3D printing of resilient biogels for omnidirectional and exteroceptive soft actuators.

Soft robotics greatly benefits from nature as a source of inspiration, introducing innate means of safe interaction between robotic appliances and living organisms. In contrast, the materials involved are often nonbiodegradable or stem from nonrenewable resources, contributing to an ever-growing environmental footprint. Furthermore, conventional manufacturing methods, such as mold casting, are not suitable for replicating or imitating the complexity of nature's creations. Consequently, the inclusion of sustainability concepts alongside the development of new fabrication procedures is required. We report a customized 3D-printing process based on fused deposition modeling, printing a fully biodegradable gelatin-based hydrogel (biogel) ink into dimensionally stable, complex objects. This process enables fast and cost-effective prototyping of resilient, soft robotic applications from gels that stretch to six times their original length, as well as an accessible recycling procedure with zero waste. We present printed pneumatic actuators performing omnidirectional movement at fast response times (less than a second), featuring integrated 3D-printed stretchable waveguides, capable of both proprio- and exteroception. These soft devices are endowed with dynamic real-time control capable of automated search-and-wipe routines to detect and remove obstacles. They can be reprinted several times or disposed of hazard-free at the end of their lifetime, potentially unlocking a sustainable future for soft robotics.

Foehn-cold pool interactions in the Inn Valley during PIANO IOP2.

A case-study is presented of a south foehn emanating from the Wipp Valley, Austria, which encountered a cold-air pool (CAP) in the Inn Valley near the city of Innsbruck. The analysis is based on data collected during the second Intensive Observation Period of the Penetration and Interruption of Alpine Foehn (PIANO) field experiment. Foehn was initiated on 3 November 2017 by an eastward moving trough and terminated in the afternoon of 5 November 2017 by a cold front passage. On two occasions, reversed foehn flow deflected at the mountain ridge north of Innsbruck penetrated to the bottom of the Inn Valley. The first breakthrough occurred in the afternoon of 4 November 2017. It was transient and locally limited to the northwest of the city. The second (final) breakthrough occurred in the morning of 5 November 2017 and was recorded by all surface stations in the vicinity of Innsbruck. It started with a foehn air intrusion to the northeast of Innsbruck and continued with the westward propagation of the foehn-CAP boundary along the valley. Subsequently observed northerly winds above the city were caused by an atmospheric rotor. A few hours later and prior to the cold front passage, the CAP pushed back and lifted the foehn air from the ground. During both nights, shear flow instabilities formed at the foehn-CAP interface, which resulted in turbulent heating of the CAP and cooling of the foehn. However, this turbulent heating/cooling was partly compensated by other mechanisms. Especially in the presence of strong spatial CAP heterogeneity during the second night, heating in the CAP was most likely overcompensated by negative horizontal temperature advection.

Impact of Pre-existing Comorbidities on Long-term Outcomes in Kidney Transplant Recipients.

BACKGROUND: Outcomes of patients with end-stage renal disease are mainly affected by their comorbidities. Detailed data evaluating the impact of pre-transplant comorbidities on long-term outcome after kidney transplantation are largely missing. METHODS: In a long-term retrospective analysis, we investigated 839 deceased donor kidney transplant recipients (KTRs) who received transplants between 1999 and 2014. The prevalence and impact of the most relevant comorbidities were studied in detail. RESULTS: At the time of transplantation, 25% of KTRs had coronary artery disease (CAD), 16% had diabetes mellitus (DM), 11% had peripheral arterial disease (PAD), 8% had chronic heart failure (CHF), and 7% had cerebrovascular disease (CVD). KTRs with pre-existing CAD, DM, PAD, and CHF showed a significantly inferior patient survival. Multivariate analysis adjusting for all relevant factors and comorbidities confirmed CAD as most hazardous independent risk factor for premature death (hazard ratio [HR] 1.70; P = .002). A multivariate analysis revealed CHF and PAD as independent risk factors for death censored graft loss (HR 2.20; P = .003 and HR 1.80; P = .013). Diabetes was independently and significantly associated with T-cell- (HR 1.46; P = .020) and antibody-mediated rejections (HR 2.27; P = .030). CONCLUSIONS: Detailed quantification of the impact of pre-transplant comorbidities may facilitate the evaluation of transplant candidates, guide post-transplant follow-up, and may help to further refine prediction algorithms and allocation systems.

Immunologic Long-term Outcomes of Living-Related Kidney Transplantations Depending on the Donor-Recipient Relationship.

BACKGROUND: The aim of this study is to analyze the long-term immunologic outcomes of living-related kidney transplantations depending on the donor-recipient relationship. METHODS: This retrospective single-center study included adult kidney transplant recipients (KTR) transplanted between 2000 and 2014. Among 1117 KTRs, 178 patients (15.9%) received living-related donations. Those patients were further categorized according to the donor-recipient relationship: 65 transplantations between siblings, 39 father-to-child (F-t-C) and 74 mother-to-child (M-t-C) donations. Allograft biopsies were performed for clinically suspected rejections. Data analysis included patient and graft survival, biopsy proven rejections (T-cell mediated [TCMR] or antibody mediated) and development of de novo donor-specific antibody. Outcome data were assessed over a period of a maximum 14 years. RESULTS: There was no significant difference between the groups (F-t-C, M-t-C, and siblings) with regard to HLA-mismatches, prior kidney transplantations, time on dialysis, and cold ischemia time. Among KTRs with related donors, the type of relationship had no significant influence on graft survival. F-t-C and M-t-C pairs showed comparable incidences of TCMR at 7 years post-transplantation, both significantly exceeding the rate in sibling-to-sibling pairs (26.2% and 26.8% vs 10%, respectively; P = .043). A multivariate Cox regression analysis adjusted for recipient age, donor age, and HLA (A, B, DR)-mismatches identified both M-t-C- and F-t-C-donations as important independent risk factors for TCMR (hazard ratio: 8.13; P < .001 and hazard ratio: 8.09; P = .001, respectively). There was no significant difference between the groups concerning the incidence of antibody-mediated rejection and de novo donor-specific antibody. CONCLUSION: Our results indicate that parent-to-child kidney donation is an independent risk factor for TCMR.

Incidence of Infectious Disease and Malignancies After Rituximab Therapy in Kidney Transplant Recipients: Results From a Cohort in Germany.

BACKGROUND: Rituximab is frequently used in solid organ transplantation off-label, especially in patients with renal allografts. Few data are available on the safety aspects of solid organ transplant recipients receiving rituximab. There is a knowledge gap on long-term follow-up data, in particular on infectious complications. PATIENTS AND METHODS: A retrospective observational registry study (German Registry on Autoimmune Diseases) comprising a total of 681 patients was conducted. The data of 63 adult kidney transplant recipients who received rituximab between 2006 and 2013 were used in this analysis. RESULTS: Median follow-up was 42 (1-109) months. At least 1 severe infection occurred in 57% of patients. The median time between the first rituximab infusion and the first infection was 4 (1-48) months. Of the overall 88 infections, 74 were severe bacterial infections, 5 were severe viral infections, 3 were severe fungal infections, 2 were combined severe bacterial and fungal infections, and 4 were combined severe viral, fungal and bacterial infections. Seven patients died during the observational period, 2 of them due to infectious complications. In the observational period, 1 case of squamous cell carcinoma but no other malignancies were observed. CONCLUSION: Consistent with previous data, a high incidence of infections was observed after rituximab treatment in kidney transplant recipients. Most infections occurred within 6 months after rituximab initiation. With more than 3 years of follow-up, we were able to document a low incidence of secondary malignancies after rituximab with only 1 case in our cohort.

Prolonged Low-Dose Prophylaxis With Valganciclovir in Cytomegalovirus-Negative Recipients of Kidney Transplants From Cytomegalovirus-Positive Donors Allows Seroconversion and Prevents Cytomegalovirus Disease.

BACKGROUND: Cytomegalovirus-negative recipients of kidneys from cytomegalovirus (CMV)-positive donors (D+/R-) are at high risk to develop severe clinical manifestations of CMV disease. Long-term data about incidence and timing of CMV seroconversion, CMV disease, and the influence of prolonged valganciclovir prophylaxis on the clinical course of CMV infection are missing. METHODS: We conducted a retrospective long-term study of 89 consecutive CMV D+/R- kidney transplant recipients transplanted between 2003 and 2012. All recipients received valganciclovir prophylaxis after transplantation (median 187 [126-261] days) with a median dose of 213 (181-338) mg/d. Long-term outcome was assessed over a maximum of 10 years post-transplant. RESULTS: During follow-up (median 62 months) 60 of 89 (67%) patients had CMV seroconversion, and 29 of 89 (33%) developed symptomatic CMV disease. In addition, in 38 of the 60 (63%), seroconversion occurred during prophylaxis (median 154 days post-transplant), and in 22 patients, after the end of prophylaxis (median 320 days after transplantation). Baseline characteristics of the 2 groups did not differ significantly. Seroconversion during prophylaxis vs seroconversion after the end of prophylaxis was associated with significantly lower incidence of CMV disease (34% vs 73%, P = .007), less severe CMV disease (16% vs 64%, P < .001), and fewer organ manifestations (26% vs 64%, P = .006). The risk of CMV disease was limited to the first 475 days after transplantation. Valganciclovir resistance occurred in just 1 case (1%). CONCLUSIONS: Prolonged prophylaxis with low-dose valganciclovir allowed CMV seroconversion during prophylaxis in a high proportion of D+/R- patients. Seroconversion occurred after a median of 154 days and was associated with significantly lower incidence of CMV disease, less severe CMV disease, and fewer CMV complications.

Need for optimized immunosuppression in elderly kidney transplant recipients.

The proportion of elderly kidney transplant candidates is increasing worldwide due to higher number of patients with end-stage renal disease in aging societies. ALLOCATION: Accordingly, organ allocation policies in this population were adjusted in several countries. The European Senior Program is the most prominent example, where elderly patients (≥65years) receive elderly (≥65years) donor organs with acceptable results. IMMUNOSENESCENCE: Because of age-dependent changes in the immune response and higher susceptibility to immunosuppressant side effects, outcomes in elderly patients are different compared to younger kidney transplant recipients. However, elderly patients do reject, especially poorly matched elderly donor organs. This warrants tailored immunosuppressive regimes with regard to the age-related changes of the immune system. SIDE EFFECTS: Rejection therapies may have detrimental side effects in the seniors and are frequently leading to over-immunosuppression (malignancy and infections) in long-term therapy. It is hypothesized that after initial graft adaptation elderly patients may benefit from less immunosuppression in order to lower cancer risk and reduce infection rates and cardiovascular comorbidities. LACK OF DATA: Current evidence on recommended standard immunosuppressive therapy was mainly derived from trials, where elderly patients were excluded or only a minority. In order to improve immunosuppressive therapy in elderly transplant recipients, current immunosuppressive regimes have to be re-investigated in this growing population. Up to date, only a few well-designed prospective studies were performed in elderly populations and demonstrate the need for effective immunosuppression in the first months after transplantation. CONCLUSION: It is evident that novel treatment strategies and adequately powered prospective clinical trials are needed to establish time-adapted immunosuppressive regimens according to the needs of this vulnerable group of kidney transplant recipients.

Grazing collisions of black holes via the excision of singularities.

We present the first simulations of non-head-on (grazing) collisions of binary black holes in which the singularities are excised from the simulation. Initially equal mass m black holes (spinning or not) are separated by approximately 10m and with impact parameter approximately 2m. Evolutions to t approximately 35m are obtained where two separate horizons are present for t approximately 3.8m; then a single enveloping horizon forms indicating that the holes merged. Apparent horizon area estimates suggest gravitational radiation of about 2%-3% of the total mass. The evolutions end after a moderate amount of time because of instabilities.

Physiological responses during hypoglycaemia induced by regular human insulin or a novel human analogue, insulin glargine.

AIM: Glargine, a product of recombinant technology, has different structural and physicochemical properties compared with native human insulin. We determined whether such differences are associated with alterations in the responses to hypoglycaemia induced by glargine. METHODS: Nineteen adults (six healthy and 13 with type 1 diabetes) underwent a 5-h hyperinsulinaemic (2 mU/kg/min(-1)) stepped hypoglycaemic clamps (hourly targets of 4.7, 4.2, 3.6, 3.1 and 2.5 mmol/l, respectively) on two occasions using intravenous infusion of regular human insulin or glargine, in random sequence. Hypoglycaemic symptoms, counter-regulatory hormones and glucose disposal rates were assessed at intervals throughout the clamps. A 1-week 'wash out' period was observed between studies. RESULTS: The peak total symptoms scores (mean +/- s.e.m.) at nadir blood glucose (2.5 mmol/1) were 18.83 +/- 2.68 (healthy) and 17.46 +/- 3.62 (diabetic) during regular insulin, and 18.50 +/- 3.20 (healthy) and 19.08 +/- 3.83 (diabetic) during glargine infusion. The peak epinephrine levels during hypoglycaemia were 767.8 +/- 140.4 pg/ml (regular insulin) and 608.8 +/- 129.9 pg/ml (glargine) among healthy subjects, and 332.5 +/- 54.8 pg/ml (regular insulin) and 321.8 +/- 67.4 pg/ml (glargine) in diabetic patients. Diabetic patients had blunted glucagon responses during hypoglycaemia with either insulin. Both insulins also elicited similar rates of glucose disposal. CONCLUSIONS: We conclude that insulin glargine and regular human insulin elicit comparable symptomatic and counter-regulatory hormonal responses during hypoglycaemia in healthy or diabetic subjects, and induce similar rates of glucose disposal. Since glargine is designed for subcutaneous (s.c.) use, it is possible (though unlikely) that our findings obtained using an intravenous protocol could differ from responses to hypoglycaemia induced by the s.c. route.

Pressure ulcer development in the VA: characteristics of nursing homes providing best care.

This study identifies structural characteristics of VA nursing homes that are associated with the best patient outcomes. We evaluated risk-adjusted rates of pressure ulcer development in VA nursing homes and related these rates to facility size, staffing patterns, teaching nursing home status, and rural versus urban locale. Higher rates of pressure ulcer development were seen among urban teaching nursing homes and among nursing homes associated with both larger and smaller VA hospitals. Staffing patterns had a complex association with pressure ulcer development, and smaller nursing home staffs were not clearly associated with higher rates. For multivariate modeling, only hospital size and staffing remained significant independent predictors of pressure ulcer development. These results emphasize that while structural characteristics of VA nursing homes can provide insights about care, improving the quality of care in this setting will require a much greater understanding of how nursing homes are organized to meet patient needs.

Data and information requirements for the Department of Veterans Affairs resource allocation systems.

The department of Veterans Affairs (VA) uses a global budgeting process to allocate congressionally appropriated resources to provide medical care to veterans. The Department of Veterans Affairs has developed this process to accommodate the effects of changes in pure inflation, workload, and cost per unit of work in forecasting operating dollars required for facility global budgets. In 1990, VA began shifting to a new method of allocating its global budget called Resource Planning and Management (RPM), based on a capitated system. Facilities receive resources according to their unit costs and the number and type of patients they are expected to serve. A key characteristic of any global budgeting information system is flexibility. The VA information system accesses the portion of each patients's care that is provided at every facility and aggregates this information across all facilities to create a single prorated patient record; the system reconstructs prior years of data into the new patient-centered format to forecast workload. No other health care system in the United States pays for and directly provides such a diverse set of services for such a large population as does VA. Nevertheless, many of the problems VA faces are similar to those of other providers and insurers.

Teaching and hospital production: the use of regression estimates.

Medicare's Prospective Payment System pays U.S. teaching hospitals for the indirect costs of medical education based on a regression coefficient in a cost function. In regression studies using health care data, it is common for explanatory variables to be measured imperfectly, yet the potential for measurement error is often ignored. In this paper, U.S. Department of Veterans Affairs data is used to examine issues of health care production estimation and the use of regression estimates like the teaching adjustment factor. The findings show that measurement error and persistent multicollinearity confound attempts to have a large degree of confidence in the precise magnitude of parameter estimates.

Hospital staffing adjustments under global budgeting.

The U.S. Department of Veterans Affairs operates a hospital system that distributes a national global budget to 159 hospital units. Over recent years, cost containment and downward budgetary pressures have affected hospital performance and the quality of care delivered in unknown ways. This article examines hospital staffing levels as potential performance measures. We first develop a regression model to estimate the number and types of clinical staff required to meet current inpatient workloads at VA medical centers. We are able to improve on previous analyses by employing better data on physicians and by evaluating the behavior of hospitals in consecutive years. Our findings provide managers of hospital systems with promising new approaches for comparing hospital production processes and more information on the effects of global budgeting on individual hospital staffing within systems.

Artificial heart and cardiac transplantation: report on the first European combined procedure.

It became necessary to perform a staged procedure by means of total artificial heart followed by cardiac transplantation in a 26-year-old, female patient. The Ellipsoidheart, as an artificial heart, fitted excellently in the chest without compromising the surrounding structures. As soon as the patient recovered with the artificial heart, a consecutive transplantation was performed. This first European clinical experience gained confidence and suggests applying more artificial hearts as a bridge towards transplantation.

Aphasia resulting from occlusion of the left anterior cerebral artery. Report of a case with an old infarct in the left Rolandic region.

A 62-year-old right-handed woman was admitted to the hospital with a cerebrovascular accident in the left hemisphere. She was aphasic as well as hemiplegic on the right. She had had a left cerebrovascular accident 18 years earlier that caused weakness in the right hand, but no grossly detectable speech problems. Autopsy disclosed an old infarct along the left Rolandic area, and a recent infarct in the territory of the left anterior cerebral artery. The clinical picture and pathologic changes are discussed in an attempt to relate the findings at autopsy to the recently developed aphasia.

Nonassociation of hyperamylasemia and prostatic disease.

The possible correlation of hyperamylasemia and prostatic disease was investigated in patients with benign prostatic hyperplasia, adenocarcinoma of the prostate, and in patients without clinical evidence of prostatic lesion. Our results indicate that prostatic lesions whether benign or malignant are not associated with either elevation of serum amylase or abnormal isozyme zymograms.