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We study scheduling problems with release times and rejection costs with the objective function of minimizing the maximum lateness. Our main result is a PTAS for the single machine problem with an upper bound on the rejection costs. This result is extended to parallel, identical machines. The corresponding problem of minimizing the rejection costs with an upper bound on the lateness is also examined. We show how to compute a PTAS for determining an approximation of the Pareto frontier on both objective functions on parallel, identical machines. Moreover, we present an FPTAS with strongly polynomial time for the maximum lateness problem without release times on identical machines when the number of machines is constant. Finally, we extend this FPTAS to the case of unrelated machines.

ObjectiveNoisy galvanic vestibular stimulation (nGVS) has been shown to partly restore vestibular function and to stabilize stance and gait in patients with incomplete bilateral vestibulopathy (BVP). Here, we examined potential synergistic effects of nGVS when combined with standardized vestibular rehabilitation training (VRT).Methods23 patients with confirmed BVP received a 30-min vestibular rehabilitation training (VRT) program three times a week for 2 weeks. The intervention group (n = 12) was stimulated with nGVS (at individually determined optimal amplitudes) during training, whereas the control group (n = 11) received zero-amplitude nGVS (sham stimulation) during training. Outcome measurements assessed at baseline, after 2 weeks of training, and at 2-week follow-up included quantitative posturography, instrumented gait analysis, Timed Up and Go Test (TUG), Functional Gait Assessment (FGA), and clinical scores related to quality of life and balance confidence.ResultsAfter 2 weeks of VRT, all patients showed moderate improvement in balance. Irrespective of nGVS treatment, performance improved in the TUG (p < 0.013), and in the FGA (p < 0.040). Furthermore, base of support when walking with closed eyes was reduced after 2-week training (p < 0.003). Postural sway did not change. There was no difference between groups and thereby no evidence for an additional influence of nGVS on the VRT treatment effects.ConclusionnGVS does not induce synergistic treatment effects in combination with VRT in patients with BVP when applied during treatment sessions. Hence, rather than being applied in parallel, nGVS and VRT might be complementary therapeutic options with nGVS being used during postural activities in daily life, e.g., walking.

Deep tissue imaging with high contrast close to or even below the optical resolution limit is still challenging due to optical aberrations and scattering introduced by dense biological samples. This results in high complexity and cost of microscopes that can facilitate such challenges. Here, we demonstrate a cost-effective and simple to implement method to turn most two-photon laser-scanning microscopes into a super-resolution microscope for deep tissue imaging. We realize this by adding inexpensive optical devices, namely a cylindrical lens, a field rotator, and a sCMOS camera to these systems. By combining two-photon excitation with patterned line-scanning and subsequent image reconstruction, we achieve imaging of sub-cellular structures in Pinus radiata , mouse heart muscle and zebrafish. In addition, the penetration depth of super-resolved imaging in highly scattering tissue is considerably extended by using the camera’s lightsheet shutter mode. The flexibility of our method allows the examination of a variety of thick samples with a variety of fluorescent markers and microscope objective lenses. Thus, with a cost-efficient modification of a multi-photon microscope, an up to twofold resolution enhancement is demonstrated down to at least 70 μ m deep in tissue. This article presents structured illumination microscopy in deep tissue. With minor modifications to a two-photon microscope, the authors overcome scattering in dense biological samples, achieving 150 nm lateral resolution in depths down to 70 μm.

Recent findings suggest an association between obesity, loss of gut barrier function and changes in microbiota profiles. Our primary objective was to examine the effect of caloric restriction and subsequent weight reduction on gut permeability in obese women. The impact on inflammatory markers and fecal microbiota was also investigated. The 4-week very-low calorie diet (VLCD, 800 kcal/day) induced a mean weight loss of 6.9 ± 1.9 kg accompanied by a reduction in HOMA-IR (Homeostasis model assessment-insulin resistance), fasting plasma glucose and insulin, plasma leptin, and leptin gene expression in subcutaneous adipose tissue. Plasma high-molecular weight adiponectin (HMW adiponectin) was significantly increased after VLCD. Plasma levels of high-sensitivity C-reactive protein (hsCRP) and lipopolysaccharide-binding protein (LBP) were significantly decreased after 28 days of VLCD. Using three different methods, gut paracellular permeability was decreased after VLCD. These changes in clinical parameters were not associated with major consistent changes in dominant bacterial communities in feces. In summary, a 4-week caloric restriction resulted in significant weight loss, improved gut barrier integrity and reduced systemic inflammation in obese women.

Background Previous studies indicate that imbalance in patients with bilateral vestibulopathy (BVP) may be reduced by treatment with low-intensity noisy galvanic vestibular stimulation (nGVS). Objective To elucidate the potential mechanisms underlying this therapeutic effect. In particular, we determined whether nGVS-induced balance improvements in patients are compatible with stochastic resonance (SR)—a mechanism by which weak noise stimulation can paradoxically enhance sensory signal processing. Methods Effects of nGVS of varying intensities (0–0.7 mA) on body sway were examined in 19 patients with BVP standing with eye closed on a posturographic force plate. We assumed a bell-shaped response curve with maximal sway reductions at intermediate nGVS intensities to be indicative of SR. An established SR curve model was fitted on individual patient outcomes, and three experienced human raters had to judge whether responses to nGVS were consistent with the exhibition of SR. Results nGVS-induced reductions of body sway compatible with SR were found in 12 patients (63%) with optimal improvements of 31 ± 21%. In 10 patients (53%), nGVS-induced sway reductions exceeded the minimally important clinical difference (optimal improvement: 35 ± 21%), indicative of strong SR. This beneficial effect was more likely in patients with severe vestibular loss (i.e. lower video head impulse test gain; R  = 0.663; p  = 0.002) and considerable postural imbalance (baseline body sway; R  = 0.616; p  = 0.005). Conclusions More than half of the assessed patients showed robust improvements in postural balance compatible with SR when treated with nGVS. In particular, patients with a higher burden of disease may benefit from the non-invasive and well-tolerated treatment with nGVS.

National and international medical societies have published guidelines and recommendations pertaining to the diagnostics and monitoring of chronic kidney disease in patients with type 2 diabetes mellitus. Consistency and implementation in daily clinical practice are rarely reported.BACKGROUNDNational and international medical societies have published guidelines and recommendations pertaining to the diagnostics and monitoring of chronic kidney disease in patients with type 2 diabetes mellitus. Consistency and implementation in daily clinical practice are rarely reported.This article provides an overview on recommendations as a reflection of the global state of the art and assesses the implementation in daily practice in Germany, which was collected via a representative questionnaire.OBJECTIVEThis article provides an overview on recommendations as a reflection of the global state of the art and assesses the implementation in daily practice in Germany, which was collected via a representative questionnaire.The current guidelines were compared with respect to the consistency of parameters, frequency of testing and recommendations for nephrological referrals. The results were then compared with the survey responses to estimate the level of their implementation in daily practice in Germany.MATERIAL AND METHODSThe current guidelines were compared with respect to the consistency of parameters, frequency of testing and recommendations for nephrological referrals. The results were then compared with the survey responses to estimate the level of their implementation in daily practice in Germany.According to the recommendations the estimated glomerular filtration rate (eGFR) and the urine albumin to creatinine ratio (UACR) should be tested at least once per year in all patients with type 2 diabetes. In cases of more severe kidney impairment (above Kidney Disease:Improving Global Outcomes, KDIGO, stage 3b with eGFR < 45 ml/min/1,73 m2) or albuminuria (from stage A2), more frequent measurements and nephrological referrals are recommended; however, different threshold values and frequencies are recommended. The responses from the questionnaires indicate that eGFR is tested annually in 96.5% of all cases and albuminuria is tested in 77.2% of cases. An eGRF triggered referral to a nephrologist is implemented by 19.6% of all nonnephrological practitioners, albuminuria triggered referrals are implemented in the majority of cases.RESULTSAccording to the recommendations the estimated glomerular filtration rate (eGFR) and the urine albumin to creatinine ratio (UACR) should be tested at least once per year in all patients with type 2 diabetes. In cases of more severe kidney impairment (above Kidney Disease:Improving Global Outcomes, KDIGO, stage 3b with eGFR < 45 ml/min/1,73 m2) or albuminuria (from stage A2), more frequent measurements and nephrological referrals are recommended; however, different threshold values and frequencies are recommended. The responses from the questionnaires indicate that eGFR is tested annually in 96.5% of all cases and albuminuria is tested in 77.2% of cases. An eGRF triggered referral to a nephrologist is implemented by 19.6% of all nonnephrological practitioners, albuminuria triggered referrals are implemented in the majority of cases.Measurement of eGFR is the established standard in Germany. Potential improvement was found in albumin measurement, the frequency of testing and the time point for nephrological consultation. All guidelines emphasize the benefits of interdisciplinary cooperation.CONCLUSIONMeasurement of eGFR is the established standard in Germany. Potential improvement was found in albumin measurement, the frequency of testing and the time point for nephrological consultation. All guidelines emphasize the benefits of interdisciplinary cooperation.

Background Recent epidemic outbreaks such as the SARS-CoV-2 pandemic and the mpox outbreak in 2022 have demonstrated the value of genomic sequencing data for tracking the origin and spread of pathogens. Laboratories around the globe generated new sequences at unprecedented speed and volume and bioinformaticians developed new tools and dashboards to analyze this wealth of data. However, a major challenge that remains is the lack of simple and efficient approaches for accessing and processing sequencing data. Results The Lightweight API for Sequences (LAPIS) facilitates rapid retrieval and analysis of genomic sequencing data through a REST API. It supports complex mutation- and metadata-based queries and can perform aggregation operations on massive datasets. LAPIS is optimized for typical questions relevant to genomic epidemiology. Using a newly-developed in-memory database engine, it has a high speed and throughput: between 25 January and 4 February 2023, the SARS-CoV-2 instance of LAPIS, which contains 14.5 million sequences, processed over 20 million requests with a mean response time of 411 ms and a median response time of 1 ms. LAPIS is the core engine behind our dashboards on genspectrum.org and we currently maintain public LAPIS instances for SARS-CoV-2 and mpox. Conclusions Powered by an optimized database engine and available through a web API, LAPIS enhances the accessibility of genomic sequencing data. It is designed to serve as a common backend for dashboards and analyses with the potential to be integrated into common database platforms such as GenBank.

Recent clinical practice guidelines for diabetes, obesity, cardiovascular disease (CVD) and chronic kidney disease (CKD) emphasise a holistic, person-centred approach to care. However, they do not include recommendations for the assessment of patient-reported outcomes (PROs), which would – dependent on the topic of guideline – be important for improving shared decision-making, patients’ concordance with guideline recommendations, clinical outcomes and health-related quality of life (HRQoL). The Taskforce of the Guideline Workshop discussed PROs in diabetes, obesity, CVD and CKD as well as the relevance of their inclusion in clinical practice guidelines for the management of these conditions. Highlights Patient engagement in disease management is a topic that is becoming increasingly important, also in terms of improving clinical outcomes Person-reported outcome measures (PROMs) are tools to assess person-reported outcomes (PROs) in an efficient and standardized manner Validated disease-specific measures for diabetes, obesity, CVD, and CKD as well as generic measures are available Currently underutilised in the routine care of cardio-renal-metabolic diseases, the integration of recommendations on PROs and PROMs into clinical practice guidelines may help to overcome the barriers to their implementation

We discuss a layer-oriented approach to multi-conjugate adaptive optics (MCAO) in solar imaging. The technique is a complement to the current star-oriented MCAO and appears as a necessary alternative when large field sizes are desired in solar observations. The basic procedure of the layer oriented method is indicated, and its characteristics are then illustrated in terms of numerical simulations.