Risk of hospitalization and death following prostate biopsy in Scotland

AbstractObjectiveTo investigate the risk of hospitalization and death following prostate biopsy.Study designRetrospective cohort study.MethodsOur study population comprised 10,285 patients with a record of first ever prostate biopsy between 2009 and 2013 on computerized acute hospital discharge or outpatient records covering Scotland. Using the general population as a comparison group, expected numbers of admissions/deaths were derived by applying age-, sex-, deprivation category-, and calendar year-specific rates of hospital admissions/deaths to the study population. Indirectly standardized hospital admission ratios (SHRs) and mortality ratios (SMRs) were calculated by dividing the observed numbers of admissions/deaths by expected numbers.ResultsCompared with background rates, patients were more likely to be admitted to hospital within 30 days (SHR 2.7; 95% confidence interval 2.4, 2.9) and 120 days (SHR 4.0; 3.8, 4.1) of biopsy. Patients with prior co-morbidity had higher SHRs. The risk of death within 30 days of biopsy was not increased significantly (SMR 1.6; 0.9, 2.7), but within 120 days, the risk of death was significantly higher than expected (SMR 1.9; 1.5, 2.4). The risk of death increased with age and tended to be higher among patients with prior co-morbidity. Overall risks of hospitalization and of death up to 120 days were increased both in men diagnosed and those not diagnosed with prostate cancer.ConclusionsHigher rates of adverse events in older patients and patients with prior co-morbidity emphasizes the need for careful patient selection for prostate biopsy and justifies ongoing efforts to minimize the risk of complications

Lena Delta hydrology and geochemistry: long-term hydrological data and recent field observations

The Lena River forms one of the largest deltas in the Arctic. We compare two sets of data to reveal new insights into the hydrological, hydrochemical, and geochemical processes within the delta: (i) long-term hydrometric observations at the Khabarova station at the head of the delta from 1951 to 2005; (ii) field hydrological and geochemical observations carried out within the delta since 2002. Periods with differing relative discharge and intensity of fluvial processes were identified from the long-term record of water and sediment discharge. Ice events during spring melt (high water) reconfigured branch channels and probably influenced sediment transport within the delta. Based on summer field measurements during 2005–2012 of discharge and sediment fluxes along main delta channels, both are increased between the apex and the front of the delta. This increase is to a great extent connected with an additional influx of water from tributaries, as well as an increase of suspended and dissolved material released from the ice complex. Summer concentrations of major ion and biogenic substances along the delta branches are partly explained by water sources within the delta, such as thawing ice complex waters, small Lena River branches and estuarine areas

Synergistic control of transmitter turnover at glycinergic synapses by GlyT1, GlyT2, and ASC-1

In addition to being involved in protein biosynthesis and metabolism, the amino acid glycine is the most important inhibitory neurotransmitter in caudal regions of the brain. These functions require a tight regulation of glycine concentration not only in the synaptic cleft, but also in various intracellular and extracellular compartments. This is achieved not only by confining the synthesis and degradation of glycine predominantly to the mitochondria, but also by the action of high-affinity large-capacity glycine transporters that mediate the transport of glycine across the membranes of presynaptic terminals or glial cells surrounding the synapses. Although most cells at glycine-dependent synapses express more than one transporter with high affinity for glycine, their synergistic functional interaction is only poorly understood. In this review, we summarize our current knowledge of the two high-affinity transporters for glycine, the sodium-dependent glycine transporters 1 (GlyT1; SLC6A9) and 2 (GlyT2; SLC6A5) and the alanine–serine–cysteine-1 transporter (Asc-1; SLC7A10)

Results-Based Bilateral Development Cooperation: The triad of country strategy - (development cooperation) programme - module

In recent years, Germany's Federal Ministry for Economic Cooperation and Development (BMZ) has launched fundamental reforms. These are designed to enable bilateral official development cooperation to make a more targeted and effective contribution towards implementing the 2030 Agenda and the Paris Agreement. Reform processes such as 'BMZ 2030' and the joint procedural reform are important steps in this regard. In its report on the results orientation and evaluability of development cooperation programmes, DEval delivers initial findings on the application of the new procedures and requirements under the joint procedural reform, and their effects. This policy brief summarises the key findings of this evaluation

What Do We Know About the Effects of Private Sector Engagement?

Development cooperation has created a range of instruments to support private companies wishing to invest in partner countries whilst also pursuing development goals. These instruments are primarily expected to mobilise the additional funding needed to finance the Sustainable Development Goals (SDGs). But as to how far private sector engagement is achieving this and other objectives, until now the only research has taken the form of evaluations and academic studies on individual projects and instruments. In the evaluation synthesis by DEval (Habbel et al., 2021) the available evidence on private sector engagement is analysed systematically for the first time. This policy brief summarises the most important findings and recommendations from the evaluation synthesis by DEval

Progression and Death as Competing Risks in Ovarian Cancer

Background: Progression of a cancer disease and dying without progression can be understood as competing risks. The Cause-Specific Hazards Model and the Fine and Gray model on cumulative incidences are common statistical models to handle this problem. The pseudo value approach by Andersen and Klein is also able to cope with competing risks. It is still unclear which model suits best in which situation.Methods: For a simulated dataset and a real data example of ovarian cancer patients who are exposed to progression and death the three models are examined. We compare the three models with regards to interpretation and modeling requirements.Results: In this study, the parameter estimates for the competing risks are similar from the Cause-Specific Hazards Model and the Fine and Gray model. The pseudo value approach yields divergent results which are heavily dependent on modeling details.Conclusions: The investigated approaches do not exclude each other but moreover complement one another. The pseudo value approach is an alternative that circumvents proportionality assumptions. As in all survival analyses, situations with low event rates should be interpreted carefully

Die Nachwuchsgeneration der deutschen Industrie zwischen Karriere, Kulturen und Bildung: eine qualitative Studie zu Karriereverhalten und Auslandsentsendung untersucht am Beispiel des Rückkehr- und Wiedereingliederungsverhaltens unter Berücksichtigung generationsspezifischer Merkmale

Diese Dissertation geht qualitativ-empirisch der Frage der ständig steigenden Bedeutung der Internationalisierung der Wirtschaft und Industrie nach. Untersucht wurde am Beispiel eines deutschen Konzerns, welchen Stellenwert die Auslandsentsendung von Mitarbeitern hat, konkret am Rückkehr- und Wiedereingliederungsverhalten unter Berücksichtigung generationsspezifischer und biographietypischer Merkmale. Objektiv-hermeneutisch ausgewertete Einzelinterviews mit aus dem Ausland heimkehrenden Mitarbeitern (ca. 30 Jahre alt) ergab folgende Ergebnisse: Die generationsspezifische Frage 'Wer kehrt aus dem Ausland zurück?' führte zum Bild der Nachwuchsgeneration der Wirtschaft (Idealtypologie). Bezüglich der Rückkehr konnten drei Haltungen im Umgang mit dem Wiedereingliederungsprozess festgestellt werden, sowie drei Haltungen in der rückblickenden Selbsteinschätzung der Entsendung. Die Ergebnisse der vorliegenden Untersuchung sind auf drei Ebenen relevant: auf der Ebene des konkreten, unternehmerischen Alltags (Auslandsentsendung und Nachwuchsgeneration), auf der pädagogischen Ebene (neues Bildungsverständnis) und auf der sozialwissenschaftlichen Ebene (Nachwuchsgeneration)

Inspiratory off-switch mediated by optogenetic activation of inhibitory neurons in the preBötzinger complex in vivo

The role of inhibitory neurons in the respiratory network is a matter of ongoing debate. Conflicting and contradicting results are manifold and the question whether inhibitory neurons are essential for the generation of the respiratory rhythm as such is controversial. Inhibitory neurons are required in pulmonary reflexes for adapting the activity of the central respiratory network to the status of the lung and it is hypothesized that glycinergic neurons mediate the inspiratory off-switch. Over the years, optogenetic tools have been developed that allow for cell-specific activation of subsets of neurons in vitro and in vivo. In this study, we aimed to identify the effect of activation of inhibitory neurons in vivo. Here, we used a conditional transgenic mouse line that expresses Channelrhodopsin 2 in inhibitory neurons. A 200 µm multimode optical fiber ferrule was implanted in adult mice using stereotaxic surgery, allowing us to stimulate inhibitory, respiratory neurons within the core excitatory network in the preBötzinger complex of the ventrolateral medulla. We show that, in anesthetized mice, activation of inhibitory neurons by blue light (470 nm) continuously or with stimulation frequencies above 10 Hz results in a significant reduction of the respiratory rate, in some cases leading to complete cessation of breathing. However, a lower stimulation frequency (4–5 Hz) could induce a significant increase in the respiratory rate. This phenomenon can be explained by the resetting of the respiratory cycle, since stimulation during inspiration shortened the associated breath and thereby increased the respiratory rate, while stimulation during the expiratory interval reduced the respiratory rate. Taken together, these results support the concept that activation of inhibitory neurons mediates phase-switching by inhibiting excitatory rhythmogenic neurons in the preBötzinger complex

Modulation of glycinergic neurotransmission may contribute to the analgesic effects of propacetamol

Treating neuropathic pain remains challenging, and therefore new pharmacological strategies are urgently required. Here, the enhancement of glycinergic neurotransmission by either facilitating glycine receptors (GlyR) or inhibiting glycine transporter (GlyT) function to increase extracellular glycine concentration appears promising. Propacetamol is a N,N-diethylester of acetaminophen, a non-opioid analgesic used to treat mild pain conditions. In vivo, it is hydrolysed into N,N-diethylglycine (DEG) and acetaminophen. DEG has structural similarities to known alternative GlyT1 substrates. In this study, we analyzed possible effects of propacetamol, or its metabolite N,N-diethylglycine (DEG), on GlyRs or GlyTs function by using a two-electrode voltage clamp approach in Xenopus laevis oocytes. Our data demonstrate that, although propacetamol or acetaminophen had no effect on the function of the analysed glycine-responsive proteins, the propacetamol metabolite DEG acted as a low-affine substrate for both GlyT1 (EC50 > 7.6 mM) and GlyT2 (EC50 > 5.2 mM). It also acted as a mild positive allosteric modulator of GlyRα1 function at intermediate concentrations. Taken together, our data show that DEG influences both glycine transporter and receptor function, and therefore could facilitate glycinergic neurotransmission in a multimodal manner