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Purpose Diffuse large B‑cell lymphoma (DLBCL) is an aggressive lymphoma subtype treated successfully with immunochemotherapy. However, there are conflicting data on the role and impact of consolidative radiation therapy (RT). The publication of the national evidence-based guideline on DLBCL prompted us to review relevant passages on radiation oncology. Methods The following article reviews the evidence and recommendations given in the current German evidence-based guideline on DLBCL regarding RT and summarizes pivotal aspects. Additional literature is presented to provide a comprehensive background for the published recommendations. Results RT shall be administered to all patients with localized positron emission tomography(PET)-positive residues after completion of immunochemotherapy and should use a dose of 30–40 Gray in normofractionation. For RT planning, PET information before and after immunochemotherapy shall be used, with either a PET-CT in the RT treatment position or an image fusion to the planning CT. Conformal techniques shall be used for target volume coverage, with a risk–benefit evaluation for the individual patient. Additionally, RT may be used in the treatment context of various subtypes of DLBCL as well as in the recurrent or refractory treatment situation. Conclusion RT remains an integral part of the treatment repertoire of DLBCL. With the use of PET-guided treatment, RT is indicated for patients with metabolically active tumors. In the context of the ongoing development of targeted therapies, new RT indications may evolve.

Background: Previous reviews indicated positive effects of resistance training (RT) on motor outcomes in Parkinson’s disease (PD). However, inconsistencies between the included studies exist, and non-motor outcomes have only scarcely been considered in a review on RT in PD. Objective: To analyze the RT effects on motor- and non-motor outcomes in PD patients compared to passive and physically active control groups (i.e., other structured physical interventions). Methods: We searched CENTRAL, MEDLINE, EMBASE, and CINAHL for randomized controlled trials of RT in PD. After identifying 18 studies, a meta-analysis was conducted for the outcomes muscle strength, motor impairment, freezing of gait (FoG), mobility and balance, quality of life (QoL), depression, cognition, and adverse events. Meta-analyses with random models were calculated using mean differences (MD) or standardized mean differences (SMD) with 95% confidence intervals (CI). Results: When comparing RT with passive control groups, the meta-analyses showed significant large effects on muscle strength (SMD = –0.84, 95% CI –1.29––0.39, p = 0.0003), motor impairment (SMD = –0.81, 95% CI –1.34––0.27, p = 0.003), mobility and balance (MD = –1.81, 95% CI –3.13––0.49, p = 0.007), and small significant effects on QoL (SMD = –0.48, 95% CI –0.86––0.10, p = 0.01). RT compared with physically active control groups reached no significant results for any outcome. Conclusions: RT improves muscle strength, motor impairment, mobility and balance, QoL, and depression in PD patients. However, it is not superior to other physically active interventions. Therefore, exercise is important for PD patients but according to this analysis, its type is of secondary interest.

Physical exercise is effective in managing Parkinson's disease (PD), but the relative benefit of different exercise types remains unclear.To compare the effects of different types of physical exercise in adults with PD on the severity of motor signs, quality of life (QoL), and the occurrence of adverse events, and to generate a clinically meaningful treatment ranking using network meta-analyses (NMAs).An experienced information specialist performed a systematic search for relevant articles in CENTRAL, MEDLINE, Embase, and five other databases to 17 May 2021. We also searched trial registries, conference proceedings, and reference lists of identified studies up to this date.We included randomized controlled trials (RCTs) comparing one type of physical exercise for adults with PD to another type of exercise, a control group, or both.Two review authors independently extracted data. A third author was involved in case of disagreements. We categorized the interventions and analyzed their effects on the severity of motor signs, QoL, freezing of gait, and functional mobility and balance up to six weeks after the intervention using NMAs. Two review authors independently assessed the risk of bias using the risk of bias 2 (RoB 2) tool and rated the confidence in the evidence using the CINeMA approach for results on the severity of motor signs and QoL. We consulted a third review author to resolve any disagreements. Due to heterogeneous reporting of adverse events, we summarized safety data narratively and rated our confidence in the evidence using the GRADE approach.We included 156 RCTs with a total of 7939 participants with mostly mild to moderate disease and no major cognitive impairment. The number of participants per study was small (mean 51, range from 10 to 474). The NMAs on the severity of motor signs and QoL included data from 71 (3196 participants), and 55 (3283 participants) trials, respectively. Eighty-five studies (5192 participants) provided safety data. Here, we present the main results. We observed evidence of beneficial effects for most types of physical exercise included in our review compared to a passive control group. The effects on the severity of motor signs and QoL are expressed as scores on the motor scale of the Unified Parkinson Disease Rating Scale (UPDRS-M) and the Parkinson's Disease Questionnaire 39 (PDQ-39), respectively. For both scales, higher scores denote higher symptom burden. Therefore, negative estimates reflect improvement (minimum clinically important difference: -2.5 for UPDRS-M and -4.72 for PDQ-39). Severity of motor signs The evidence from the NMA (71 studies; 3196 participants) suggests that dance has a moderate beneficial effect on the severity of motor signs (mean difference (MD) -10.32, 95% confidence interval (CI) -15.54 to -4.96; high confidence), and aqua-based, gait/balance/functional, and multi-domain training might have a moderate beneficial effect on the severity of motor signs (aqua-based: MD -7.77, 95% CI -13.27 to -2.28; gait/balance/functional: MD -7.37, 95% CI -11.39 to -3.35; multi-domain: MD -6.97, 95% CI -10.32 to -3.62; low confidence). The evidence also suggests that mind-body training and endurance training might have a small beneficial effect on the severity of motor signs (mind-body: MD -6.57, 95% CI -10.18 to -2.81; endurance: MD -6.43, 95% CI -10.72 to -2.28; low confidence). Flexibility training might have a trivial or no effect on the severity of motor signs (MD 2.01, 95% CI -4.82 to 8.98; low confidence). The evidence is very uncertain about the effects of strength/resistance training and "Lee Silverman Voice training BIG" (LSVT BIG) on the severity of motor signs (strength/resistance: MD -6.97, 95% CI -11.93 to -2.01; LSVT BIG: MD -5.49, 95% CI -14.74 to 3.62; very low confidence). Quality of life The evidence from the NMA (55 studies; 3283 participants) suggests that aqua-based training probably has a large beneficial effect on QoL (MD -14.98, 95% CI -23.26 to -6.52; moderate confidence). The evidence also suggests that endurance training might have a moderate beneficial effect, and that gait/balance/functional and multi-domain training might have a small beneficial effect on QoL (endurance: MD -9.16, 95% CI -15.68 to -2.82; gait/balance/functional: MD -5.64, 95% CI -10.04 to -1.23; multi-domain: MD -5.29, 95% CI -9.34 to -1.06; low confidence). The evidence is very uncertain about the effects of mind-body training, gaming, strength/resistance training, dance, LSVT BIG, and flexibility training on QoL (mind-body: MD -8.81, 95% CI -14.62 to -3.00; gaming: MD -7.05, 95% CI -18.50 to 4.41; strength/resistance: MD -6.34, 95% CI -12.33 to -0.35; dance: MD -4.05, 95% CI -11.28 to 3.00; LSVT BIG: MD 2.29, 95% CI -16.03 to 20.44; flexibility: MD 1.23, 95% CI -11.45 to 13.92; very low confidence). Adverse events Only 85 studies (5192 participants) provided some kind of safety data, mostly only for the intervention groups. No adverse events (AEs) occurred in 40 studies and no serious AEs occurred in four studies. AEs occurred in 28 studies. The most frequently reported events were falls (18 studies) and pain (10 studies). The evidence is very uncertain about the effect of physical exercise on the risk of adverse events (very low confidence). Across outcomes, we observed little evidence of differences between exercise types.We found evidence of beneficial effects on the severity of motor signs and QoL for most types of physical exercise for people with PD included in this review, but little evidence of differences between these interventions. Thus, our review highlights the importance of physical exercise regarding our primary outcomes severity of motor signs and QoL, while the exact exercise type might be secondary. Notably, this conclusion is consistent with the possibility that specific motor symptoms may be treated most effectively by PD-specific programs. Although the evidence is very uncertain about the effect of exercise on the risk of adverse events, the interventions included in our review were described as relatively safe. Larger, well-conducted studies are needed to increase confidence in the evidence. Additional studies recruiting people with advanced disease severity and cognitive impairment might help extend the generalizability of our findings to a broader range of people with PD.

Herein we describe the first examples of isolable electron‐precise diboranes(4) that bear azide moieties: the acyclic 1,2‐diazido‐1,2‐bis(dimethylamino)diborane(4) and the cyclic 1,4‐diaryl‐2,3‐diazido‐1,4‐diaza‐2,3‐diborinines (aryl=mesityl, 2,6‐xylyl, 4‐tolyl). The reported examples are not only stable enough to be observed and isolated (putative transient diborane(4) azides previously reported by our group spontaneously decompose even below room temperature), but some of them are even robust enough to undergo controlled pyrolysis without explosive decomposition at temperatures well above 100 °C. In two cases, the controlled pyrolysis allows the isolation of complex diazaboretidines, which are the apparent dimerization products of endocyclic boryl‐iminoboranes., Potentially explosive yet mild‐mannered! The synthesis and reactivity of diamino‐substituted diborane(4) diazides, the first diborane(4) azides, is reported. Despite the presence of energetic and oxidizing azide groups and of reactive B−B bonds, they are astonishingly robust. The species do not decompose below 100 °C. Two diazides could be pyrolyzed in a controlled manner to diazadiboretidines, the dimerization product of transient iminoboranes.

Background Diffuse large B‐cell lymphoma (DLBCL) is an aggressive cancer of the lymphatic system. About 30% to 40% of people with DLBCL experience relapse and 10% are refractory to first‐line treatment usually consisting of R‐CHOP chemotherapy. Of those eligible for second‐line treatment, commonly consisting of salvage chemotherapy followed by autologous stem‐cell transplantation (ASCT), around 50% experience relapse. With a median overall survival of less than six to 12 months, the prognosis of individuals who relapse or are refractory (r/r) to advanced lines of treatment or of those who are ineligible for ASCT, is very poor. With the introduction of chimeric antigen receptor (CAR) T‐cell therapy, a novel treatment option for these people is available. Objectives To assess the benefits and harms of chimeric antigen receptor (CAR) T‐cell therapy for people with relapsed or refractory (r/r) DLBCL. Search methods An experienced information specialist performed a systematic database search for relevant articles on CENTRAL, MEDLINE and Embase until September 11th, 2020. We also searched trial registries and reference lists of identified studies up to this date. All search results were screened by two authors independently and a third author was involved in case of discrepancies. Selection criteria We included prospectively planned trials evaluating CAR T‐cell therapy for people with r/r DLBCL. We had planned to include randomised controlled trials (RCTs) and we flexibly adapted eligibility criteria to the most reliable study designs available. We excluded studies involving fewer than 10 participants with r/r DLBCL and studies with a proportion of participants with r/r DLBCL below 70%, unless data were reported separately for this subgroup. Data collection and analysis Two review authors extracted data and performed risk of bias ratings independently. A third author was involved in case of disagreements. As our search did not yield any completed RCTs, prospective controlled non‐randomised studies of interventions (NRSIs) or prospective observational studies with a control group, we did not meta‐analyse data and reported all results narratively. We adopted the GRADE approach to assess the certainty of the evidence for prioritised outcomes. Main results We identified 13 eligible uncontrolled studies evaluating a single or multiple arms of CAR T‐cell therapies. We also identified 38 ongoing studies, including three RCTs. Ten studies are awaiting classification due to completion with no retrievable results data or insufficient data to justify inclusion. The mean number of participants enrolled, treated with CAR T‐cell therapy and evaluated in the included studies were 79 (range 12 to 344; data unavailable for two studies), 61 (range 12 to 294; data unavailable for one study) and 52 (range 11 to 256), respectively. Most studies included people with r/r DLBCL among people with other haematological B‐cell malignancies. Participants had received at least a median of three prior treatment lines (data unavailable for four studies), 5% to 50% had undergone ASCT (data unavailable for five studies) and, except for two studies, 3% to 18% had undergone allogenic stem‐cell transplantation (data unavailable for eight studies). The overall risk of bias was high for all studies, in particular, due to incomplete follow‐up and the absence of blinding. None of the included studies had a control group so that no adequate comparative effect measures could be calculated. The duration of follow‐up varied substantially between studies, in particular, for harms. Our certainty in the evidence is very low for all outcomes. Overall survival was reported by eight studies (567 participants). Four studies reported survival rates at 12 months which ranged between 48% and 59%, and one study reported an overall survival rate of 50.5% at 24 months. The evidence is very uncertain about the effect of CAR T‐cell therapy on overall survival. Two studies including 294 participants at baseline and 59 participants at the longest follow‐up (12 months or 18 months) described improvements of quality of life measured with the EuroQol 5‐Dimension 5‐Level visual analogue scale (EQ‐5D‐5L VAS) or Function Assessment of Cancer Therapy‐Lymphoma (FACT‐Lym). The evidence is very uncertain about the effect of CAR T‐cell therapy on quality of life. None of the studies reported treatment‐related mortality. Five studies (550 participants) reported the occurrence of adverse events among participants, ranging between 99% and 100% for any grade adverse events and 68% to 98% for adverse events grade ≥ 3. In three studies (253 participants), 56% to 68% of participants experienced serious adverse events, while in one study (28 participants), no serious adverse events occurred. CAR T‐cell therapy may increase the risk of adverse events and serious adverse events but the evidence is very uncertain about the exact risk. The occurrence of cytokine release syndrome (CRS) was reported in 11 studies (675 participants) under use of various grading criteria. Five studies reported between 42% and 100% of participants experiencing CRS according to criteria described in Lee 2014. CAR T‐cell therapy may increase the risk of CRS but the evidence is very uncertain about the exact risk. Nine studies (575 participants) reported results on progression‐free survival, disease‐free survival or relapse‐free survival. Twelve‐month progression‐free survival rates were reported by four studies and ranged between 44% and 75%. In one study, relapse‐free survival remained at a rate of 64% at both 12 and 18 months. The evidence is very uncertain about the effect of CAR T‐cell therapy on progression‐free survival. Thirteen studies (620 participants) provided data on complete response rates. At six months, three studies reported complete response rates between 40% and 45%. The evidence is very uncertain about the effect of CAR T‐cell therapy on complete response rates. Authors' conclusions The available evidence on the benefits and harms of CAR T‐cell therapy for people with r/r DLBCL is limited, mainly because of the absence of comparative clinical trials. The results we present should be regarded in light of this limitation and conclusions should be drawn very carefully. Due to the uncertainty in the current evidence, a large number of ongoing investigations and a risk of substantial and potentially life‐threatening complications requiring supplementary treatment, it is critical to continue evaluating the evidence on this new therapy.

We derive and discuss the implications of massive spin-2 fields as possible extensions of the standard theory of gravity, general relativity, in the spirit of extension of the standard model of particle physics. We give a thorough introduction to the topic of massive gravity from the point of view of bi- or multi-metric extensions of general relativity, focussing on the bimetric case in the phenomenological considerations. Furthermore, known shortcomings and benefits of such models are discussed. From this discussion it is evident that the parameter regime of interest is mostly that of very small spin-2 masses, such that effects on galactic and extra-galactic length scales are expected. On these grounds, we investigate the dynamics of spiral galaxies in the form of rotation curves, from which we derive constraints on the model’s parameter space. Moreover, we discuss the modifications of gravitational lensing by galaxy clusters, which strongly constrain these parameters. We also highlight how these modifications could explain tentative anomalies in the observations of such systems. Finally, we make use of the recent detection and conformation of gravitational waves. If more than one spin-2 field is present, they are expected to mix dynamically in close analogy to the oscillation of neutrino flavours. This observation is confirmed quantitatively, and subsequently used to derive new constraints on the allowed masses and mixings of the two tensors. To this end, we employ both the available data as well as a future, hypothetical sample of many such signals and their distribution as a function of the cosmological redshift. We conclude our discussion with another critical contemplation of the current status and provide an outlook onto possible ultraviolet completions.

Particle therapy (PT) with scanned carbon ions has been shown to improve the treatment of stage IV lung cancer patients through reduced dose exposure of critical organs. In order to maximize this effect, the application of intensity modulated particle therapy (IMPT) is needed. However, PT is particularly susceptible to internal dose gradients due to its range dependence. This challenge is exacerbated in the presence of organ motion. Both, motion and internal dose gradients, can be addressed by dedicated robust 4D optimization strategies. In addition, as IMPT needs congruent target volumes, only robust 4D optimization can incorporate field-specific range uncertainties and motion-induced range changes. Hence, a ’worst-case’ method was implemented into GSI’s in-house treatment planning system TRiP4D and adapted for different 4D optimization strategies, accounting for setup and range uncertainties. The uncertainty scenarios of robust optimization increase the required computer memory, especially when also motion states are explicitly considered, as for robust 4D ITV optimization. Several strategies to reduce problem size and to increase the computation speed were implemented and tested, such as splitting the optimization matrix by dose contribution or randomized voxel subsampling. Plan robustness was tested by performing robustness analysis, where dose distributions were calculated for a variety of uncertainty scenarios. By creating the superposition of patient setup errors with particle range changes, uncertainty scenarios beyond the ones already used in the optimization were tested. In a patient study with 8 complex lung cancer patients, it was possible to increase plan robustness in the majority of patients using robust optimization. For conventional optimization, especially the dose volume exposure of the smaller airways (SA) became a limiting factor. Using the same 4D ITV planning strategy but with robust optimization enabled the OAR constraint for the SA to be fulfilled in 98.8 % of the cases, up from 79.8 % for conventional optimization. It is to note, that this increase in robustness could mean sacrificing target coverage in some patients. Furthermore, a robust implementation of conformal 4D optimization was developed, based on a library of treatment plans for each motion phase of a 4DCT. The reduction of irradiated volume considerably improved OAR exposure, but increased the need for robust optimization even further in order to maintain robustness against deviations of the delivered dose distribution from the planned dose distribution. For a lung cancer patient with large tumor motion, the robust conformal 4D optimization method could be shown to generate treatment plans with increased robustness against range and setup errors. As a result of the increased robustness, target coverage could be increased and dose exposure to the OARs could be decreased at the same time. In conclusion, both robust optimization methods for 4D treatment planning in PT yield promising results, generating new options for robust, safe intensity modulated particle therapy and thus beneficial treatment plans for lung cancer patients.

Elementar fur eine Tatigkeit als Fuhrungskraft sind Kenntnisse im Arbeitsrecht . Im Folgenden werden nach einem kurzen Uberblick uber sonstige Beendigungstatbestande die Voraussetzungen wirksamer Kundigungen (ordentlich und auserordentlich) und im Rahmen dessen von Abmahnungen dargestellt und erlautert. In der Praxis einer Fuhrungskraft lasst sich die Anwendung der Instrumente Abmahnung und Kundigung trotz vorgehend geschilderter Moglichkeiten der Konfliktbearbeitung ( 7 Kap. 9 ) im Vorfeld nicht vermeiden oder gar ausschliesen. Nicht zuletzt hat diese Thematik vor dem Hintergrund eines sich verscharfenden Wettbewerbs auch enorme wirtschaftliche Bedeutung. Dabei sind die Anforderungen an die Wirksamkeit einer Abmahnung und arbeitgeberseitigen Kundigung als nicht gering anzusehen. Da die Nichteinhaltung der zwingenden Voraussetzungen uberwiegend zur Unwirksamkeit einer ausgesprochenen Abmahnung und Kundigung fuhrt, ist genaue Kenntnis und penible Einhaltung der Vorschriften erforderlich.

As a toy model for the capacity problem in quantum information theory we investigate finite and asymptotic regularizations of the maximum pure-state input-output fidelity $F(\cal N$) of a general quantum channel $\cal N$. We show that the asymptotic regularization $\tilde F(\cal N$) is lower bounded by the maximum output $\infty$-norm $\nu_\infty(\cal N)$ of the channel. For $\cal N$ being a Pauli channel we find that both quantities are equal., Comment: 5 pages, 3 figures

Der wesentliche Garant fur die Pflegequalitat im Krankenhaus sind ausreichende und qualifizierte Pflegefachpersonen. Dies muss uber die DRG-Finanzierung gewahrleistet werden. Hier besteht, trotz aktueller Verbesserungen, nach wie vor deutlicher Handlungsbedarf, den es zu erbringen gilt. Aus Sicht des Deutschen Pflegerats e.V. (DPR) ergeben sich dabei vor allem drei Regelungsbedarfe, die umgesetzt werden mussen. Hierauf wird in diesem Kapitel eingegangen.

Deutschlands Krankenhauser und Pflegeeinrichtungen benotigen dringend mehr Personal. So geht der Pflegebevollmachtigte der Bundesregierung, Karl-Josef Laumann, fur die nachsten 25 Jahre da-von aus, dass wir jedes Jahr 20.000 zusatzliche Pflegekrafte mehr benotigen, allein um die jahrlich um 2 bis 3% steigende Zahl der Pflegebedurftigen versorgen zu konnen.

Die derzeitige Krankenhausfinanzierung stellt nicht sicher, dass ausreichend Pflegefachpersonen fur die Patientenversorgung zur Verfugung stehen. Dieser Mangel besteht seit langem, fuhrt zu einer Gefahrdung der Patientenversorgung, schadet der Attraktivitat des Berufes und lasst zugleich die Kosten steigen.

Staatssekretar Karl-Josef Laumann, Pflegebevollmachtigter der Bundesregierung, hat gemeinsam mit dem Institut fur Arbeitsmarkt- und Berufsforschung der Bundesagentur fur Arbeit (IAB) in Berlin die Studie „Was man in den Pflegeberufen in Deutschland verdient“ vorgestellt.

vom Morgenstern

Physics in medicine and biology 66(23), 235004 (2021). doi:10.1088/1361-6560/ac36e7, Published by IOP Publ., Bristol