Reconstruction and simulation of neocortical microcircuitry

We present a first-draft digital reconstruction of the microcircuitry of somatosensory cortex of juvenile rat. The reconstruction uses cellular and synaptic organizing principles to algorithmically reconstruct detailed anatomy and physiology from sparse experimental data. An objective anatomical method defines a neocortical volume of 0.29 ± 0.01 mm3 containing ∼31,000 neurons, and patch-clamp studies identify 55 layer-specific morphological and 207 morpho-electrical neuron subtypes. When digitally reconstructed neurons are positioned in the volume and synapse formation is restricted to biological bouton densities and numbers of synapses per connection, their overlapping arbors form ∼8 million connections with ∼37 million synapses. Simulations reproduce an array of in vitro and in vivo experiments without parameter tuning. Additionally, we find a spectrum of network states with a sharp transition from synchronous to asynchronous activity, modulated by physiological mechanisms. The spectrum of network states, dynamically reconfigured around this transition, supports diverse information processing strategies

Deutsches Staatsrecht | Erster Band: Die Grundlagen des deutschen Staates und die Reichsgewalt. Systematisches Handbuch der Deutschen Rechtswissenschaft. Fünfte Abtheilung, erster Theil. Hrsg. von Karl Binding

Das vorliegende Werk erschien als fünfter Teil des von Karl Binding herausgegebenen Werkes »Systematisches Handbuch der Deutschen Rechtswissenschaft« und ist auf zwei Bände ausgelegt. Darin behandelt der Rechtswissenschaftler Albert Hänel das Deutsche Staatsrecht. Der erste Band gliedert sich in zwei Teile: Im ersten Teil behandelt Hänel die Grundlagen des Deutschen Staates. Die abgehandelten Themen reichen dabei von dem Bestand der deutschen Verfassung bis zu den staatsrechtlichen Grundverhältnissen. Der wesentlich umfangreichere zweite Teil ist mit »Die Reichsgewalt« überschrieben. Behandelt werden darin unter anderem die Regierungsgewalt, die Verwaltung sowie die Kompetenz-Kompetenz

Ergonomic Comparison of Four Dental Workplace Concepts Using Inertial Motion Capture for Dentists and Dental Assistants

When the inventory is arranged in a dental practice, a distinction can be made between four different dental workplace concepts (DWCs). Since the prevalence of musculoskeletal diseases in dental professionals is very high, preventive solution need to be investigated. As the conventionally used DWCs have, to date, never been studied in terms of their ergonomics, this study aims to investigate the ergonomic risk when working at the four different DWCs. In total, 75 dentists (37 m/38 f) and 75 dental assistants (16 m/59 f) volunteered to take part in this study. Standardized cooperative working procedures were carried out in a laboratory setting and kinematic data were recorded using an inertial motion capture system. The data were applied to an automated version of the Rapid Upper Limb Assessment (RULA). Comparisons between the DWCs and between the dentists and dental assistants were calculated. In all four DWCs, both dentists and dental assistants spent 95–97% of their working time in the worst possible RULA score. In the trunk, DWCs 1 and 2 were slightly favorable for both dentists and dental assistants, while for the neck, DWC 4 showed a lower risk score for dentists. The ergonomic risk was extremely high in all four DWCs, while only slight advantages for distinct body parts were found. The working posture seemed to be determined by the task itself rather than by the different inventory arrangements

Prevalence of Musculoskeletal Disorders among Dentists and Dental Students in Germany

Background: Dentists are at a higher risk of suffering from musculoskeletal disorders (MSD) than the general population. However, the latest study investigating MSD in the dental profession in Germany was published about 20 years ago. Therefore, the aim of this study was to reveal the current prevalence of MSD in dentists and dental students in Germany. Methods: The final study size contained 450 (287 f/163 m) subjects of different areas of specialization. The age of the participants ranged from 23 to 75 years. The questionnaire consisted of a modified version of the Nordic Questionnaire, work-related questions from the latest questionnaire of German dentists, typical medical conditions and self-developed questions. Results: The overall prevalence showed that dentists suffered frequently from MSD (seven days: 65.6%, twelve months: 92%, lifetime: 95.8%). The most affected body regions included the neck (42.7%–70.9%–78.4%), shoulders (29.8%–55.6%–66.2%) and lower back (22.9%–45.8%–58.7%). Overall, female participants stated that they suffered from pain significantly more frequently, especially in the neck, shoulders and upper back. Conclusion: The prevalence of MSD among dentists, especially in the neck, shoulder and back area, was significantly higher than in the general population. In addition, women suffered more frequently from MSD than men in almost all body regions

Prevalence of self-reported musculoskeletal disorders of the hand and associated conducted therapy approaches among dentists and dental assistants in Germany.

BackgroundDental professionals are subjected to higher risks for musculoskeletal disorders (MSDs) than other professional groups, especially the hand region. This study aims to investigate the prevalence of hand complaints among dentists (Ds) and dental assistants (DAs) and examines applied therapies.MethodsFor this purpose, an online questionnaire analysed 389 Ds (240female/149male) and 406 DAs (401female/5male) working in Germany. The self-reported data of the two occupational groups were compared with regard to the topics examined. The questionnaire was based on the Nordic Questionnaire (self-reported lifetime, 12-month and 7-day MSDs prevalence of the hand, the conducted therapy and its success), additional occupational and sociodemographic questions as well as questions about specific medical conditions.Results30.8% of Ds affirmed MSDs in the hand at any time in their lives, 20.3% in the last twelve months and 9.5% in the last seven days. Among DAs, 42.6% reported a prevalence of MSDs in the hand at any time in their lives, 31.8% in the last 12 months and 15.3% in the last seven days. 37.5% of the Ds and 28.3% of the DAs stated that they had certain treatments. For both, Ds and DAs, physiotherapy was the most frequently chosen form of therapy. 89.7% of Ds and 63.3% of DAs who received therapy reported an improvement of MSDs.ConclusionAlthough the prevalence of MSDs on the hand is higher among DAs than among Ds, the use of therapeutic options and the success of therapy is lower for DAs compared to Ds

Daratumumab, carfilzomib, and dexamethasone in relapsed or refractory myeloma: final analysis of PLEIADES and EQUULEUS

Daratumumab is approved in many countries as monotherapy and in combination regimens for relapsed/refractory multiple myeloma (RRMM) and newly diagnosed multiple myeloma [1–3]. Daratumumab-based combinations have also demonstrated encouraging efficacy in lenalidomide-refractory RRMM [4, 5]. Carfilzomib is approved as monotherapy and in combination regimens, including daratumumab and dexamethasone (D-Kd), for RRMM [6]. In the phase 3 CANDOR study, D-Kd (intravenous [IV] daratumumab; carfilzomib 56 mg/m2 twice weekly) improved progression-free survival (PFS) versus Kd in the overall population and lenalidomide-refractory patients [7, 8]. In the phase 3 A.R.R.O.W. study, once-weekly carfilzomib (70 mg/m 2 ) significantly prolonged PFS versus twice-weekly carfilzomib (27 mg/m 2 ), providing a safe and more convenient Kd dosing regimen [9]. Preliminary results from the phase 2 PLEIADES study (median follow-up, 9.2 months) and the phase 1b EQUULEUS study (median follow-up, 16.6 months) showed that combining subcutaneous daratumumab (DARA SC) and daratumumab IV, respectively, with Kd (carfilzomib 70 mg/m2 weekly) was well tolerated and induced deep responses in RRMM patients [10, 11]. We report final data from PLEIADES and EQUULEUS, with a median follow-up of 12.4 and 23.7 months, respectively.Medicin