Heritability, determinants and reference values of renal length: a family-based population study.

OBJECTIVES: In this population-based study, reference values were generated for renal length, and the heritability and factors associated with kidney length were assessed. METHODS: Anthropometric parameters and renal ultrasound measurements were assessed in randomly selected nuclear families of European ancestry (Switzerland). The adjusted narrow sense heritability of kidney size parameters was estimated by maximum likelihood assuming multivariate normality after power transformation. Gender-specific reference centiles were generated for renal length according to body height in the subset of non-diabetic non-obese participants with normal renal function. RESULTS: We included 374 men and 419 women (mean ± SD, age 47 ± 18 and 48 ± 17 years, BMI 26.2 ± 4 and 24.5 ± 5 kg/m(2), respectively) from 205 families. Renal length was 11.4 ± 0.8 cm in men and 10.7 ± 0.8 cm in women; there was no difference between right and left renal length. Body height, weight and estimated glomerular filtration rate (eGFR) were positively associated with renal length, kidney function negatively, age quadratically, whereas gender and hypertension were not. The adjusted heritability estimates of renal length and volume were 47.3 ± 8.5 % and 45.5 ± 8.8 %, respectively (P < 0.001). CONCLUSION: The significant heritability of renal length and volume highlights the familial aggregation of this trait, independently of age and body size. Population-based references for renal length provide a useful guide for clinicians. KEY POINTS: • Renal length and volume are heritable traits, independent of age and size. • Based on a European population, gender-specific reference values/percentiles are provided for renal length. • Renal length correlates positively with body length and weight. • There was no difference between right and left renal lengths in this study. • This negates general teaching that the left kidney is larger and longer.

Synthesis of medium-chain-length polyhydroxyalkanoates in arabidopsis thaliana using intermediates of peroxisomal fatty acid beta-oxidation.

Polyhydroxyalkanoate (PHA) is a family of polymers composed primarily of R-3-hydroxyalkanoic acids. These polymers have properties of biodegradable thermoplastics and elastomers. Medium-chain-length PHAs (MCL-PHAs) are synthesized in bacteria by using intermediates of the beta-oxidation of alkanoic acids. To assess the feasibility of producing MCL-PHAs in plants, Arabidopsis thaliana was transformed with the PhaC1 synthase from Pseudomonas aeruginosa modified for peroxisome targeting by addition of the carboxyl 34 amino acids from the Brassica napus isocitrate lyase. Immunocytochemistry demonstrated that the modified PHA synthase was appropriately targeted to leaf-type peroxisomes in light-grown plants and glyoxysomes in dark-grown plants. Plants expressing the PHA synthase accumulated electron-lucent inclusions in the glyoxysomes and leaf-type peroxisomes, as well as in the vacuole. These inclusions were similar to bacterial PHA inclusions. Analysis of plant extracts by GC and mass spectrometry demonstrated the presence of MCL-PHA in transgenic plants to approximately 4 mg per g of dry weight. The plant PHA contained saturated and unsaturated 3-hydroxyalkanoic acids ranging from six to 16 carbons with 41% of the monomers being 3-hydroxyoctanoic acid and 3-hydroxyoctenoic acid. These results indicate that the beta-oxidation of plant fatty acids can generate a broad range of R-3-hydroxyacyl-CoA intermediates that can be used to synthesize MCL-PHAs.

Angiotensin II favors progression to heart failure in diabetic hearts: role of myocardial fatty acid oxidation downregulation

Purpose: Diabetic myocardium is particularly vulnerable to develop heart failure in response to chronic stress conditions including hypertension or myocardial infarction. We have recently observed that angiotensin II (Ang II)-mediated downregulation of the fatty acid oxidation pathway favors occurrence of heart failure by myocardial accumulation of lipids (lipotoxicity). Because diabetic heart is exposed to high levels of circulating fatty acid, we determined whether insulin resistance favors development of heart failure in mice with Ang II-mediated myocardial remodeling.Methods: To study the combined effect of diabetes and Ang II-induced heart remodeling, we generated leptin-deficient/insulin resistant (Lepob/ob) mice with cardiac targeted overexpression of angiotensinogen (TGAOGN). Left ventricular (LV) failure was indicated by pulmonary congestion (lung weight/tibial length>+2SD of wild-type mice). Myocardial metabolism and function were assessed during in vitro isolated working heart perfusion.Results: Forty-eight percent of TGAOGN mice without insulin resistance exhibited pulmonary congestion at the age of 6 months associated with increased myocardial BNP expression (+375% compared with WT) and reduced LV power (developed pressure x cardiac output; -15%). The proportion of mice presenting heart failure was markedly increased to 71% in TGAOGN mice with insulin resistance (TGAOGN/Lepob/ob). TGAOGN/Lepob/ob mice with heart failure exhibited further increase of BNP compared with failing non-diabetic TGAOGN mice (+146%) and further reduction of cardiac power (-59%). Mice with insulin resistance alone (Lepob/ob) did not exhibit signs of heart failure or LV dysfunction. Myocardial fatty acid oxidation measured during in vitro perfusion was markedly increased in non-failing hearts from Lepob/ob mice (+380% compared with WT) and glucose oxidation decreased (-72%). In contrast, fatty acid and glucose oxidation did not differ from Lepob/ob mice in hearts from TGAOGN/Lepob/ob mice without heart failure. However, both fatty acid and glucose oxidation were markedly decreased (-47% and -48%, respectively, compared with WT/Lepob/+) in failing hearts from TGAOGN/Lepob/ob mice. Reduction of fatty acid oxidation was associated with marked reduction of protein expression of a number of regulatory enzymes implied in fatty acid oxidation.Conclusions: Insulin resistance favors the progression to heart failure during chronic exposure of the myocardium to Ang II. Our results are compatible with a role of Ang II-mediated downregulation of fatty acid oxidation, potentially promoting lipotoxicity.

Genetic diversity and differentiation processes in the ploidy series of Olea europaea L.: a multiscale approach from subspecies to insular populations.

Geographical isolation and polyploidization are central concepts in plant evolution. The hierarchical organization of archipelagos in this study provides a framework for testing the evolutionary consequences for polyploid taxa and populations occurring in isolation. Using amplified fragment length polymorphism and simple sequence repeat markers, we determined the genetic diversity and differentiation patterns at three levels of geographical isolation in Olea europaea: mainland-archipelagos, islands within an archipelago, and populations within an island. At the subspecies scale, the hexaploid ssp. maroccana (southwest Morocco) exhibited higher genetic diversity than the insular counterparts. In contrast, the tetraploid ssp. cerasiformis (Madeira) displayed values similar to those obtained for the diploid ssp. guanchica (Canary Islands). Geographical isolation was associated with a high genetic differentiation at this scale. In the Canarian archipelago, the stepping-stone model of differentiation suggested in a previous study was partially supported. Within the western lineage, an east-to-west differentiation pattern was confirmed. Conversely, the easternmost populations were more related to the mainland ssp. europaea than to the western guanchica lineage. Genetic diversity across the Canarian archipelago was significantly correlated with the date of the last volcanic activity in the area/island where each population occurs. At the island scale, this pattern was not confirmed in older islands (Tenerife and Madeira), where populations were genetically homogeneous. In contrast, founder effects resulted in low genetic diversity and marked genetic differentiation among populations of the youngest island, La Palma.

Emergency department use by oldest-old patients from 2005 to 2010 in a Swiss university hospital.

BACKGROUND: Aging of the population in all western countries will challenge Emergency Departments (ED) as old patients visit these health services more frequently and present with special needs. The aim of this study is to describe the trend in ED visits by patients aged 85 years and over between 2005 and 2010, and to compare their service use to that of patients aged 65-84 years during this period and to investigate the evolution of these comparisons over time. METHODS: Data considered were all ED visits to the University of Lausanne Medical Center (CHUV), a tertiary Swiss teaching hospital, between 2005 and 2010 by patients aged 65 years and over (65+ years). ED visit characteristics were described according to age group and year. Incidence rates of ED visits and length of ED stay were calculated. RESULTS: Between 2005 and 2010, ED visits by patients aged 65 years and over increased by 26% overall, and by 46% among those aged 85 years and over (85+ years). Estimated ED visit incidence rate for persons aged 85+ years old was twice as high as for persons aged 65-84 years. Compared to patients aged 65-84 years, those aged 85+ years were more likely to be hospitalized and have a longer ED stay. This latter difference increased over time between 2005 and 2010. CONCLUSIONS: Oldest-old patients are increasingly using ED services. These services need to adapt their care delivery processes to meet the needs of a rising number of these complex, multimorbid and vulnerable patients.

Male dominance linked to size and age, but not to 'good genes' in brown trout (Salmo trutta).

BACKGROUND: Males that are successful in intra-sexual competition are often assumed to be of superior quality. In the mating system of most salmonid species, intensive dominance fights are common and the winners monopolise most mates and sire most offspring. We drew a random sample of mature male brown trout (Salmo trutta) from two wild populations and determined their dominance hierarchy or traits linked to dominance. The fish were then stripped and their sperm was used for in vitro fertilisations in two full-factorial breeding designs. We recorded embryo viability until hatching in both experiments, and juvenile survival during 20 months after release into a natural streamlet in the second experiment. Since offspring of brown trout get only genes from their fathers, we used offspring survival as a quality measure to test (i) whether males differ in their genetic quality, and if so, (ii) whether dominance or traits linked to dominance reveal 'good genes'. RESULTS: We found significant additive genetic variance on embryo survival, i.e. males differed in their genetic quality. Older, heavier and larger males were more successful in intra-sexual selection. However, neither dominance nor dominance indicators like body length, weight or age were significantly linked to genetic quality measured as embryo or juvenile survival. CONCLUSION: We found no evidence that females can improve their offspring's genetic viability by mating with large and dominant males. If there still were advantages of mating with dominant males, they may be linked to non-genetic benefits or to genetic advantages that are context dependent and therefore possibly not revealed under our experimental conditions - even if we found significant additive genetic variation for embryo viability under such conditions.

Species identification in mammals from mixed biological samples based on mitochondrial DNA control region length polymorphism.

The ability to identify the species origin of an unknown biological sample is relevant in the fields of human and wildlife forensics. However, the detection of several species mixed in the same sample still remains a challenge. We developed and tested a new approach for mammal DNA identification in mixtures of two or three species, based on the analysis of mitochondrial DNA control region interspecific length polymorphism followed by direct sequencing. Contrary to other published methods dealing with species mixtures, our protocol requires a single universal primer pair and is not based on a pre-defined panel of species. Amplicons can be separated either on agarose gels or using CE. The advantages and limitations of the assay are discussed under different conditions, such as variable template concentration, amplicon sizes and size difference among the amplicons present in the mixture. For the first time, this protocol provides a simple, reliable and flexible method for simultaneous identification of multiple mammalian species from mixtures, without any prior knowledge of the species involved.

Transitions in social complexity along elevational gradients reveal a combined impact of season length and development time on social evolution.

Eusociality is taxonomically rare, yet associated with great ecological success. Surprisingly, studies of environmental conditions favouring eusociality are often contradictory. Harsh conditions associated with increasing altitude and latitude seem to favour increased sociality in bumblebees and ants, but the reverse pattern is found in halictid bees and polistine wasps. Here, we compare the life histories and distributions of populations of 176 species of Hymenoptera from the Swiss Alps. We show that differences in altitudinal distributions and development times among social forms can explain these contrasting patterns: highly social taxa develop more quickly than intermediate social taxa, and are thus able to complete the reproductive cycle in shorter seasons at higher elevations. This dual impact of altitude and development time on sociality illustrates that ecological constraints can elicit dynamic shifts in behaviour, and helps explain the complex distribution of sociality across ecological gradients.

A measure of the intensity of response to alcohol to screen for alcohol use disorders in primary care.

Alcohol-dependent subjects tend to report lower level of response to alcohol (LR) in the years before the disorder developed, compared to control subjects. The Self-Rating of the Effects of alcohol (SRE) score is a quick and valid retrospective estimate of LR. This study examined the associations between alcohol abuse or dependence and early experience of alcohol as measured on retrospective SRE score (relating to the first five times alcohol was imbibed), and the presence of alcohol abuse or dependence, in patients attending primary care. Higher Early SRE score (i.e. greater early tolerance of alcohol) was obtained in patients with an alcohol-related diagnosis than in patients without those diagnoses. Using a cut-off of 2 on the Early SRE score, the Early SRE score could discriminate between patients with and without an alcohol diagnosis with moderate to high sensitivity (84%) and modest specificity (57%).

Is the absence of spiritual well-being at the facit-sp equivalent to spiritual distress in older patients?

Objective: Although initially developed to assess spiritual well-being,the FACIT-Sp is increasingly used to assess the other end of the spectrum,i.e. spiritual distress. This study intends to investigate whether theFACIT-Sp could really contribute to this aim in older patients. Method:Patients (N=135, 81.47.1 years, 68.3% women) aged 65 years and over,with MMSE score>19, admitted consecutively in post-acute rehabilitationwere enrolled. The FACIT-Sp (12 items, score 0 to 48, high spiritualwell-being defined as score_36) was administered and commentswere systematically retrieved. Results: Overall, 32(23.7%) patients hadhigh spiritual well-being. FACIT-Sp internal consistency was good(Cronbach's 0.85) and a confirmatory factorial analysis was consistentwith Meaning and Faith proposed subscales. Qualitative analysisshowed that negative answers (score=0) to "My illness has strengthenedmy faith or spiritual beliefs" (N=76/135) could equally reflect theabsence of impact (49/76, 64.5%) or a negative impact (religious struggle,27/76, 35.5%) of illness on faith. However, former patients had significantlyhigher FACIT-Sp scores than the latter (30.35.6 vs 20.97.9,P<.001). Similarly, among patients (N=73/135) with negative answers(score<3) to "I feel a sense of purpose in my life" those mentioning their"old age" to explain their answer (N=34/73, 46.6%) had higher FACITSpscores than those who did not (26.47.7 vs 22.58.1,P=.02). Conclusion:The FACIT-Sp identifies older people with high spiritual wellbeingbut could underestimate well-being in some older patients. Lowscores on some items could have very different meanings and interpretationof FACIT-Sp global scores below the usual cut-off should becautious.

Warming experiments underpredict plant phenological responses to climate change.

Warming experiments are increasingly relied on to estimate plant responses to global climate change. For experiments to provide meaningful predictions of future responses, they should reflect the empirical record of responses to temperature variability and recent warming, including advances in the timing of flowering and leafing. We compared phenology (the timing of recurring life history events) in observational studies and warming experiments spanning four continents and 1,634 plant species using a common measure of temperature sensitivity (change in days per degree Celsius). We show that warming experiments underpredict advances in the timing of flowering and leafing by 8.5-fold and 4.0-fold, respectively, compared with long-term observations. For species that were common to both study types, the experimental results did not match the observational data in sign or magnitude. The observational data also showed that species that flower earliest in the spring have the highest temperature sensitivities, but this trend was not reflected in the experimental data. These significant mismatches seem to be unrelated to the study length or to the degree of manipulated warming in experiments. The discrepancy between experiments and observations, however, could arise from complex interactions among multiple drivers in the observational data, or it could arise from remediable artefacts in the experiments that result in lower irradiance and drier soils, thus dampening the phenological responses to manipulated warming. Our results introduce uncertainty into ecosystem models that are informed solely by experiments and suggest that responses to climate change that are predicted using such models should be re-evaluated.

Could Hyperglycaemia and Troponin I predict outcome in intensive care after congenital heart surgery in children?

Objective: To establish if hyperglycaemia and cardiac Troponin I (cTnI) after congenital heart surgery on cardiopulmonary bypass in children could predict outcome in intensive care unit. Methods: retrospective cohort study including 274 children (mean age 4.6 years; range 0 - 17 years-old). CTnI and glucose values were retrieved from our database. Integrated values (area under the curve (AUC)) were calculated for evaluation of sustained hyperglycaemia and then normalised per hour (48h-Gluc/h). Maximal cTnI, fi rst glucose value (Gluc1) and 48h-Gluc/h were then correlated with duration of mechanical ventilation, ICU stay and mortality using cut-off values. Results: The mean duration of mechanical ventilation was 5.1 ± 7.2 days and ICU stay was 11.0 ± 13.3 days, 11 patients (3.9%) died. Hyperglycaemia (>6.1 mmol/l) was present in 68% of children at admission and was sustained in 85% for 48 hours. The mean value of Gluc1 (7.3 ± 2.7 vs. 11.8 ± 6.4 mmol/l, p < 0.0001), 48h-Gluc/h (7.4 ± 1.4 vs. 9.9 ± 4.6 mmol/l/h, p < 0.0001) and cTnI max (16.7 ± 21.8 vs. 59.2 ± 41.4 mcg/l, p < 0.0001) were signifi cantly lower in survivors vs. non survivors. Cut-off values and odds ratio are summarised in Table 1. Analyses for duration of mechanical ventilation and for length of stay in ICU are depicted in Table 2. Conclusions: Hyperglycaemia is frequent after cardiopulmonary bypass and sustained in the fi rst 48 hours. Admission glycaemia and cTnI max are associated with a high risk of mortality, prolonged duration of mechanical ventilation and prolonged length of stay in ICU.

Semi-supervised segmentation of ultrasound images based on patch representation and continuous min cut.

Ultrasound segmentation is a challenging problem due to the inherent speckle and some artifacts like shadows, attenuation and signal dropout. Existing methods need to include strong priors like shape priors or analytical intensity models to succeed in the segmentation. However, such priors tend to limit these methods to a specific target or imaging settings, and they are not always applicable to pathological cases. This work introduces a semi-supervised segmentation framework for ultrasound imaging that alleviates the limitation of fully automatic segmentation, that is, it is applicable to any kind of target and imaging settings. Our methodology uses a graph of image patches to represent the ultrasound image and user-assisted initialization with labels, which acts as soft priors. The segmentation problem is formulated as a continuous minimum cut problem and solved with an efficient optimization algorithm. We validate our segmentation framework on clinical ultrasound imaging (prostate, fetus, and tumors of the liver and eye). We obtain high similarity agreement with the ground truth provided by medical expert delineations in all applications (94% DICE values in average) and the proposed algorithm performs favorably with the literature.

Does history of falling predict length of stay in post-scute geriatric rehabilitation?

Objectives: To investigate the associations between falls before¦hospital admission, falls during hospitalization, and length of stay in¦elderly people admitted to post-acute geriatric rehabilitation.¦Method: History of falling in the previous 12 months before admission¦was recorded among 249 older persons (mean age 82.3 ± 7.4 years,¦69.1% women) consecutively admitted to post-acute rehabilitation. Data¦on medical, functional and cognitive status were collected upon¦admission. Falls during hospitalization and length of stay were recorded¦at discharge.¦Results: Overall, 92 (40.4%) patients reported no fall in the 12 months¦before admission; 63(27.6%) reported 1 fall, and 73 (32.0%) reported¦multiple falls. Previous falls occurrence (one or more falls) was¦significantly associated with in-stay falls (19.9% of previous fallers fell¦during the stay vs 7.6% in patients without history of falling, P = .01),¦and with a longer length of stay (22.4 ± 10.1 days vs 27.1 ± 14.3 days,¦P = .01). In multivariate robust regression controlling for gender, age,¦functional and cognitive status, history of falling remained significantly¦associated with longer rehabilitation stay (2.8 days more than non¦fallers in single fallers, p = .05, and 3.3 days in multiple fallers, p = .0.1).¦Conclusion: History of falling in the 12 months prior to post acute¦geriatric rehabilitation is independently associated with a longer¦rehabilitation length of stay. Previous fallers also have an increased risk¦of falling during rehabilitation stay. This suggests that hospital fall¦prevention measures should particularly target these high risk patients.

Major depressive disorders in the general hospital: how to implement guidelines.

OBJECTIVE: An implementation study that evaluated the impact of previously adopted guidelines on the clinical practice of medical residents was conducted to improve the recognition and treatment of major depressive disorders (MDDs) in hospitalized patients with somatic diseases. METHODS: Guidelines were implemented in two wards (ENT and oncology) using intranet diffusion, interactive sessions with medical residents, and support material. Discharge letters of 337 and 325 patients, before and after the intervention, respectively, were checked for statement of diagnosis or treatment of MDDs and, in a post hoc analysis, for any mention about psychiatric management. RESULTS: No difference was found in the number of diagnosed or treated MDDs before and after the intervention. However, significantly more statements about psychological status (29/309 vs. 13/327) and its management (36/309 vs. 19/327) were observed after the intervention (P<.01). CONCLUSION: The intervention was not successful in improving the management of MDDs. However, a possible effect on general psychological aspects of medical diseases was observed.