A pre-registered short-term forecasting study of COVID-19 in Germany and Poland during the second wave.

Disease modelling has had considerable policy impact during the ongoing COVID-19 pandemic, and it is increasingly acknowledged that combining multiple models can improve the reliability of outputs. Here we report insights from ten weeks of collaborative short-term forecasting of COVID-19 in Germany and Poland (12 October-19 December 2020). The study period covers the onset of the second wave in both countries, with tightening non-pharmaceutical interventions (NPIs) and subsequently a decay (Poland) or plateau and renewed increase (Germany) in reported cases. Thirteen independent teams provided probabilistic real-time forecasts of COVID-19 cases and deaths. These were reported for lead times of one to four weeks, with evaluation focused on one- and two-week horizons, which are less affected by changing NPIs. Heterogeneity between forecasts was considerable both in terms of point predictions and forecast spread. Ensemble forecasts showed good relative performance, in particular in terms of coverage, but did not clearly dominate single-model predictions. The study was preregistered and will be followed up in future phases of the pandemic.

The miR-106b-25 cluster mediates breast tumor initiation through activation of NOTCH1 via direct repression of NEDD4L.

Tumor-initiating cells (TIC) represent a subset of tumor cells with increased self-renewal capability. TICs display resistance to frontline cancer treatment and retain the ability to repopulate a tumor after therapy, leading to cancer relapse. NOTCH signaling has been identified as an important driver of the TIC population, yet mechanisms governing regulation of this pathway in cancer remain to be fully elucidated. Here we identify a novel mechanism of NOTCH regulation and TIC induction in breast cancer via the miR-106b-25 miRNA cluster. We show that the miR-106b-25 cluster upregulates NOTCH1 in multiple breast cancer cell lines, representing both estrogen receptor (ER+) and triple negative breast cancer (TNBC) through direct repression of the E3 ubiquitin ligase, NEDD4L. We further show that upregulation of NOTCH1 is necessary for TIC induction downstream of miR-106b-25 in both ER + and TNBC breast cancer cells, and that re-expression of NEDD4L is sufficient to reverse miR106b-25-mediated NOTCH1 upregulation and TIC induction. Importantly, we demonstrate a significant positive correlation between miR-106b-25 and NOTCH1 protein, yet a significant inverse correlation between miR-106b-25 and NEDD4L mRNA in human breast cancer, suggesting a critical role for the miR106b-25/NEDD4L/NOTCH1 axis in the disease. Further, we show for the first time that NEDD4L expression alone is significantly associated with a better relapse-free prognosis for breast cancer patients. These data expand our knowledge of the mechanisms underlying NOTCH activation and TIC induction in breast cancer, and may provide new avenues for the development of therapies targeting this resistant subset of tumor cells.

Asymmetry parameter of peaked Fano line shapes.

The spectroscopic line shape of electronic and vibrational excitations is ubiquitously described by a Fano profile. In the case of nearly symmetric and peaked Fano line shapes, the fit of the conventional Fano function to experimental data leads to difficulties in unambiguously extracting the asymmetry parameter, which may vary over orders of magnitude without degrading the quality of the fit. Moreover, the extracted asymmetry parameter depends on initially guessed values. Using the spectroscopic signature of the single-Co Kondo effect on Au(110) the ambiguity of the extracted asymmetry parameter is traced to the highly symmetric resonance profile combined with the inevitable scattering of experimental data. An improved parameterization of the conventional Fano function is suggested that enables the nonlinear optimization in a reduced parameter space. In addition, the presence of a global minimum in the sum of squared residuals and thus the independence of start parameters may conveniently be identified in a two-dimensional plot. An angular representation of the asymmetry parameter is suggested in order to reliably determine uncertainty margins via linear error propagation.

Recalibration methods to enhance information on prevalence rates from large mental health surveys.

Comparisons between self-report and clinical psychiatric measures have revealed considerable disagreement. It is unsafe to consider these measures as directly equivalent, so it would be valuable to have a reliable recalibration of one measure in terms of the other. We evaluated multiple imputation incorporating a Bayesian approach, and a fully Bayesian method, to recalibrate diagnoses from a self-report survey interview in terms of those from a clinical interview with data from a two-phase national household survey for a practical application, and artificial data for simulation studies. The most important factors in obtaining a precise and accurate 'clinical' prevalence estimate from self-report data were (a) good agreement between the two diagnostic measures and (b) a sufficiently large set of calibration data with diagnoses based on both kinds of interview from the same group of subjects. From the case study, calibration data on 612 subjects were sufficient to yield estimates of the total prevalence of anxiety, depression or neurosis with a precision in the region of +/-2%. The limitations of the calibration method demonstrate the need to increase agreement between survey and reference measures by improving lay interviews and their diagnostic algorithms.

Minimal invasive treatment of proximal femur fractures with the long gamma nail: indication, technique, results.

BACKGROUND: The surgical treatment of complex unstable proximal femur fractures from the trochanteric region to the middle shaft area is difficult and often highly invasive, especially in older patients with osteoporotic bones. METHODS: In 1993, we began to treat all unstable proximal femur fractures from the trochanteric region to the middle third of the shaft with the long gamma nail (LGN) and allowed the patients immediate full weightbearing after surgery. Perioperative, postoperative, and follow-up data were analyzed. RESULTS: During a 3-year period, we treated 37 patients with unstable proximal femur fractures with the LGN. Five of the patients had sustained pathological fractures, and four patients had sustained multiple trauma. The 37 operations were performed by 22 different surgeons with varying degrees of experience. The LGN implantations through maximal 40-mm skin incisions were performed in a mean skin-to-skin operation time of 125 minutes (range, 65-200 minutes) without any further complications. Thirty-one of the 37 patients were allowed immediate full weightbearing after the second postoperative day. The six patients who were not allowed full weightbearing were the ones who had multiple trauma (4) and those who were unable to walk before surgery (2). Three postoperative complications were as follows: one deep infection 4 months after surgery, one superficial infection 3 weeks after surgery, and one deep vein thrombosis 2 weeks after discharge. All three complications occurred in the group of patients who had sustained only one trauma. All traumatic fractures (n = 32) healed without any bone grafting, which means a union rate of 100%. Although immediate full weightbearing was allowed, there were no implant dislocations, implant failures, or other problems. The 30-day mortality was 0%. The follow-up examinations after a mean time of 6 months were very satisfying. All traumatic fractures were healed. The patients had symmetrical functional findings to the opposite side or before surgery, respectively, except for two patients with a leg shortening of 2 cm, two patients with an external malrotation of 10 degrees, and one patient with a hip extension deficit of 10 degrees after a pathological fracture. CONCLUSION: The LGN is, after appropriate introduction and training, a safe and easy implant for the treatment of complex proximal femur fractures from the trochanteric region to the middle shaft area. The minimal invasive technique with low risks and minimal complications and the possibility of immediate full weightbearing sets a new standard, especially for older patients with osteoporotic bones.

[Distal biceps tendon ruptures--experiences with soft tissue preserving reinsertion by bone anchors]. / Distale Bizepssehnenrupturen--Erfahrungen mit der weichteilschonenden Reinsertion mittels Knochenankern.

The repair of the distal biceps tendon rupture with bone anchors achieves excellent results. The important function of the M. biceps brachii as a powerful supinator and flexor can be reestablished and the soft tissue can be protected. We describe the repair of the rupture of distal biceps tendon by an anatomic refixation of the tendon to the tuberositas radii with bone anchors through a single anterior incision. In a four year period we treated eight patients with this technique. All patients were men with a mean age of 50 years. In each case the mechanism of injury was a single traumatic event with a large load on the flexed elbow. In average surgery was performed within five days and the patients stayed in the hospital for two days. Clinical follow up after almost two years showed no nerve damage or heterotopic bone formation. The range of motion and isometric muscle testing were almost symmetrical. All patients were able to return to preinjury activity level without any limitations.

[Inguinal hernia 1998--an assessment of current status]. / Leistenhernienchirurgie 1998--eine Standortbestimmung.

Hernia surgery has considerably changed in recent years. In the era of minimal invasive surgery classical Shouldice repair has become old-fashioned and is increasingly replaced by tension-free techniques using synthetic mesh material. Currently, Shouldice repair remains the treatment of choice in young patients with small primary hernia. Lichtenstein hernioplasty is indicated in young patients with large hernias, and in those over 35 years of age for any size of hernias. Endoscopic operations are restricted to bilateral primary hernias and recurrent hernias. In future, when used on the basis of a reasonable strategy, the variety of operative procedures offers a chance to improve the results of hernia surgery. Further studies are needed to demonstrate which hernia strategy is most reliable in terms of cost-effectiveness, patient comfort, complication and recurrence rate.

[Inline skating, an old sport, newly discovered: harmless or a potential danger with socioeconomic effects?]. / In-line Skating, eine alte Sportart, neu entdeckt: Harmlos oder ein Gefahrenpotential mit sozioökonomischen Auswirkungen?

Over a period of one year, all accidents associated with in-line skating (ILS) were surveyed. Sport-specific data was recorded with a standardized questionnaire. The study comprised 66 patients with 75 injuries (48 upper limb, 16 skull, eight lower limb, three trunk). We were looking after 42 male and 24 female patients with an average age of 20 years (5-53 years). Twenty-seven patients (40%) had to be treated as inpatients. Overall, the most frequent injury (one third of all injuries) was forearm fracture close to the wrist (21 radius fractures, four radioulnar fractures). It had to be reset in 20 cases. Additional internal fixation was required in 10 cases (Kirschner wire osteosynthesis, intramedullary nailing or plate osteosynthesis). Only five patients could be treated with plaster cast fixation alone. Most patients with injuries in the vicinity of the wrist were not wearing a wrist protector at the time of the accident. The most frequent reasons given for not wearing protectors was forgetfulness or the high price of protectors. However, there were also two distal radius fractures and a disc injury in the wrist in patients who had been wearing wrist protectors. In most cases, ILS accidents lead to appreciable damage requiring a healing period of several weeks to months (average period of loss of work 41 days). The bfu (advisory center for accident prevention) reckons with 60,000 ILS cases annually in Switzerland. These injuries are thus of great socioeconomic importance. In the future, better risk behavior must be achieved by informing the population (wearing protectors, especially for the wrist and head, attendance of training courses).

Cardiocirculatory, hormonal, and metabolic reactions to various forms of ergometric tests.

The sympathoadrenergic reaction is not only dependent on the duration and intensity of work but also on the body position and the involvement of small or large muscle masses. This observation made in field tests comparing different sports disciplines such as swimming, running, or diving encouraged us to investigate this topic under the following laboratory conditions. Twelve healthy sport students participated in ergometric tests on a bicycle ergometer in a horizontal and vertical body position as well as on a treadmill and a swim bench ergometer. The changes of plasma catecholamines (CA) obtained in the different ergometric tests were compared with those cardiocirculatory, metabolic, and hormonal parameters which can be influenced by the sympathoadrenergic stimulation. In the horizontal body position we found a smaller increase of norepinephrine at submaximal and maximal work loads combined with a similar reaction of renin, whereas the diastolic blood pressure and the mean arterial blood pressure increased more. The substrates of lipolysis and aerobic and anaerobic glycolysis did not show obvious differences depending on the body position. In the swim bench test, however, the lactate increase started earlier and was comparatively higher than in the other ergometric tests in which the maximal work load and VO2max were higher. Although a smaller muscle mass was used and a lower maximal oxygen uptake was reached, we did not find statistically different CA values during the swim bench ergometric test compared with the bicycle ergometric test in a horizontal body position. In our ergometric tests, the venous CA levels (especially norepinephrine) were predominantly influenced by the body position.