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Modulation Transfer Function (MTF) is an important image quality metric. Traditional displays generate images on a flat display, whereas Near‐Eye‐Displays (NEDs) project virtual images with amplitude and wave‐front phase information. Poorly designed NED MTF test systems can introduce uncorrectable measurement errors, in contrast to well‐designed systems with aberration‐free optical performance.

Studien belegen einen gleichbleibend hohen Anteil von ca. 10–20 % unzufriedener Patienten nach Implantation einer Knietotalendoprothese (KTEP). In Anbetracht der Tatsache, dass nur ca. 15 % der Patienten eine tatsächlich gerade Beinachse und horizontale Gelenklinie aufweisen, wird deutlich, dass das klassische mechanische Alignment in vielen Fällen eine Veränderung der natürlichen Achsverhältnisse mit konsekutiven Auswirkungen auf die Weichteilspannung bewirkt. Vor diesem Hintergrund rücken zunehmend individualisierte Versorgungsstrategien in den Fokus, deren Ziel eine Rekonstruktion der natürlichen Kniegelenkskinematik ist. Die kürzlich veröffentlichte CPAK(Coronal Plane Alignment of the Knee)-Klassifikation definiert 9 konstitutionelle Kniephänotypen anhand der nativen Achsverhältnisse in der Frontalebene und der Neigung der Gelenklinie. Die Kenntnis des individuellen CPAK-Typs ist essenziell für die Anwendung moderner Alignmentstrategien, welche auf eine Rekonstruktion der individuellen Achsverhältnisse, der Gelenklinie sowie der individuellen Weichteilspannung zielen. Der Einsatz roboterassistierter Verfahren ist eine entscheidende Komponente für die präzise Umsetzung dieser individuellen Versorgungsstrategien. Basierend auf der Erfassung der knöchernen Anatomie und der intraoperativen Visualisierung der Weichteilspannung kann die Auswirkung der Komponentenausrichtung auf die Balancierung in Echtzeit simuliert werden und der operative Plan mit einer hohen Präzision ausgeführt werden. Dieser Beitrag soll einen Überblick über die CPAK-Klassifikation konstitutioneller Kniephänotypen und alternative Alignmentstrategien vermitteln. Abschließend wird ein Ansatz für die praktische Anwendung der CPAK-Klassifikation mithilfe roboterassistierter Technologien beschrieben.

ABSTRACTThe number of U.S. prisoners with minor children has increased dramatically in recent decades. Although the quality of inmate-child communication is positively associated with individual and familial outcomes, innovative programming for incarcerated parents is limited. This mixed methods study explored the initial delivery to incarcerated fathers of a letter-writing intervention developed for and previously used with incarcerated mothers. Pre- to post-intervention measures of parental stress, communication, and relationships with caregivers were tested with the Wilcoxon Signed Rank test. Focus groups were conducted post-intervention to explore perceptions of parental challenges and the intervention. Participants experienced significant improvements in communication and caregiver relations, but not in parental stress. Themes from qualitative analysis highlighted important barriers to communication, positive attributes of the intervention—including structured prompts, outside facilitators and peer support—and improved emotional responses and parental identity among participants. The discussion explores ways to build on this successful delivery to incarcerated fathers.

IMPORTANCE: Chronic pain is debilitating and profoundly affects health-related quality of life. Spinal cord stimulation (SCS) is a well-established therapy for chronic pain; however, SCS has been limited by the inability to directly measure the elicited neural response, precluding confirmation of neural activation and continuous therapy. A novel SCS system measures the evoked compound action potentials (ECAPs) to produce a real-time physiological closed-loop control system. OBJECTIVE: To determine whether ECAP-controlled, closed-loop SCS is associated with better outcomes compared with fixed-output, open-loop SCS at 24 months following implant. DESIGN, SETTING, AND PARTICIPANTS: The Evoke study was a double-blind, randomized, controlled, parallel arm clinical trial with 36 months of follow-up. Participants were enrolled from February 2017 to 2018, and the study was conducted at 13 US investigation sites. SCS candidates with chronic, intractable back and leg pain refractory to conservative therapy, who consented, were screened. Key eligibility criteria included overall, back, and leg pain visual analog scale score of 60 mm or more; Oswestry Disability Index score of 41 to 80; stable pain medications; and no previous SCS. Analysis took place from October 2020 to April 2021. INTERVENTIONS: ECAP-controlled, closed-loop SCS was compared with fixed-output, open-loop SCS. MAIN OUTCOMES AND MEASURES: Reported here are the 24-month outcomes of the trial, which include all randomized patients in the primary and safety analyses. The primary outcome was a reduction of 50% or more in overall back and leg pain assessed at 3 and 12 months (previously published). RESULTS: Of 134 randomized patients, 65 (48.5%) were female and the mean (SD) age was 55.2 (10.6) years. At 24 months, significantly more closed-loop than open-loop patients were responders (≥50% reduction) in overall pain (53 of 67 [79.1%] in the closed-loop group; 36 of 67 [53.7%] in the open-loop group; difference, 25.4% [95% CI, 10.0%-40.8%]; P = .001). There was no difference in safety profiles between groups (difference in rate of study-related adverse events: 6.0 [95% CI, −7.8 to 19.7]). Improvements were also observed in health-related quality of life, physical and emotional functioning, and sleep, in parallel with opioid reduction or elimination. Objective neurophysiological measurements substantiated the clinical outcomes and provided evidence of activation of inhibitory pain mechanisms. CONCLUSIONS AND RELEVANCE: ECAP-controlled, closed-loop SCS, which elicited a more consistent neural response, was associated with sustained superior pain relief at 24 months, consistent with the 3- and 12-month outcomes.

NP105–113-B*07:02-specific CD8+T cell responses are considered among the most dominant in SARS-CoV-2-infected individuals. We found strong association of this response with mild disease. Analysis of NP105–113-B*07:02-specific T cell clones and single-cell sequencing were performed concurrently, with functional avidity and antiviral efficacy assessed using an in vitro SARS-CoV-2 infection system, and were correlated with T cell receptor usage, transcriptome signature and disease severity (acute n= 77, convalescent n= 52). We demonstrated a beneficial association of NP105–113-B*07:02-specific T cells in COVID-19 disease progression, linked with expansion of T cell precursors, high functional avidity and antiviral effector function. Broad immune memory pools were narrowed postinfection but NP105–113-B*07:02-specific T cells were maintained 6 months after infection with preserved antiviral efficacy to the SARS-CoV-2 Victoria strain, as well as Alpha, Beta, Gamma and Delta variants. Our data show that NP105–113-B*07:02-specific T cell responses associate with mild disease and high antiviral efficacy, pointing to inclusion for future vaccine design.

AbstractThis interview-article is a commentary on some of the early reverberations of Covid-19 on the fashion industry. It introduces R.I.(a)P., a work by fashion designer and professor Wowo Kraus to pull focus on some of the immediate industry reactions, and the underlying ambiguity of fashion, branding and death. Fashion evades death, just as death continues to be tabooed in global Western culture. Through its evocative aesthetic and materiality R.I.(a)P. can illuminate some of the blind spots of this industry. Here Kraus talks about the ideas and intricate making processes behind his work.

Primary immunodeficiencies in the costimulatory molecule CD27 and its ligand, CD70, predispose for pathologies of uncontrolled Epstein-Barr virus (EBV) infection in nearly all affected patients. We demonstrate that both depletion of CD27+ cells and antibody blocking of CD27 interaction with CD70 cause uncontrolled EBV infection in mice with reconstituted human immune system components. While overall CD8+ T-cell expansion and composition are unaltered after antibody blocking of CD27, only some EBV-specific CD8+ T-cell responses, exemplified by early lytic EBV antigen BMLF1-specific CD8+ T cells, are inhibited in their proliferation and killing of EBV-transformed B cells. This suggests that CD27 is not required for all CD8+ T-cell expansions and cytotoxicity but is required for a subset of CD8+ T-cell responses that protect us from EBV pathology.

Primary immunodeficiencies in the costimulatory molecule CD27 and its ligand, CD70, predispose for pathologies of uncontrolled Epstein-Barr virus (EBV) infection in nearly all affected patients. We demonstrate that both depletion of CD27+cells and antibody blocking of CD27 interaction with CD70 cause uncontrolled EBV infection in mice with reconstituted human immune system components. While overall CD8+T-cell expansion and composition are unaltered after antibody blocking of CD27, only some EBV-specific CD8+T-cell responses, exemplified by early lytic EBV antigen BMLF1-specific CD8+T cells, are inhibited in their proliferation and killing of EBV-transformed B cells. This suggests that CD27 is not required for all CD8+T-cell expansions and cytotoxicity but is required for a subset of CD8+T-cell responses that protect us from EBV pathology.

IMPORTANCE: Many patients with diabetic peripheral neuropathy experience chronic pain and inadequate relief despite best available medical treatments. OBJECTIVE: To determine whether 10-kHz spinal cord stimulation (SCS) improves outcomes for patients with refractory painful diabetic neuropathy (PDN). DESIGN, SETTING, AND PARTICIPANTS: The prospective, multicenter, open-label SENZA-PDN randomized clinical trial compared conventional medical management (CMM) with 10-kHz SCS plus CMM. Participants with PDN for 1 year or more refractory to gabapentinoids and at least 1 other analgesic class, lower limb pain intensity of 5 cm or more on a 10-cm visual analogue scale (VAS), body mass index (calculated as weight in kilograms divided by height in meters squared) of 45 or less, hemoglobin A1c (HbA1c) of 10% or less, daily morphine equivalents of 120 mg or less, and medically appropriate for the procedure were recruited from clinic patient populations and digital advertising. Participants were enrolled from multiple sites across the US, including academic centers and community pain clinics, between August 2017 and August 2019 with 6-month follow-up and optional crossover at 6 months. Screening 430 patients resulted in 214 who were excluded or declined participation and 216 who were randomized. At 6-month follow-up, 187 patients were evaluated. INTERVENTIONS: Implanted medical device delivering 10-kHz SCS. MAIN OUTCOMES AND MEASURES: The prespecified primary end point was percentage of participants with 50% pain relief or more on VAS without worsening of baseline neurological deficits at 3 months. Secondary end points were tested hierarchically, as prespecified in the analysis plan. Measures included pain VAS, neurological examination, health-related quality of life (EuroQol Five-Dimension questionnaire), and HbA1c over 6 months. RESULTS: Of 216 randomized patients, 136 (63.0%) were male, and the mean (SD) age was 60.8 (10.7) years. Additionally, the median (interquartile range) duration of diabetes and peripheral neuropathy were 10.9 (6.3-16.4) years and 5.6 (3.0-10.1) years, respectively. The primary end point assessed in the intention-to-treat population was met by 5 of 94 patients in the CMM group (5%) and 75 of 95 patients in the 10-kHz SCS plus CMM group (79%; difference, 73.6%; 95% CI, 64.2-83.0; P < .001). Infections requiring device explant occurred in 2 patients in the 10-kHz SCS plus CMM group (2%). For the CMM group, the mean pain VAS score was 7.0 cm (95% CI, 6.7-7.3) at baseline and 6.9 cm (95% CI, 6.5-7.3) at 6 months. For the 10-kHz SCS plus CMM group, the mean pain VAS score was 7.6 cm (95% CI, 7.3-7.9) at baseline and 1.7 cm (95% CI, 1.3-2.1) at 6 months. Investigators observed neurological examination improvements for 3 of 92 patients in the CMM group (3%) and 52 of 84 in the 10-kHz SCS plus CMM group (62%) at 6 months (difference, 58.6%; 95% CI, 47.6-69.6; P < .001). CONCLUSIONS AND RELEVANCE: Substantial pain relief and improved health-related quality of life sustained over 6 months demonstrates 10-kHz SCS can safely and effectively treat patients with refractory PDN. TRIAL REGISTRATION: ClincalTrials.gov Identifier: NCT03228420

The hemodialysis (HD) session per se is a catabolic event contributing to protein–energy wasting via several mechanisms including nutrient losses. Amino acids (AAs) losses in the dialysate are estimated from 6 to 10 g per treatment. The HD patient plasma AA concentration is usually lower than in normal subjects. This is even more marked in patients with long dialysis vintage or malnutrition.

And nothing has changed since then, as the only two nuclear plants now under construction in the U.S., in Georgia, are projected to cost at least $30 billion - more than double the original estimate - and are more than six years behind schedule. Derek Thompson makes a number of insightful arguments about the decline in American progress. Front Letters Derek Thompson's conclusion that societal progress depends on trust is profound and should be shouted from the rooftops. [Extracted from the article]

Checkpoint inhibitors and adoptive cell therapy provide promising options for treating solid cancers such as HBV-related HCC, but they have limitations. We tested the potential to combine advantages of each approach, genetically reprogramming T cells specific for viral tumor antigens to overcome exhaustion by down-modulating the co-inhibitory receptor PD-1. We developed a novel lentiviral transduction protocol to achieve preferential targeting of endogenous or TCR-redirected, antigen-specific CD8 T cells for shRNA knockdown of PD-1 and tested functional consequences for antitumor immunity. Antigen-specific and intrahepatic CD8 T cells transduced with lentiviral (LV)-shPD-1 consistently had a marked reduction in PD-1 compared to those transduced with a control lentiviral vector. PD-1 knockdown of human T cells rescued antitumor effector function and promoted killing of hepatoma cells in a 3D microdevice recapitulating the pro-inflammatory PD-L1hiliver microenvironment. However, upon repetitive stimulation, PD-1 knockdown drove T cell senescence and induction of other co-inhibitory pathways. We provide the proof of principle that T cells with endogenous or genetically engineered specificity for HBV-associated HCC viral antigens can be targeted for functional genetic editing. We show that PD-1 knockdown enhances immediate tumor killing but is limited by compensatory engagement of alternative co-inhibitory and senescence program upon repetitive stimulation.

ABSTRACTThere is a scarcity of studies exploring treatment modalities specifically designed for the incarcerated mother. This paper presents findings from a program designed to help incarcerated mothers develop their ability to communicate and subsequently bond with their children by engaging in group discussions during a letter-writing process. Using mixed research methods from 16 incarcerated mothers, the participants reported (1) gaining insight into personal emotions and strengths around parenting, (2) strengthening of positive parenting strategies, (3) increasing ability to empathize with their children, and (4) increasing tools to enhance communication. The quantitative data showed significant improvement in the areas of seeing themselves as better parents and decreasing anxiety around parenting issues. The participants gave feedback for models developed for incarcerated mothers.

ABSTRACTThis study expands the literature of online human diversity courses in social work by comparing the effectiveness of these courses to face-to-face instruction. To measure effectiveness, pre- and posttests were completed by 117 students. The instrument used measured awareness of and ability to recognize cultural diversity and oppression and the level of belief that our society is just. The findings suggest that online and face-to-face students showed an increase in their awareness of diversity and oppression issues with little to no significant difference between the two groups. Although not statistically significant, the online students’ belief in a just world decreased, whereas their face-to-face counterparts showed an increase, which was an unexpected finding. Implications for online social work classes are discussed.

Ongoing clinical trials explore T cell receptor (TCR) gene therapy as a treatment option for cancer, but responses in solid tumors are hampered by the immunosuppressive microenvironment. The production of TCR gene-engineered T cells requires full T cell activation in vitro, and it is currently unknown whether in vivointeractions with conventional dendritic cells (cDCs) regulate the accumulation and function of engineered T cells in tumors. Using the B16 melanoma model and the inducible depletion of CD11c+cells in CD11c.diphtheria toxin receptor (DTR) mice, we analyzed the interaction between tumor-resident cDCs and engineered T cells expressing the melanoma-specific TRP-2 TCR. We found that depletion of CD11c+cells triggered the recruitment of cross-presenting cDC1 into the tumor and enhanced the accumulation of TCR-engineered T cells. We show that the recruited tumor cDCs present melanoma tumor antigen, leading to enhanced activation of TCR-engineered T cells. In addition, detailed analysis of the tumor myeloid compartment revealed that the depletion of a population of DT-sensitive macrophages can contribute to the accumulation of tumor-infiltrating T cells. Together, these data suggest that the relative frequency of tumor-resident cDCs and macrophages may impact the therapeutic efficacy of TCR gene therapy in solid tumors.

Energy storage systems for powering electronic medical implants and sensors are essentially based on conventional electrode materials and electrolytes. Because of their toxicity, these battery systems need special encapsulation, which leads to bulky devices. Batteries based on biocompatible electrodes and electrolytes overcome these limitations and hold promise as viable alternatives for powering medical implants and devices. The present review aims at giving an overview of possible battery systems and current performance. It also gives a summary of battery architectures and their fabrication, with a focus on potential miniaturization. Advances in biocompatible batteries are expected to have not only a large impact on electronic medical implants and point-of-care monitoring systems, but also for environmental sensing and transient electronics.This review highlights recent advances and performances of biocompatible batteries, which are expected to play increasingly important roles in medical electronic implantable devices and point-of-care systems, but also for environmental sensing and transient electronics.

Laura Weinstein writes that "boys who fall behind in school can find great careers as mechanics, patrol officers, and wind-turbine technicians." Front THE COMMONS DISCUSSION & DEBATE Letters Speaking as a 75-year-old man, I completely agree with Richard Reeves's "Redshirt the Boys." William McClanahan San Francisco, Calif. RICHARD V. REEVES REPLIES: I'm grateful to all those who took the time to comment on my essay. [Extracted from the article]

Supplemental Digital Content is available in the text.

AbstractInternational social work is caused through current confrontations. It deals with the consequences of colonization, de-colonization, globalization and indigenization. This requires a “border thinking” and new focus on local and indigenous knowledge. Taking the colonial wounds as a chance, the creation of a diverse world based on older forms of knowledge would be imaginable. Especially, social movements of population that have been marginalized in colonialism are seen as subject of hope. Our aim is to encourage the re-appropriation and re-interpretation of concepts and content from repressed and forgotten traditions and an interculturalism as an exchange and negotiation. Both recognize local indigenous knowledge and transform this into a practice of international social work; this is the main thesis of our article.

Heterozygous CTLA-4 deficiency has been reported as a monogenic cause of common variable immune deficiency with features of immune dysregulation. Direct mutation in CTLA-4 leads to defective regulatory T-cell (Treg) function associated with impaired ability to control levels of the CTLA-4 ligands, CD80 and CD86. However, additional mutations affecting the CTLA-4 pathway, such as those recently reported for LRBA, indirectly affect CTLA-4 expression, resulting in clinically similar disorders. Robust phenotyping approaches sensitive to defects in the CTLA-4 pathway are therefore required to inform understanding of such immune dysregulation syndromes. Here, we describe assays capable of distinguishing a variety of defects in the CTLA-4 pathway. Assessing total CTLA-4 expression levels was found to be optimal when restricting analysis to the CD45RA−Foxp3+fraction. CTLA-4 induction following stimulation, and the use of lysosomal-blocking compounds, distinguished CTLA-4 from LRBA mutations. Short-term T-cell stimulation improved the capacity for discriminating the Foxp3+Treg compartment, clearly revealing Treg expansions in these disorders. Finally, we developed a functionally orientated assay to measure ligand uptake by CTLA-4, which is sensitive to ligand-binding or -trafficking mutations, that would otherwise be difficult to detect and that is appropriate for testing novel mutations in CTLA-4 pathway genes. These approaches are likely to be of value in interpreting the functional significance of mutations in the CTLA-4 pathway identified by gene-sequencing approaches.

Heterozygous CTLA-4 deficiency has been reported as a monogenic cause of common variable immune deficiency with features of immune dysregulation. Direct mutation in CTLA-4 leads to defective regulatory T-cell (Treg) function associated with impaired ability to control levels of the CTLA-4 ligands, CD80 and CD86. However, additional mutations affecting the CTLA-4 pathway, such as those recently reported for LRBA, indirectly affect CTLA-4 expression, resulting in clinically similar disorders. Robust phenotyping approaches sensitive to defects in the CTLA-4 pathway are therefore required to inform understanding of such immune dysregulation syndromes. Here, we describe assays capable of distinguishing a variety of defects in the CTLA-4 pathway. Assessing total CTLA-4 expression levels was found to be optimal when restricting analysis to the CD45RA−Foxp3+ fraction. CTLA-4 induction following stimulation, and the use of lysosomal-blocking compounds, distinguished CTLA-4 from LRBA mutations. Short-term T-cell stimulation improved the capacity for discriminating the Foxp3+ Treg compartment, clearly revealing Treg expansions in these disorders. Finally, we developed a functionally orientated assay to measure ligand uptake by CTLA-4, which is sensitive to ligand-binding or -trafficking mutations, that would otherwise be difficult to detect and that is appropriate for testing novel mutations in CTLA-4 pathway genes. These approaches are likely to be of value in interpreting the functional significance of mutations in the CTLA-4 pathway identified by gene-sequencing approaches.

We hypothesised that differences in cardiac baroreflex sensitivity (BRS) would be independently associated with aortic stiffness and augmentation index (AI), clinical biomarkers of cardiovascular disease risk, among young sedentary and middle-aged/older sedentary and endurance-trained adults. A total of 36 healthy middle-aged/older (age 55–76 years, n=22 sedentary and n=14 endurance-trained) and 5 young sedentary (age 18–31 years) adults were included in a cross-sectional study. A subset of the middle-aged/older sedentary adults (n=12) completed an 8-week-aerobic exercise intervention. Invasive brachial artery blood pressure waveforms were used to compute spontaneous cardiac BRS (via sequence technique), estimated aortic pulse wave velocity (PWV) and AI (AI, via brachial–aortic transfer function and wave separation analysis). In the cross-sectional study, cardiac BRS was 71% lower in older compared with young sedentary adults (P<0.05), but only 40% lower in older adults who performed habitual endurance exercise (P=0.03). In a regression model that included age, sex, resting heart rate, mean arterial pressure (MAP), body mass index and maximal exercise oxygen uptake, estimated aortic PWV (β±s.e.=−5.76±2.01, P=0.01) was the strongest predictor of BRS (model R2=0.59, P<0.001). The 8-week-exercise intervention improved BRS by 38% (P=0.04) and this change in BRS was associated with improved aortic PWV (r=−0.65, P=0.044, adjusted for changes in MAP). Age- and endurance-exercise-related differences in cardiac BRS are independently associated with corresponding alterations in aortic PWV among healthy adults, consistent with a mechanistic link between variations in the sensitivity of the baroreflex and aortic stiffness with age and exercise.

Recent advances in genetic engineering have enabled the delivery of clinical trials using patient T cells redirected to recognize tumor-associated antigens. The most dramatic results have been seen with T cells engineered to express a chimeric antigen receptor (CAR) specific for CD19, a differentiation antigen expressed in B cells and B lineage malignancies. We propose that antigen expression in nonmalignant cells may contribute to the efficacy of T-cell therapy by maintaining effector function and promoting memory. Although CAR recognition is limited to cell surface structures, T-cell receptors (TCRs) can recognize intracellular proteins. This not only expands the range of tumor-associated self-antigens that are amenable for T-cell therapy, but also allows TCR targeting of the cancer mutagenome. We will highlight biological bottlenecks that potentially limit mutation-specific T-cell therapy and may require high-avidity TCRs that are capable of activating effector function when the concentrations of mutant peptides are low. Unexpectedly, modified TCRs with artificially high affinities function poorly in response to low concentration of cognate peptide but pose an increased safety risk as they may respond optimally to cross-reactive peptides. Recent gene-editing tools, such as transcription activator–like effector nucleases and clustered regularly interspaced short palindromic repeats, provide a platform to delete endogenous TCR and HLA genes, which removes alloreactivity and decreases immunogenicity of third-party T cells. This represents an important step toward generic off-the-shelf T-cell products that may be used in the future for the treatment of large numbers of patients.

Recent advances in genetic engineering have enabled the delivery of clinical trials using patient T cells redirected to recognize tumor-associated antigens. The most dramatic results have been seen with T cells engineered to express a chimeric antigen receptor (CAR) specific for CD19, a differentiation antigen expressed in B cells and B lineage malignancies. We propose that antigen expression in nonmalignant cells may contribute to the efficacy of T-cell therapy by maintaining effector function and promoting memory. Although CAR recognition is limited to cell surface structures, T-cell receptors (TCRs) can recognize intracellular proteins. This not only expands the range of tumor-associated self-antigens that are amenable for T-cell therapy, but also allows TCR targeting of the cancer mutagenome. We will highlight biological bottlenecks that potentially limit mutation-specific T-cell therapy and may require high-avidity TCRs that are capable of activating effector function when the concentrations of mutant peptides are low. Unexpectedly, modified TCRs with artificially high affinities function poorly in response to low concentration of cognate peptide but pose an increased safety risk as they may respond optimally to cross-reactive peptides. Recent gene-editing tools, such as transcription activator–like effector nucleases and clustered regularly interspaced short palindromic repeats, provide a platform to delete endogenous TCR and HLA genes, which removes alloreactivity and decreases immunogenicity of third-party T cells. This represents an important step toward generic off-the-shelf T-cell products that may be used in the future for the treatment of large numbers of patients.

AbstractObjectiveWe aimed to quantitatively gauge local public health workers’ perceptions toward disaster recovery role expectations among jurisdictions in New Jersey and Maryland affected by Hurricane Sandy.MethodsAn online survey was made available in 2014 to all employees in 8 Maryland and New Jersey local health departments whose jurisdictions had been impacted by Hurricane Sandy in October 2012. The survey included perceptions of their actual disaster recovery involvement across 3 phases: days to weeks, weeks to months, and months to years. The survey also queried about their perceptions about future involvement and future available support.ResultsSixty-four percent of the 1047 potential staff responded to the survey (n=669). Across the 3 phases, 72% to 74% of the pre-Hurricane Sandy hires knew their roles in disaster recovery, 73% to 75% indicated confidence in their assigned roles (self-efficacy), and 58% to 63% indicated that their participation made a difference (response efficacy). Of the respondents who did not think it likely that they would be asked to participate in future disaster recovery efforts (n=70), 39% indicated a willingness to participate.ConclusionThe marked gaps identified in local public health workers’ awareness of, sense of efficacy toward, and willingness to participate in disaster recovery efforts after Hurricane Sandy represent a significant infrastructural concern of policy and programmatic relevance. (Disaster Med Public Health Preparedness. 2016;10:371–377)

The genetic engineering of T cells can lead to enhanced immune-mediated tumour destruction and harbors a great potential for the treatment of cancer. Recent efforts have centered on the design of receptors to re-direct the specificity of T cells towards tumour antigens by means of viral gene transfer. This strategy has shown great success in a number of phase one clinical trials. However, there are still challenges to overcome. On the one hand, T cell function can be further improved to optimize the therapeutic outcome. On the other hand, so called safety switches are required to deal with possible on and off target toxicities. In this review, we will give a brief summary of the success and risks of T cell gene therapy before discussing in detail current strategies to enhance effector function, persistence and safety of adoptively transferred T cells.

Maturation of high-affinity B lymphocytes is precisely controlled during the germinal center reaction. This is dependent on CD4+CXCR5+ follicular helper T cells (TFH) and inhibited by CD4+CXCR5+Foxp3+ follicular regulatory T cells (TFR). Because NFAT2 was found to be highly expressed and activated in follicular T cells, we addressed its function herein. Unexpectedly, ablation of NFAT2 in T cells caused an augmented GC reaction upon immunization. Consistently, however, TFR cells were clearly reduced in the follicular T cell population due to impaired homing to B cell follicles. This was TFR-intrinsic because only in these cells NFAT2 was essential to up-regulate CXCR5. The physiological relevance for humoral (auto-)immunity was corroborated by exacerbated lupuslike disease in the presence of NFAT2-deficient TFR cells.

Companies in the manufacturing industry today are faced with increasing challenges with respect to cost effectiveness, lead time and quality of the production system. Dealing with these contradictory goals, an important task is the selection of suitable solutions for the integration of inspection processes within the process chain, which are necessary to ensure the required production quality. For this, supportive and easily applicable planning techniques are required to analyze and design the configuration of a respective process chain. Value Stream Mapping (VSM) is a state of the art tool which is very often used for this by professionals. It, however, is not capable of addressing the issue of a suitable integration of testing processes within the process chain. Yet, this provides valuable potential to facilitate the identification of effective testing equipment, testing strategies and quality control loops. Therefore, in this article an innovative approach called Quality Value Stream Mapping (QVSM) is presented. Based on the design elements of VSM, it provides a suitable tool for the visualization, analysis and design of quality assurance measures within process chains in manufacturing. The implementation of the developed approach is exemplarily shown for a complex value chain of a manufacturer in the electronic industry.