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Natural killer (NK) cells are potent innate immune system effector lymphocytes armed with multiple mechanisms for killing cancer cells. Given the dynamic roles of NK cells in tumor surveillance, they are fast becoming a next-generation tool for adoptive immunotherapy. Many strategies are being employed to increase their number and improve their ability to overcome cancer resistance and the immunosuppressive tumor microenvironment. These include the use of cytokines and synthetic compounds to bolster propagation and killing capacity, targeting immune-function checkpoints, addition of chimeric antigen receptors (CARs) to provide cancer specificity and genetic ablation of inhibitory molecules. The next generation of NK cell products will ideally be readily available as an “off-the-shelf” product and stem cell derived to enable potentially unlimited supply. However, several considerations regarding NK cell source, genetic modification and scale up first need addressing. Understanding NK cell biology and interaction within specific tumor contexts will help identify necessary NK cell modifications and relevant choice of NK cell source. Further enhancement of manufacturing processes will allow for off-the-shelf NK cell immunotherapies to become key components of multifaceted therapeutic strategies for cancer.

Hearing is essential for the courtship of one of the major carriers of human disease, the mosquito. Males locate females through flight-tone recognition and both sexes engage in mid-air acoustic communications, which can take place within swarms containing thousands of individuals. Despite the importance of hearing for mosquitoes, its mechanisms are still largely unclear. We here report a multilevel analysis of auditory function across three disease-transmitting mosquitoes ( Aedes aegypti , Anopheles gambiae and Culex quinquefasciatus ). All ears tested display transduction-dependent power gain. Quantitative analyses of mechanotransducer function reveal sex-specific and species-specific variations, including male-specific, highly sensitive transducer populations. Systemic blocks of neurotransmission result in large-amplitude oscillations only in male flagellar receivers, indicating sexually dimorphic auditory gain control mechanisms. Our findings identify modifications of auditory function as a key feature in mosquito evolution. We propose that intra-swarm communication has been a driving force behind the observed sex-specific and species-specific diversity. Auditory processing is an important component of mosquito behaviour including mating. Here the authors demonstrate substantial sex- and also species-specific variation in mosquito auditory transduction, amplification and gain control.

The alpha-particle X-ray spectrometer (APXS) for the Mars Science Laboratory (MSL) mission was calibrated for routine analysis of: Na, Mg, Al, Si, P, S, Cl, K, Ca, Ti, Cr, Mn, Fe, Ni, Zn, Br, Rb, Sr, and Y. The following elements were also calibrated, but may be too low to be measured (10s–100s ppm) for their usual abundance on Mars: V, Cu, Ga, As, Se and W. An extensive suite of geological reference materials, supplemented by pure chemical elements and compounds was used. Special attention was paid to include phyllosilicates, sulfates and a broad selection of basalts as these are predicted minerals and rocks at the Gale Crater landing site. The calibration approach is from first principles, using fundamental physics parameters and an assumed homogeneous sample matrix to calculate expected elemental signals for a given instrument setup and sample composition. Resulting concentrations for most elements accord with expected values. Deviations in elements of lower atomic number (Na, Mg, Al) indicate significant influences of mineral phases, especially in basalts, ultramafic rocks and trachytes. The systematics of these deviations help us to derive empirical, iterative corrections for different rock groups, based on a preliminary APXS analysis which assumes a homogeneous sample. These corrections have the potential to significantly improve the accuracy of APXS analyses, especially when other MSL instrument results, such as the X-ray diffraction data from CheMin, are included in the overall analysis process.

Cellular immunotherapy is revolutionizing cancer treatment. However, autologous transplants are complex, costly, and limited by the number and quality of T cells that can be isolated from and expanded for re-infusion into each patient. This paper demonstrates a stromal support cell-free in vitro method for the differentiation of T cells from umbilical cord blood hematopoietic stem cells (HSCs). For each single HSC cell input, approximately 5 × 104 T cells were created with an initial five days of HSC expansion and subsequent T cell differentiation over 49 days. When the induced in vitro differentiated T cells were activated by cytokines and anti-CD3/CD28 beads, CD8+ T cell receptor (TCR) γδ+ T cells were preferentially generated and elicited cytotoxic function against ovarian cancer cells in vitro. This process of inducing de novo functional T cells offers a possible strategy to increase T cell yields, simplify manufacturing, and reduce costs with application potential for conversion into chimeric antigen receptor (CAR)-T cells for cancer immunotherapy and for allogeneic transplantation to restore immune competence.

Background Safe surgery requires high-quality, reliable lighting of the surgical field. Little is reported on the quality or potential safety impact of surgical lighting in low-resource settings, where power failures are common and equipment and resources are limited. Methods Members of the Lifebox Foundation created a novel, non-mandatory, 18-item survey tool using an iterative process. This was distributed to surgical providers practicing in low-resource settings through surgical societies and mailing lists. Results We received 100 complete responses, representing a range of surgical centres from 39 countries. Poor-quality surgical field lighting was reported by 40% of respondents, with 32% reporting delayed or cancelled operations due to poor lighting and 48% reporting electrical power failures at least once per week. Eighty per cent reported the quality of their surgical lighting presents a patient safety risk with 18% having direct experience of poor-quality lighting leading to negative patient outcomes. When power outages occur, 58% of surgeons rely on a backup generator and 29% operate by mobile phone light. Only 9% of respondents regularly use a surgical headlight, with the most common barriers reported as unaffordability and poor in-country suppliers. Conclusions In our survey of surgeons working in low-resource settings, a majority report poor surgical lighting as a major risk to patient safety and nearly one-third report delayed or cancelled operations due to poor lighting. Developing and distributing robust, affordable, high-quality surgical headlights could provide an ideal solution to this significant surgical safety issue.

Natural killer (NK) cell immunotherapies for cancer can complement existing T cell therapies while benefiting from advancements already made in the immunotherapy field. For NK cell manufacturing, induced pluripotent stem cells (iPSCs) offer advantages including eliminating donor variation and providing an ideal platform for genome engineering. At the same time, extracellular vesicles (EVs) have become a major research interest, and purified NK cell extracellular vesicles (NKEVs) have been shown to reproduce the key functions of their parent NK cells. NKEVs have the potential to be developed into a standalone therapeutic with reduced complexity and immunogenicity compared to cell therapies. This review explores the role iPSC technology can play in both NK cell manufacturing and NKEV development.

The present study investigates the role of psychological resilience in protecting against the development of post-traumatic stress disorder (PTSD), depression, and comorbid PTSD and depression; and estimates the percent reductions in incidence of, and associated treatment cost savings for, each condition as a function of increasing resilience. A retrospective cohort of mental health care-seeking service members (n = 2,171) completed patient-reported outcome measures approximately every 10 weeks as part of the Psychological Health Pathways program. Patients with low resilience were at significantly greater odds for developing physical, behavioral, and mental health conditions, particularly sleep disorder (adjusted odds ratio [AOR] = 2.60, 95% confidence interval [CI] = 1.81-3.73), perceived stress (AOR = 2.86, 95% CI = 1.05-7.75), and depression (AOR = 2.89, 95% CI = 2.34-3.57) compared to patients with moderate/high resilience. Increasing resilience across services by 20% is estimated to reduce the odds of developing PTSD, depression, and comorbid PTSD and depression by 73%, 54%, and 93%, respectively; the incidence by 32%, 19%, and 61%, respectively; and save approximately $196, $288, and $597 million in annual treatment costs, respectively, or approximately $1.1 billion total (a 35% reduction in costs). Using resilience as a preventive model may reduce health care utilization and costs in an already overtaxed health care system.

ObjectiveElastomeric devices or pumps are a valuable tool to deliver outpatient parenteral therapy and have been used for administration of chemotherapy, antibiotics and pain medication. A key determinant of effective treatment is to consider the stability of medicines within these devices. It is widely known that an increase in temperature positively correlates to an increase in drug degradation. The objective of our work was to measure the temperature within soft shell elastomeric devices, under simulated outpatient treatment conditions in summer and winter months, and to determine the maximum temperature reached within these periods of use.MethodsThermocouples were inserted within soft shell Easypump II (B Braun Medical, Sheffield, UK) elastomeric pumps and the temperature was monitored under simulated outpatient conditions during cold and warm weather with different fill volumes. Temperature monitoring was also conducted with varying levels of insulation around the devices.ResultsOur results show that internal temperatures remained below 32°C±1°C in winter and summer months, including during times defined as a heatwave. Fill volume and ambient temperature were shown to be significant factors affecting the internal temperatures reached.ConclusionA soft shell Easypump II elastomeric pump, if used within its carry pouch, will maintain the internal solution below a temperature of 32°C±1°C if patients correctly adhere to handling guidance. Our results show that further improvements to the insulation material used in carry pouches can significantly restrict the rate of temperature rise within the pumps and will give more assurance in relation to preventing degradation especially considering the increases in extreme weather conditions observed in recent years due to global warming.

ObjectiveTo gain an understanding of what challenges pulse oximetry for paediatric pneumonia management poses, how it has changed service provision and what would improve this device for use across paediatric clinical settings in low-income countries.DesignFocus group discussions (FGDs), with purposive sampling and thematic analysis using a framework approach.SettingCommunity, front-line outpatient, and hospital outpatient and inpatient settings in Malawi and Bangladesh, which provide paediatric pneumonia care.ParticipantsHealthcare providers (HCPs) from Malawi and Bangladesh who had received training in pulse oximetry and had been using oximeters in routine paediatric care, including community healthcare workers, non-physician clinicians or medical assistants, and hospital-based nurses and doctors.ResultsWe conducted six FGDs, with 23 participants from Bangladesh and 26 from Malawi. We identified five emergent themes: trust, value, user-related experience, sustainability and design. HCPs discussed the confidence gained through the use of oximeters, resulting in improved trust from caregivers and valuing the device, although there were conflicts between the weight given to clinical judgement versus oximeter results. HCPs reported the ease of using oximeters, but identified movement and physically smaller children as measurement challenges. Challenges in sustainability related to battery durability and replacement parts, however many HCPs had used the same device longer than 4 years, demonstrating robustness within these settings. Desirable features included back-up power banks and integrated respiratory rate and thermometer capability.ConclusionsPulse oximetry was generally deemed valuable by HCPs for use as a spot-check device in a range of paediatric low-income clinical settings. Areas highlighted as challenges by HCPs, and therefore opportunities for redesign, included battery charging and durability, probe fit and sensitivity in paediatric populations.Trial registration numberNCT02941237.