the two examinations. CONCLUSIONS: Compared with colonoscopy, CTC screening required less time and allowed screenees to return to their daily activities more quickly. In contrast, CTC was associated with a twofold longer duration of screening-related symptoms. Feelings of anxiety, pain, and quality of life scores were similar during colonoscopy and CTC screening. These results should be incorporated into cost-effectiveness analyses of CRC screening techniques.

Unit costs in population-based colorectal cancer screening using CT colonography performed in university hospitals in The Netherlands.

OBJECTIVES: Computed tomography (CT) colonography cost assumptions so far ranged from 346 to 594 per procedure, based on clinical CT reimbursement rates. The aim of our study was to estimate the costs in a screening situation. METHODS: Data were collected within an invitational population-based CRC screening trial (n = 2,920, age 50-75 years) with a dedicated CT-screening setting. Unit costs were calculated per action, per invitee and per participant (depending on adherence) and per individual with detected advanced neoplasia. Sensitivity analyses were performed, and alternative scenarios were considered. RESULTS: Of the invitees, 47.2 % were reminded, 38.8 % scheduled for an intake, 37.2 % scheduled for CT colonography, 33.6 % underwent CT colonography and 1.1 % needed a re-examination. Lesions ≥ 10 mm were detected in 2.9 % of the invitees. Invitation costs were Euro 5.57. Costs per CT colonography (intake to results) were Euro 144.00. Extra costs of communication of positive results were Euro 9.00. Average costs of invitational-based CT colonography screening were Euro 56.97 per invitee, Euro 169.40 per participant and Euro 2,772.51 per individual with detected advanced neoplasia. CONCLUSIONS: Dutch costs of CT-screening were substantially lower than the cost assumptions that were used in published cost-effectiveness analyses on CT colonography screening. This finding indicates that previous cost-effectiveness analyses should be updated, at least for the Dutch situation.

Plasma levels of matrix metalloproteinase-9: a possible diagnostic marker of successful endovascular aneurysm repair.

OBJECTIVE: The aim of the study was evaluating the diagnostic value of plasma matrix metalloproteinase- (MMP)-2 and -9 and tissue inhibitor of MMP-1 (TIMP-1) for endoleak detection after endovascular aneurysm repair (EVAR). REPORT: Consecutive EVAR patients (n = 17) with endoleak and matched controls without endoleak (n = 20) were prospectively enrolled. Increased levels of MMP-9 were observed in patients with endoleak (P < 0.001). Regression analysis showed no significant influence of age, sex or abdominal aortic aneurysm (AAA) size. The receiver operating characteristic (ROC) curve of plasma MMP-9 levels showed that a cut-off value of 55.18 ng ml(-1) resulted in 100% sensitivity and 96% specificity with an AUC value of 0.988 (P < 0.001) to detect endoleak. CONCLUSIONS: Plasma MMP-9 levels appear to discriminate between patients with and without an endoleak with high sensitivity and specificity.

Genetic parameters for predicted methane production and potential for reducing enteric emissions through genomic selection.

Mitigation of enteric methane (CH4) emission in ruminants has become an important area of research because accumulation of CH4 is linked to global warming. Nutritional and microbial opportunities to reduce CH4 emissions have been extensively researched, but little is known about using natural variation to breed animals with lower CH4 yield. Measuring CH4 emission rates directly from animals is difficult and hinders direct selection on reduced CH4 emission. However, improvements can be made through selection on associated traits (e.g., residual feed intake, RFI) or through selection on CH4 predicted from feed intake and diet composition. The objective was to establish phenotypic and genetic variation in predicted CH4 output, and to determine the potential of genetics to reduce methane emissions in dairy cattle. Experimental data were used and records on daily feed intake, weekly body weights, and weekly milk production were available from 548 heifers. Residual feed intake (MJ/d) is the difference between net energy intake and calculated net energy requirements for maintenance as a function of body weight and for fat- and protein-corrected milk production. Predicted methane emission (PME; g/d) is 6% of gross energy intake (Intergovernmental Panel on Climate Change methodology) corrected for energy content of methane (55.65 kJ/g). The estimated heritabilities for PME and RFI were 0.35 and 0.40, respectively. The positive genetic correlation between RFI and PME indicated that cows with lower RFI have lower PME (estimates ranging from 0.18 to 0.84). Hence, it is possible to decrease the methane production of a cow by selecting more-efficient cows, and the genetic variation suggests that reductions in the order of 11 to 26% in 10 yr are theoretically possible, and could be even higher in a genomic selection program. However, several uncertainties are discussed; for example, the lack of true methane measurements (and the key assumption that methane produced per unit feed is not affected by RFI level), as well as the limitations of predicting the biological consequences of selection. To overcome these limitations, an international effort is required to bring together data on feed intake and methane emissions of dairy cows.

Age of mother and grandmother in relation to a subject's breast cancer risk.

BACKGROUND: On theoretical grounds, the age of the grandmother and the age of the mother at delivery of her daughter may affect the breast cancer risk of the granddaughter. METHODS: We used the data relating to the Diagnostic Research Mamma-carcinoma cohort (DOM (Diagnostisch Onderzoek Mammacarcinoom) 3), which comprises a population-based sample of 12 178 women aged 41-63 years at enrolment in 1982-85 and followed up until 2000. During follow-up 340 postmenopausal breast cancer cases were identified. To these we applied a case-cohort design together with a random sample from the baseline cohort (n=1826). Of these study participants, we were able to retrieve the birth dates of 998 mothers (309 cases, 689 controls), and for 547 of these we also retrieved the birth dates of the grandmothers (197 cases, 350 controls). A weighted Cox proportional hazards model was used to estimate the hazard ratios (HRs) for the effect of the age of the grandmother and the age of the mother on the breast cancer risk of the index women, while adjusting for potential confounders. RESULTS: Compared with the reference group aged 25-29.9 years, the group with the lowest maternal age (<25 years) had an age-adjusted HR of 0.77 (95% CI 0.19-3.12) and the group with the highest maternal age (> or = 40 years) had an age-adjusted HR of 1.58 (95% CI 0.01-267.81), P-value for trend=0.62. Compared with the same reference group, the group with the lowest grandmaternal age (<25 years) had an age-adjusted HR of 0.53 (95% CI 0.24-1.17) and the group with the highest grandmaternal age (> or = 40 years) had an age-adjusted HR of 7.29 (95% CI 1.20-44.46), P for trend=0.04. The associations did not change significantly after additional adjustment for various risk factors for breast cancer, neither for maternal age nor for grandmaternal age. CONCLUSION: This study does not suggest a major role of maternal age at delivery or grandmaternal age at delivery of the mother for the (grand)daughters' breast cancer risk.

SLV330, a cannabinoid CB1 receptor antagonist, ameliorates deficits in the T-maze, object recognition and Social Recognition Tasks in rodents.

Cannabinoid CB(1) receptor (CB(1)R) signaling has been suggested to play an important role in the regulation of memory and cognition. In the present study, our aim was to investigate whether the CB(1)R antagonist SLV330 (doses ranging from 0.3 to 10mg/kg, given orally, p.o.) could ameliorate impairments in distinct aspects of cognition using different disruption models in both mice and rats. Effects of SLV330 were tested on working memory deficits in the T-maze Continuous Alternation Task (T-CAT) in mice; episodic memory deficits in the Object Recognition Task (ORT) and Social Recognition Task (SRT) in rats. The acetylcholinesterase inhibitor (AChEI) donepezil (Aricept, approved for symptomatic treatment of Alzheimer's disease) and nicotine were used as reference compounds. SLV330 markedly improved aging and scopolamine-induced memory deficits in the T-CAT in mice with a lowest effective dose (LED) of 1mg/kg p.o., while reversing the cognitive dysfunction induced by the N-methyl-D-aspartate (NMDA) antagonist dizocilpine (MK-801) only at the middle dose of 3mg/kg. In the ORT, we have found that combined administration of subthreshold doses of SLV330 (1mg/kg, p.o.) and the AChEI donepezil (0.1mg/kg, p.o.), that had no discernable effects on performance when given alone, enhanced memory performance in Wistar rats with deficits induced by the muscarinic antagonist scopolamine, suggestive of additive synergistic effects of SLV330 and donepezil on cognitive impairment. Finally, SLV330 was found to have cognition enhancing properties in a time delay paradigm in the SRT at a LED dose of 3mg/kg (p.o.). In conclusion, the CB(1)R antagonist SLV330 was found to clearly improve memory in several preclinical models for cognitive impairment.

Pre- and postnatal diagnosis and outcome of fetuses and neonates with esophageal atresia and tracheoesophageal fistula.

OBJECTIVES: Clinical symptoms and ultrasound signs during pregnancy could suggest the presence of esophageal atresia (EA). However, most often EA is diagnosed postnatally. The aim of our study is to evaluate the course and outcome for prenatally and postnatally diagnosed EA. In addition, we studied the outcome of isolated versus nonisolated EA. METHODS: In a retrospective data analysis, ultrasound characteristics, maternal and neonatal variables as well as clinical outcome were compared for fetuses/neonates with prenatal (n = 30) or postnatal (n = 49) diagnosis of EA. Clinical outcome in terms of morbidity and mortality of isolated EA was compared with that of EA complicated by chromosomal or structural anomalies. RESULTS: Prenatally diagnosed children were born 2 weeks earlier than postnatally diagnosed children (36.4 weeks vs 38.2 weeks; P = 0.02). The former had higher mortality rates (30 vs 12%; P = 0.05) and more associated anomalies (80 vs 59%; P = 0.04). In both subsets, there was a high morbidity rate in the survivors (not significant). Nonisolated EA was associated with greater occurrence of polyhydramnios (53 vs 27%; P = 0.04) and higher mortality rate (28 vs 0%; P = 0.002). CONCLUSIONS: Mortality was significantly higher in prenatally diagnosed infants and in infants with additional congenital anomalies. Isolated EA is associated with good outcome.

New diagnostic and treatment strategies in renal artery stenosis: a promising pursuit or disappointment foretold?

Clinical management of renal artery stenosis has seen a major shift, after randomised clinical trials have shown no group benefit of endovascular intervention relative to optimal medical control. However, the inclusion criteria of these trials have been criticised for focusing on a subset of patients with atherosclerotic renal artery stenosis where intervention was unlikely to be beneficial. Moreover, new imaging and computational techniques have become available, which have the potential to improve identification of patients that will respond to interventional treatment. This review addresses the challenges associated with clinical decision making in patients with renal artery stenosis. Opportunities for novel diagnostic techniques to improve patient selection are discussed, along with ongoing Dutch studies and network initiatives that investigate these strategies.

The role of AIP variants in pituitary adenomas and concomitant thyroid carcinomas in the Netherlands: a nationwide pathology registry (PALGA) study.

PURPOSE: Germline mutations in the aryl-hydrocarbon receptor interacting protein (AIP) have been identified often in the setting of familial isolated pituitary adenoma (FIPA). To date there is no strong evidence linking germline AIP mutations to other neoplasms apart from the pituitary. Our primary objective was to investigate the prevalence of AIP gene mutations and mutations in genes that have been associated with neuroendocrine tumors in series of tumors from patients presenting with both pituitary adenomas and differentiated thyroid carcinomas (DTCs). METHODS: Pathology samples were retrieved from all pituitary adenomas in patients with concomitant DTCs, including one with a known germline AIP variant. Subsequently, two additional patients with known germline AIP variants were included, of which one presented only with a follicular thyroid carcinoma (FTC). RESULTS: In total, 17 patients (14 DTCs and 15 pituitary adenomas) were investigated by targeted next generation sequencing (NGS). The pituitary tumor samples revealed no mutations, while among the thyroid tumor samples BRAF (6/14, 42.9%) was the most frequently mutated gene, followed by NRAS (3/11, 27.3%). In one AIP-mutated FIPA kindred, the AIP-variant c.853C>T; p.Q285* was confirmed in the FTC specimen, including evidence of loss of heterozygosity (LOH) at the AIP locus in the tumor DNA. CONCLUSION: Although most observed variants in pituitary adenomas and DTCs were similar to those of sporadic DTCs, we confirmed in one AIP mutation-positive case the AIP-variant and LOH at this locus in an FTC specimen, which raises the potential role of the AIP mutation as a rare initiating event.

Prospective evaluation of ischemia in brachial-basilic and forearm prosthetic arteriovenous fistulas for hemodialysis.

UNLABELLED: Ischemia is a devastating complication after arteriovenous fistula (AVF) creation. When not timely corrected, it may lead to amputation. Symptomatic ischemia occurs in 3.7-5% of the hemodialysis population. Upper arm AVFs have a higher incidence of ischemia compared to forearm AVFs. As more patients may need upper arm AVFs in the growing and older hemodialysis population, occurrence of symptomatic ischemia may increase. The purpose of this study is to identify predictors for occurrence of ischemia. METHODS: A prospective evaluation of ischemia was performed in patients randomised for either a brachial-basilic (BB-) AVF or a prosthetic forearm loop AVF. Clinical parameters, preoperative vessel diameters, access flows, digital blood pressures, digit-to-brachial indices (DBI) and interventions for ischemia were recorded. RESULTS: Sixty-one patients (BB-AVF 28) were studied. Seventeen patients (BB-AVF 8) developed ischemic symptoms. Six patients (BB-AVF 3) needed interventions for severe symptoms. Age, history of peripheral arterial reconstruction and radial artery volume flow were significant predictors for the occurrence of ischemia. CONCLUSION: Symptomatic ischemia occurred in 28% of patients with brachial-basilic and prosthetic forearm AVFs. Age, history of peripheral arterial reconstruction and radial artery volume flow might be important for prediction of ischemia.

How do farm models compare when estimating greenhouse gas emissions from dairy cattle production?

The European Union Effort Sharing Regulation (ESR) will require a 30% reduction in greenhouse gas (GHG) emissions by 2030 compared with 2005 from the sectors not included in the European Emissions Trading Scheme, including agriculture. This will require the estimation of current and future emissions from agriculture, including dairy cattle production systems. Using a farm-scale model as part of a Tier 3 method for farm to national scales provides a more holistic and informative approach than IPCC (2006) Tier 2 but requires independent quality control. Comparing the results of using models to simulate a range of scenarios that explore an appropriate range of biophysical and management situations can support this process by providing a framework for placing model results in context. To assess the variation between models and the process of understanding differences, estimates of GHG emissions from four farm-scale models (DairyWise, FarmAC, HolosNor and SFARMMOD) were calculated for eight dairy farming scenarios within a factorial design consisting of two climates (cool/dry and warm/wet)×two soil types (sandy and clayey)×two feeding systems (grass only and grass/maize). The milk yield per cow, follower:cow ratio, manure management system, nitrogen (N) fertilisation and land area were standardised for all scenarios in order to associate the differences in the results with the model structure and function. Potential yield and application of available N in fertiliser and manure were specified separately for grass and maize. Significant differences between models were found in GHG emissions at the farm-scale and for most contributory sources, although there was no difference in the ranking of source magnitudes. The farm-scale GHG emissions, averaged over the four models, was 10.6 t carbon dioxide equivalents (CO2e)/ha per year, with a range of 1.9 t CO2e/ha per year. Even though key production characteristics were specified in the scenarios, there were still significant differences between models in the annual milk production per ha and the amounts of N fertiliser and concentrate feed imported. This was because the models differed in their description of biophysical responses and feedback mechanisms, and in the extent to which management functions were internalised. We conclude that comparing the results of different farm-scale models when applied to a range of scenarios would build confidence in their use in achieving ESR targets, justifying further investment in the development of a wider range of scenarios and software tools.

The association of parental and offspring educational attainment with systolic blood pressure, fasting blood glucose and waist circumference in Latino adults.

OBJECTIVE: The objective of the study is to evaluate the association of intergenerational educational attainment with cardiovascular disease (CVD) risk factors among US Latinos. METHODS: We used cross-sectional data from the Niños Lifestyle and Diabetes Study, an offspring cohort of middle-aged Mexican-Americans whose parents participated in the Sacramento Latino Study on Aging. We collected educational attainment, demographic and health behaviours and measured systolic blood pressure (SBP), fasting glucose and waist circumference. We evaluated the association of parental, offspring and a combined parent-offspring education variable with each CVD risk factor using multivariable regression. RESULTS: Higher parental education was associated only with smaller offspring waist circumference. In contrast, higher offspring education was associated with lower SBP, fasting glucose and smaller waist circumference. Adjustment for parental health behaviours modestly attenuated these offspring associations, whereas adjustment for offspring health behaviours and income attenuated the associations of offspring education with offspring SBP and fasting glucose but not smaller waist circumference, even among offspring with low parental education. CONCLUSIONS: Higher offspring education is associated with lower levels of CVD risk factors in adulthood, despite intergenerational exposure to low parental education.