[Criminal behavior in frontotemporal dementia and Alzheimer's disease]. / Delinquentes Verhalten im Rahmen frontotemporaler Demenzen und der Alzheimer-Erkrankung.

Criminal behavior in older people represents a rare phenomenon. Among older criminals there are many first offenders and 75% are men. Dementia poses one possible origin of delinquency in advanced age. It is unclear how often dementia is the actual cause of delinquency in older age. In studies with older criminals the prevalence of dementia was heterogeneous due to methodological study issues. In the course of the disease 50% of patients with frontotemporal dementia and 10% of patients with Alzheimer's disease commit crimes. The neurobiological origin of delinquency in dementia is poorly understood. On the basis of current study results first delinquency in older age can be explained by impairment of social cognition, difficulties in making appropriate emotional contributions and disturbed control of behavior. Affection of frontal and anterior temporal brain structures seem to be of high relevance. As dementia impairs criminal responsibility psychiatrists are confronted with a forensic evaluation of legal culpability of older criminals. Regarding different etiologies of dementia, specific peculiarities need to be considered in a forensic psychiatric assessment. Especially frontotemporal dementia predisposes towards a wide spectrum of criminal behavior whereas patients with Alzheimer's disease predominantly commit crimes due to cognitive impairment. The review summarizes the present knowledge about criminal behavior in the context of dementia.

A randomized controlled trial on the effect of incomplete milking during the first 5 days in milk on reproductive performance of dairy cows.

The main objective of the current study was to measure the effect of incomplete milking on luteal activity and on pregnancy hazard. We also aimed to study the effect of early-lactation hyperketonemia (i.e., ß-hydroxybutyrate blood concentration ≥1.4 mmol/L during the first 3 wk in milk) on those reproductive outcomes. Multiparous Holstein cows (n = 853) from 13 commercial herds were enrolled in a randomized controlled trial. Cows were assigned to a control or a treatment group, incompletely milked (10-14 L of milk collected/d) from 1 to 5 DIM. Blood samples were collected once a week during weeks in milk 1 to 3 for ß-hydroxybutyrate blood concentration, and a threshold of 1.4 mmol/L was used to define hyperketonemia. During weeks in milk 5 and 7, cows were sampled for progesterone blood concentration, and a threshold of 1 ng/mL was used to define luteal activity. Reproductive information and culling dates were obtained through herd records. Logistic regression models and survival analyses were used to assess the effect of treatment on luteal activity and on pregnancy hazard, respectively. Analogous models were used to investigate the effect of early-lactation hyperketonemia on reproductive outcomes. The odds of luteal activity for incompletely milked cows were 1.1 (95% confidence interval: 0.72-1.7) times those of conventionally milked cows. The effect of treatment on pregnancy hazard varied as a function of time, parity, and start of the breeding period. In second-parity cows that started the breeding period <55 d in milk, the pregnancy hazard (95% confidence interval) in incompletely milked cows was 576.3 (240.0-1,383.7), 36.9 (18.9-72.1), 6.8 (3.3-13.8), 2.5 (1.0-5.9), and 0.13 (0.07-0.26) times that of conventionally milked cows at 1 to 21, 22 to 43, 44 to 65, 66 to 87, and >87 d after the voluntary waiting period, respectively. The treatment did not have an effect on pregnancy hazard in cows in third parity or greater or in those starting the breeding period ≥55 d in milk. Early-lactation hyperketonemia was not associated with any of the reproductive outcomes. In conclusion, the incomplete milking protocol had no effect on luteal activity and had a positive effect on pregnancy hazard in second-parity cows in herds with a short voluntary waiting period (<55 d). We did not observe an effect of early-lactation hyperketonemia on luteal activity or on pregnancy hazard.

Effect of incomplete milking during the first 5 days in milk on udder and reproductive tract health: Results from a randomized controlled trial.

The aim of this study was to investigate the effect of an incomplete milking on risk of mastitis and reproductive tract disease. Multiparous dairy cows (n = 878) from 13 commercial herds were enrolled in a randomized controlled trial. Cows were randomly assigned to either a control (milked conventionally) or a treatment group, which consisted of an incomplete milking (10-14 L of milk collected/d) from 1 to 5 d in milk (DIM). Quarter milk samples were collected at approximately 11 and 18 DIM to measure somatic cell count (SCC). Quarters were considered negative for intramammary infection if SCC was <100,000 cells/mL and positive if SCC was ≥200,000 cells/mL. To calculate intramammary infection incidence, negative quarters of the initial samples collected were tested again 1 wk later. This was done to deter incidence of positive quarters. To calculate elimination rate, positive quarters were tested again 1 wk later to detect mastitis elimination. Farmers recorded clinical mastitis events. Cows were also examined at approximately 35 DIM with a Metricheck device (Simcro, Hamilton, New Zealand) for detection of purulent vaginal discharge (PVD) and with an endometrial cytobrush for presence of leukocytes [endometrial cytology for smear (ENDO) and for leukocyte esterase test (LE)]. A threshold ≥3 was used to define a positive PVD or LE test, whereas a polymorphonuclear cell count ≥6% was used to define a positive ENDO. Five generalized mixed models with cow or herd as random intercepts were used to determine the effects of incomplete milking on odds of new intramammary infection, odds of intramammary infection elimination, and odds of a positive PVD, LE, or ENDO status. To investigate time until first clinical mastitis event, a Cox model with a herd frailty term was used. The odds of new intramammary infection and intramammary infection elimination for incompletely milked cows were 0.90 [95% confidence interval (CI): 0.49, 1.7] and 2.9 (95% CI: 1.4, 6.0) times those of conventionally milked cows, respectively. The hazard of clinical mastitis in incompletely milked cows was 0.96 (95% CI: 0.59, 1.6) times that of conventionally milked cows. The odds of PVD, LE, and ENDO for incompletely milked cows were 1.4 (95% CI: 0.89, 2.1), 1.3 (95% CI: 0.88, 1.8), and 1.2 (95% CI: 0.81, 1.7) times those of conventionally milked cows. These results suggest that incomplete milking during the first 5 DIM increases the odds of a decrease in SCC from 11 to 18 DIM but does not affect odds of increase in SCC in the same period. The incomplete milking had no effect on clinical mastitis incidence in the first 90 DIM or on reproductive tract health at 35 DIM.

A randomized controlled trial on the effect of incomplete milking during early lactation on ketonemia and body condition loss in Holstein dairy cows.

Limiting milk production for a short period of time in early lactation could be a relevant strategy to prevent hyperketonemia (HYK). From December 2013 to March 2015, 838 multiparous Holstein cows from 13 herds were enrolled in a randomized controlled trial evaluating the effect of incomplete milking in early lactation on ketonemia and its effect on body condition score (BCS) loss. Cows were randomly assigned 4 wk before expected calving date to 1 of 2 treatment groups, (1) a conventional milking protocol (CON) for which cows were completely milked or (2) an incomplete milking protocol (INC) for which a maximum of 10 to 14 kg of milk/d were withdrawn during the first 5 d in milk (DIM). ß-Hydroxybutyrate (BHB) concentrations were measured from blood samples collected on each cow 3 times at weekly intervals. Hyperketonemia was defined as BHB ≥1.4 mmol/L. Body condition score variation in the postcalving period was calculated by subtracting BCS assessed at wk 7 from BCS assessed at first week after calving. Effect of treatment on ketonemia and prevalence of HYK were evaluated for 4 specific time periods: 1 to 3, 4 to 7, 8 to 17, and 18 to 26 DIM. Effect of treatment on ketonemia was investigated using linear mixed models with natural logarithm of BHB measurements as outcome and treatment groups as fixed effect. Generalized linear mixed models with HYK as outcome, using logit link, and treatment groups as fixed effect were used to investigate effect of treatment on odds of HYK. A logistic regression model with BCS loss (<0.75 or ≥0.75) as outcome and treatment groups and herd as fixed effects was used to study effect of INC on odds of having BCS loss ≥0.75. A total of 813 lactations had complete data and were used for statistical analysis of ketonemia and HYK. A total of 709 lactations had complete data and were used for analysis of BCS loss. Geometric means of blood BHB concentrations during the 1 to 3, 4 to 7, 8 to 17, and 18 to 26 DIM periods were, respectively, 0.72 (95% confidence interval = 0.66, 0.80), 0.66 (0.60, 0.73), 0.90 (0.80, 1.01), and 0.93 (0.83, 1.05) mmol/L for INC, and 0.65 (0.59, 0.72), 0.79 (0.72, 0.87), 0.94 (0.84, 1.06), and 0.92 (0.82, 1.04) mmol/L for CON. Cows in INC group had lower ketonemia during the 4 to 7 DIM period. Predicted prevalence of HYK during the 1 to 3, 4 to 7, 8 to 17, and 18 to 26 DIM periods were, respectively, 2.8 (3.2, 15.1), 4.6 (2.0, 10.0), 13.4 (8.4, 20.0), and 23.0% (17.4, 29.7) for INC and 2.6 (2.5, 13.8), 10.7 (5.6, 19.3), 19.4 (13.0, 27.9), and 21.3% (16.0, 27.8) for CON. The INC treatment reduced the prevalence of HYK during the 4 to 7 and 8 to 17 DIM periods. No association was observed between INC and BCS loss in the postcalving period. Overall, the incomplete milking protocol was effective for reducing ketonemia and prevalence of HYK during the early postpartum period.

A randomized controlled trial on the effect of incomplete milking during the first 5 days in milk on culling hazard and on milk production and composition of dairy cows.

An incomplete milking in early lactation could help limit negative energy balance in dairy cattle, but its potential effects on culling hazard and on milk production and composition throughout the entire lactation are unknown. The objective of this study was to evaluate the effect of an incomplete milking during the first 5 d in milk on culling hazard, milk weight, milk fat and protein concentrations, and energy-corrected milk (ECM) yield during the whole lactation. A randomized controlled trial was conducted in 13 dairy farms near St-Hyacinthe, Quebec, Canada. Approximately 1 mo before expected calving, Holstein multiparous cows calving between December 2013 and March 2015 (n = 846 cow lactations) were randomly assigned to a control or a treatment group. Cows in the control group were milked conventionally, whereas cows in the treatment group were submitted to an incomplete milking protocol (maximum of 10, 12, and 14 L/d of milk was collected on days in milk 1-3, 4, and 5, respectively). All farms were registered on Dairy Herd Improvement Association, which was used to obtain records on culling, monthly milk yield, and milk fat and protein concentrations. In addition, daily milk yield records were available for 6 farms. A Cox proportional hazards model with a herd frailty term was fitted to the data to compare culling hazard among treatment groups. Regarding milk production and composition, 4 linear mixed models with herd as a fixed effect, cow as a random effect, and using an autoregressive covariance structure were used to study the effect of the incomplete milking on (1) milk weight, (2) milk fat concentration, (3) milk protein concentration, and (4) ECM yield. Culling hazard did not differ among treatment groups (hazard ratio = 1.0; 95% CI = 0.82, 1.3). We observed no differences in milk weight, milk fat, or protein concentration among treatment groups between weeks in milk (WIM) 2 and 44 (the studied period). We noted a difference in ECM between treatment groups for WIM 38, with incompletely milked cows producing less milk than conventionally milked cows (-2.7 kg/d; 95% CI = -0.02, -5.2 kg/d), but no differences were found for any of the other WIM. These results suggest that this strategy for controlling the negative energy balance has negligible effect on cow productivity.

Improving the forecast for biodiversity under climate change.

New biological models are incorporating the realistic processes underlying biological responses to climate change and other human-caused disturbances. However, these more realistic models require detailed information, which is lacking for most species on Earth. Current monitoring efforts mainly document changes in biodiversity, rather than collecting the mechanistic data needed to predict future changes. We describe and prioritize the biological information needed to inform more realistic projections of species' responses to climate change. We also highlight how trait-based approaches and adaptive modeling can leverage sparse data to make broader predictions. We outline a global effort to collect the data necessary to better understand, anticipate, and reduce the damaging effects of climate change on biodiversity.

[Isolation and Characterization of Multipotent Precursor Cells from Murine Adipose Tissue using a Clinically Approved Cell Separation System]. / Isolation und Charakterisierung von multipotenten Vorläuferzellen aus murinem Fettgewebe mithilfe eines klinisch zugelassenen Aufbereitungssystems.

INTRODUCTION: Recent studies underscored the clinical potential of adipose-derived multipotent stem-/precursor cells (ASPCs). One of the main hurdles en route to clinical application was to isolate cells without having to perform expansion cultures outside the OR. A new generation of clinically approved, commercially available cell separation systems claims to provide ASPCs ready for application without further expansion cultures. However, it is unclear if the new systems yield sufficient cells of adequate quality for the use in autologous murine models. The aim of this study was to isolate and characterize adipose-derived precursor cells taken from the inguinal fat pat of wistar rats using InGeneron's clinically approved ARC™-cell separation system. MATERIALS AND METHODS: We isolated cells from the inguinal fat pad of 3 male Wistar rats according to the manufacturer's protocol. In order to reduce the influence of the atmospheric oxygen on the multipotent precursor cells, one half of the cell suspension was cultivated under hypoxia (2% O2) simulating physiological conditions for ASPCs. As a control, the other half of the cells were cultivated under normoxia (21% O2). Cell surface markers CD90, CD29, CD45 and CD11b/c were analyzed by FACS, and osteogenic and adipogenic differentiation of the ASPCs was performed. Finally, cellular growth characteristics were assessed by evaluation of the cumulative population doublings and CFU assay, and metabolic activity was evaluated by WST-1 assay. RESULTS: Processing time was 90 (± 12) min. 1 g of adipose tissue yielded approximately 60 000 plastic adhering cells. Both groups showed a high expression of the mesenchymal stem cell markers CD90 and CD29 while they were negative for the leucocyte markers CD45 and CD11b/c. A strong osteogenic differentiation and a sufficient adipogenic differentiation potential was proven for all ASPCs. Under hypoxia, ASPCs showed increased proliferation characteristics and CFU efficiency as well as a significantly increased metabolic activity. CONCLUSION: This study showed that sufficient multipotent ASPCs of appropriate quality can be isolated from the inguinal fat pad of Wistar rats using the ARC™-cell separation system. As shown in previous studies, cultivation of cells under hypoxic conditions increased their stemness. Our findings will enable future studies that focus on autologous transplantation of ASPCs in a rat model, which most closely resembles a possible clinical application.

Creating a model to detect dairy cattle farms with poor welfare using a national database.

The objective of this study was to determine whether dairy farms with poor cow welfare could be identified using a national database for bovine identification and registration that monitors cattle deaths and movements. The welfare of dairy cattle was assessed using the Welfare Quality(®) protocol (WQ) on 24 Portuguese dairy farms and on 1930 animals. Five farms were classified as having poor welfare and the other 19 were classified as having good welfare. Fourteen million records from the national cattle database were analysed to identify potential welfare indicators for dairy farms. Fifteen potential national welfare indicators were calculated based on that database, and the link between the results on the WQ evaluation and the national cattle database was made using the identification code of each farm. Within the potential national welfare indicators, only two were significantly different between farms with good welfare and poor welfare, 'proportion of on-farm deaths' (p<0.01) and 'female/male birth ratio' (p<0.05). To determine whether the database welfare indicators could be used to distinguish farms with good welfare from farms with poor welfare, we created a model using the classifier J48 of Waikato Environment for Knowledge Analysis. The model was a decision tree based on two variables, 'proportion of on-farm deaths' and 'calving-to-calving interval', and it was able to correctly identify 70% and 79% of the farms classified as having poor and good welfare, respectively. The national cattle database analysis could be useful in helping official veterinary services in detecting farms that have poor welfare and also in determining which welfare indicators are poor on each particular farm.

Transfer of mRNA encoding recombinant immunoreceptors reprograms CD4+ and CD8+ T cells for use in the adoptive immunotherapy of cancer.

Human T lymphocytes can be redirected with a new defined specificity by expression of a chimeric T-cell receptor (immunoreceptor) for the use in adoptive immunotherapy of cancer. Whereas standard procedures use retroviral gene transduction to constitutively express immunoreceptors in T cells, we here explored for the first time mRNA electroporation to achieve transient immunoreceptor expression, and thereby minimizing the risk of persistence of potential autoaggression. CD4(+) and CD8(+) T cells were efficiently transfected with immunoreceptors specific for ErbB2 and CEA. The immunoreceptor expression was transient with half-maximal expression at day 2 and no detectable immunoreceptor expression at day 9 after electroporation. Immunoreceptor-transfected T cells were specifically activated upon coincubation with ErbB2(+) and CEA(+) tumor cells, respectively, resulting in secretion of interferon-gamma (IFNgamma), interleukin-2 (IL-2), and tumor necrosis factor-alpha (TNFalpha). Furthermore, immunoreceptor-transfected CD8(+) T cells specifically lysed ErbB2(+) and CEA(+) tumor cells, respectively. The RNA-transfected T cells retained their cytotoxic function after 2 days of activation and exhibited cytolytic activities like retrovirally transduced T cells. RNA electroporation of T cells thereby provides a versatile tool for transient immunoreceptor expression, which may be of advantage in avoiding the persistence of unintended autoaggression.

Atomic transport and chemical stability during annealing of ultrathin Al2O3 films on Si.

Ultrathin films of Al2O3 deposited on Si were submitted to rapid thermal annealing in vacuum or in oxygen atmosphere, in the temperature range from 600 to 800 degrees C. Nuclear reaction profiling with subnanometric depth resolution evidenced mobility of O, Al, and Si species, and angle-resolved x-ray photoelectron spectroscopy revealed the formation of Si-Al-O compounds in near-surface regions, under oxidizing atmosphere at and above 700 degrees C. Under vacuum annealing all species remained essentially immobile. A model is presented based on diffusion-reaction equations capable of explaining the mobilities and reproducing the obtained profiles.

[Endoscopic treatment of intervertebral disk displacement. Percutaneous transforaminal access to the epidural space. Indications, technique and initial results]. / Endoskopische Behandlung sequestrieter Bandscheibenvorfälle. Der perkutane transforaminale Zugang zum Epiduralraum. Indikationen, Technik und erste Ergebnisse.

The authors report their experiences with the percutaneous transforaminal approach to the epidural space. 85 patients were treated endoscopically for non-contained lumbar herniated discs. Very good and good results of 20 patients (learning curve) were obtained in 65%. However, reoperation rate was 25% versus 3% for the last 65 patients. The first 50 patients were treated under local anaesthesia, the last 35 patients under general anaesthesia. Operative technique is described in detail. Laser application in the epidural space is helpful for tissue ablation and to obtain hemostasis. No complications were observed. The main advantages of this new minimal invasive technique are, besides reduced morbidity, less epidural scarring and removal of the sequestered tissue under visual control while retaining disc tissue in the intervertebral space. Thus, the disadvantages of open nucleotomy with possible instability and abundant scarring may be avoided.

[Endoscopic prosthesis implantation in stenoses and fistulas of the proximal cervical esophagus]. / Endoskopische Prothesenimplantation bei Stenosen und Fisteln der proximalen zervikalen Speiseröhre.

Endoscopic placement of an esophageal prosthesis is a well established palliative treatment for esophageal carcinoma. However, the treatment of high cervical tumors using commercially available plastic prostheses is problematic. We modified the design and implantation techniques of the Celestin prosthesis to accommodate high cervical tumors and report our results in 38 patients. Over a 7 year period 42 modified Celestin prostheses were implanted in 38 patients with high cervical esophageal tumors. 15 had stenosis only, 22 had a stenosis and fistula, and one had a fistula without stenosis. Graduated bouginage up to 38 Fr or 42 Fr for large prostheses was performed prior to stent placement in an average of 2.3 sessions. There were no procedure-related complications. Only in one case the prosthesis had to be withdrawn after reimplantation because of intolerable painful foreign body sensation. Improvement of dysphagia was achieved in 34 patients. The fistulas could be adequately bridged and sealed in 17 of 23 patients. Prostheses migrated in 11 cases (proximally, n = 6; distally, n = 5). Mean patient survival in 28 patients followed until death was 86 days (range 5-338 days).

Mobilization of cognitive resources and the generation effect.

The generation effect refers to the memory advantage of words that have been generated rather than read. Such a read-generate comparison confounds qualitative task differences and raises methodological problems. A revised methodology is proposed circumventing these problems in that the encoding task is held constant and all stimuli have to be generated, but the degree of generativeness (i.e. the amount of cueing) is varied. In Experiment 1, 1, the (refined version of the) generation effect is demonstrated in a within-subjects design; with increasing generation activity left to the subject, free recall performance increases. No effect is obtained for degree of target masking. The same finding is replicated and shown to be independent of self-paced study time when generative activity is manipulated between subjects (Experiment 2) or within subjects (Experiment 3). As all learning trials involve generation, encoding time is controlled statistically, and free recall is used as a measure of memory, this refined generation effect cannot be explained as an artifact of selective attention or elaboration. Rather, generative activity seems to increase the mobilization of cognitive resources. This motivational account is supported by Experiment 4 showing an enhanced generation effect for positive mood.

[Effect and side effects of oral morphine, lormetazepam and placebos as premedication]. / Die Wirkung und Nebenwirkung oralen Morphins, Lormetazepams und Plazebos zur Prämedikation.

In 60 patients undergoing a curettage in thiopentone induced inhalation anaesthesia with enflurane and N2O/O2 = 2:1, the effects of oral premedication (2 h before anaesthesia) with 30 mg morphine (MST 30) (n = 21), 1 mg lormetazepam (Noctamid) (n = 19) and placebo (n = 21) on psychological (anxiety, depression and asthenia), physiological (blood pressure, heart and respiratory rate) and pain parameters (visual analogue scale, analgesic consumption) were investigated. The study design was single blind, randomized. Before premedication the three groups did not differ in one parameter and so were comparable. MST 30 had a significantly better anxiolytic, Lormetazepam a significantly better antidepressive effect than the compared substance. There were no differences in blood pressure and heart rate. In contrast to lormetazepam and placebo after MST 30 there was no increase in the respiratory rate which can be explained by the anxiolytic stress reducing effect. There was no difference in peri- and intraoperative pain parameters, probably due to the type of surgery. Nausea and vomiting occurred more frequently after MST 30, but there was no significance. A higher rate was probably prevented by the application of transdermal scopolamine the day before surgery. The indication of analgesics (opiates) for premedication is discussed taking the controversy into account. The results of this study show that oral morphine (MST 30) has an anxiolytic effect, one of the most important effects a premedication should have. Further studies should investigate in which types of surgery the analgesic effect of MST 30 is peri- and intraoperatively relevant, so that advantages compared to e.g. Flunitrazepam, Midazolam or Lormetazepam in a higher dosage could be expected.

Regulation of rates of lipolysis in isolated myocardial cells from rat heart.

Rates of lipolysis in isolated myocardial cells (myocytes) from rat heart, as measured by the release of glycerol and a reduction in endogenous triacylglycerols, can be stimulated by isoproterenol. Myocyte preparations were calcium-tolerant and were quiescent, even in the presence of isoproterenol, so the stimulation of lipolysis by isoproterenol cannot be secondary to a physiological (inotropic) response. N6-Phenylisopropyladenosine did not reduce isoproterenol-stimulated rates of lipolysis. Increasing the calcium concentration in the incubation medium from 0.75 to 3 mM did not increase the basal output of glycerol. Furthermore, incubation of calcium-tolerant myocytes in the absence of calcium had no effect on either basal or isoproterenol-stimulated rates of lipolysis. Therefore, calcium ions must not influence the lipolytic process directly, and so the calcium dependency for lipolysis observed with perfused heart preparations must reflect the effect of calcium on the contractile performance of the heart, which only secondarily produced a change in rates of lipolysis.