Sustained Recruitment Research Articles

ZIC2 and ZIC3 promote SWI/SNF recruitment to safeguard progression towards human primed pluripotency

The primed epiblast acts as a transitional stage between the relatively homogeneous naïve epiblast and the gastrulating embryo. Its formation entails coordinated changes in regulatory circuits driven by transcription factors and epigenetic modifications. Using a multi-omic approach in human embryonic stem cell models across the spectrum of peri-implantation development, we demonstrate that the transcription factors ZIC2 and ZIC3 have overlapping but essential roles in opening primed-specific enhancers. Together, they are essential to facilitate progression to and maintain primed pluripotency. ZIC2/3 accomplish this by recruiting SWI/SNF to chromatin and loss of ZIC2/3 or degradation of SWI/SNF both prevent enhancer activation. Loss of ZIC2/3 also results in transcriptome changes consistent with perturbed Polycomb activity and a shift towards the expression of genes linked to differentiation towards the mesendoderm. Additionally, we find an intriguing dependency on the transcriptional machinery for sustained recruitment of ZIC2/3 over a subset of primed-hESC specific enhancers. Taken together, ZIC2 and ZIC3 regulate highly dynamic lineage-specific enhancers and collectively act as key regulators of human primed pluripotency.

Mathematical insights into the influence of delay and external recruitment on coral-macroalgae system

As anthropogenic pressures on coral reef ecosystems continue to increase due to global warming and mass coral bleaching events, there is growing interest in developing conservation strategies to restore degraded coral reefs. One such approach is the transplantation of coral larvae onto degraded reefs. In this paper, we use a delayed coral-macroalgae model to explore the effects of external recruitment of coral. By analyzing the local and global stability of macroalgae-free equilibrium and coexistence equilibrium in the system, we find that sustained external recruitment of coral will favor coral competition with macroalgae. In addition, we choose delay as a bifurcation parameter and demonstrate that Hopf bifurcation may occur at a critical delay near the coexistence equilibrium. Interestingly, the delay may cause the globally asymptotically stable equilibrium in the ODE system to become unstable, resulting in the appearance of periodic solutions. Furthermore, we analyze population dynamics using optimal control theory and determine the effect of minimum external recruitment on the population dynamics. In the numerical simulation section, parameters of coral-macroalgae dynamics are estimated by using a 12-year (2005–2017) benthic cover dataset of coral reefs in the Gulf of Mannar, southeastern India. The theoretical results are validated and supported by numerical simulations.

Engineered CD47 protects T cells for enhanced antitumour immunity

Adoptively transferred T cells and agents designed to block the CD47–SIRPα axis are promising cancer therapeutics that activate distinct arms of the immune system1,2. Here we administered anti-CD47 antibodies in combination with adoptively transferred T cells with the goal of enhancing antitumour efficacy but observed abrogated therapeutic benefit due to rapid macrophage-mediated clearance of T cells expressing chimeric antigen receptors (CARs) or engineered T cell receptors. Anti-CD47-antibody-mediated CAR T cell clearance was potent and rapid enough to serve as an effective safety switch. To overcome this challenge, we engineered the CD47 variant CD47(Q31P) (47E), which engages SIRPα and provides a ‘don’t eat me’ signal that is not blocked by anti-CD47 antibodies. TCR or CAR T cells expressing 47E are resistant to clearance by macrophages after treatment with anti-CD47 antibodies, and mediate substantial, sustained macrophage recruitment to the tumour microenvironment. Although many of the recruited macrophages manifested an M2-like profile3, the combined therapy synergistically enhanced antitumour efficacy. Our study identifies macrophages as major regulators of T cell persistence and illustrates the fundamental challenge of combining T-cell-directed therapeutics with those designed to activate macrophages. It delivers a therapeutic approach that is capable of simultaneously harnessing the antitumour effects of T cells and macrophages, offering enhanced potency against solid tumours.

Sustained vs. Intratidal Recruitment in the Injured Lung During Airway Pressure Release Ventilation: A Computational Modeling Perspective.

During mechanical ventilation, cyclic recruitment and derecruitment (R/D) of alveoli result in focal points of heterogeneous stress throughout the lung. In the acutely injured lung, the rates at which alveoli can be recruited or derecruited may also be altered, requiring longer times at higher pressure levels to be recruited during inspiration, but shorter times at lower pressure levels to minimize collapse during exhalation. In this study, we used a computational model to simulate the effects of airway pressure release ventilation (APRV) on acinar recruitment, with varying inspiratory pressure levels and durations of exhalation. The computational model consisted of a ventilator pressure source, a distensible breathing circuit, an endotracheal tube, and a porcine lung consisting of recruited and derecruited zones, as well as a transitional zone capable of intratidal R/D. Lung injury was simulated by modifying each acinus with an inflation-dependent surface tension. APRV was simulated for an inhalation duration (Thigh) of 4.0 seconds, inspiratory pressures (Phigh) of 28 and 40 cmH2O, and exhalation durations (Tlow) ranging from 0.2 to 1.5 seconds. Both sustained acinar recruitment and intratidal R/D within the subtree were consistently higher for Phigh of 40 cmH2O vs. 28 cmH2O, regardless of Tlow. Increasing Tlow was associated with decreasing sustained acinar recruitment, but increasing intratidal R/D, within the subtree. Increasing Tlow was associated with decreasing elastance of both the total respiratory system and transitional subtree of the model. Our computational model demonstrates the confounding effects of cyclic R/D, sustained recruitment, and parenchymal strain stiffening on estimates of total lung elastance during APRV. Increasing inspiratory pressures leads to not only more sustained recruitment of unstable acini but also more intratidal R/D. Our model indicates that higher inspiratory pressures should be used in conjunction with shorter exhalation times, to avoid increasing intratidal R/D.

“Whenever big changes come, big talks don't” – An examination of the police experience of recruitment and promotion positive action processes

Policing in England Wales is currently experiencing a large uplift in police recruitment. This has been due to the Government's target to uplift officers by 20,000. As a result, police forces are implementing large scale, sustained recruitment drives. These are accompanied by positive action schemes to address deficits in officer representation. Current statistics now indicate that representation in forces is rising slowly, as these initiatives are employed. There is little literature that examines the impact of positive action on existing police officers' perceptions, despite the initiative's relative proliferation. Procedural Justice theoretical literature is utilised to situate this in the research context.This study represents 17 theoretically informed, long form, phenomenological interviews conducted with serving officers in a uniform, response policing environment. The interviews were semi-structured, open ended and participant led, allowing the officers to present and explore their own thoughts and feelings about positive action, developed through their lived experience in an active police role. These interviews were conducted in an operational environment, from an insider-outsider perspective with total privacy. Officers openly discussed how they felt about the implementation of such policies and procedures.The findings indicate that a taboo exists with regards to the discussion of positive action processes in the police workplace. A juxtaposition also exists between the existence of positive action initiatives and the theme of meritocracy amongst the police officers. Officers strongly refuted the need for positive action to remedy issues with representation, but similarly criticised the current representation levels within forces. Theoretically this indicates an informational gap between police implementation of positive action interventions, and the perceived need for them to exist at all amongst rank and file. Implications for the study's findings are explored and possible remedies discussed.

Measuring service quality perceptions of hotel management institutes on hotel recruiters’ hiring intentions: effect of sacrifice, satisfaction and service value

ABSTRACT This study examined how service quality by institutes of hospitality management (IHM) in India affected hotel recruiters’ behavioral intentions of returning to campus for sustained recruitment activities. It further examined the underlying mechanisms of service value perceived by hotel recruiters, affected by the sacrifice made by hotel recruiters, as well as the satisfaction of hotel recruiters with IHM service quality and their behavioral intentions. A sample of 132 hotel recruiters from four international and domestic hotel organizations in India participated in a survey. Outcomes of structural equation modeling revealed that service quality, service value, and satisfaction were all predictors of behavioral intentions of the hotel recruiters. Sacrifice of hotel recruiters positively influenced their service value; service value perceived by hotel recruiters and their satisfaction were positively impacted by service quality; satisfaction and service value were the significant underlying mechanisms between service quality and behavioral intentions; and the relationship between service value and satisfaction was insignificant. These findings emphasize that IHMs improve performance by developing effective administrative policies and procedures that enhance the hiring intentions of hotel recruiters and in turn can elevate the reputation of the institutions with closely aligned academia-industry collaborations to achieve the sustainable development goals related to quality education.

Nonoptimal bacteria species induce neutrophil-driven inflammation and barrier disruption in the female genital tract

Neutrophil recruitment and activation within the female genital tract are often associated with tissue inflammation, loss of vaginal epithelial barrier integrity, and increased risk for sexually transmitted infections, such as HIV-1. However, the direct role of neutrophils on vaginal epithelial barrier function during genital inflammation in vivo remains unclear. Using complementary proteome and immunological analyses, we show high neutrophil influx into the lower female genital tract in response to physiological surges in progesterone, stimulating distinct stromal, immunological, and metabolic signaling pathways. However, despite the release of extracellular matrix-modifying proteases and inflammatory mediators, neutrophils contributed little to physiological mucosal remodeling events such as epithelial shedding or re-epithelialization during transition from diestrus to estrus phase. In contrast, the presence of bacterial vaginosis-associated bacteria resulted in a rapid and sustained neutrophil recruitment, resulting in vaginal epithelial barrier leakage and decreased cell-cell junction protein expression in vivo. Thus, neutrophils are important mucosal sentinels that rapidly respond to various biological cues within the female genital tract, dictating the magnitude and duration of the ensuing inflammatory response at steady state and during disease processes.

Tracking the Host Response to Infection in Peritoneal Models of Acute Resolving Inflammation.

Antimicrobial host defense is dependent on the rapid recruitment of inflammatory cells to the site of infection, the elimination of invading pathogens, and the efficient resolution of inflammation that minimizes damage to the host. The peritoneal cavity provides an accessible and physiologically relevant system where the delicate balance of these processes may be studied. Here, we describe murine models of peritoneal inflammation that enable studies of competent antimicrobial immunity and inflammation-associated tissue damage as a consequence of recurrent bacterial challenge. The inflammatory hallmarks of these models reflect the clinical and molecular features of peritonitis seen in renal failure patients on peritoneal dialysis. The development of these models relies on the preparation of a cell-free supernatant derived from an isolate of Staphylococcus epidermidis (termed SES). Intraperitoneal administration of SES induces a Toll-like receptor 2-driven acute inflammatory response that is characterized by an initial transient influx of neutrophils that are replaced by a more sustained recruitment of mononuclear cells and lymphocytes. Adaptation of this model using a repeated administration of SES allows investigations into the development of adaptive immunity and the hallmarks associated with tissue remodelling and fibrosis. These models are therefore clinically relevant and provide exciting opportunities to study innate and adaptive immunity and the response of the stromal tissue compartment to bacterial infection and the ensuing inflammatory reaction.

"You Can Change the World With a Haircut": Evaluating the Feasibility of a Barber-led Intervention for Men of Black and Ethnic Minority Heritage to Manage High Blood Pressure.

People of Black, Asian and minority ethnic (BAME) heritage have a higher-than-average incidence of, and mortality from hypertension and stroke. Therefore, it is important to identify new settings for engaging people at risk of high blood pressure (BP). This feasibility study aimed to evaluate if barbers in a London borough can support and educate men of BAME heritage to manage their BP. Following UK Medical Research Council guidance, the RE-AIM (reach, effectiveness, adoption, implementation, maintenance) framework was used to guide study objectives and feasibility outcomes. We collaborated with 8 barbers who were part of an existing BAME barber network. Barbers were trained online (1.5 h) and face-to-face (3 h) to provide BP healthcare advice and take customers BP readings. Qualitative field notes were collected to assess how best to recruit and train barbers, and to understand how to maintain motivation and retention of barbers. BP readings were recorded between June 2021 and March 2022. Both online and face-to-face training were effective, however, greater focus on how to start conversations about BP with clients was needed. We found that motivation, incentivization and regular contact with barbers were important for recruitment, retention, and sustained BP measurement. Obtaining BP readings was challenging due to client concerns about recording their data and the impracticalities of recording results. We captured 236 BP recordings, of which 39 (16.53%) were over 140/90 mmHg; of these, 5 were over 180/100 mmHg. The combined data showed that educating barbers to take BP readings and deliver healthcare advice about BP is a viable intervention for rollout in a large-scale study. It has demonstrated the need to identify strategies to motivate barbers for sustained recruitment and retention, as well as further efforts to build trust among customers for long-term BP surveillance.

Gonad development and recruitment pattern of the oysters Crassostrea ariakensis and Crassostrea sikamea in a subtropical bay in China

The extent of oyster stocks and their habitat loss experienced on the Chinese coasts suggests that oyster restoration will be necessary to rebuild direct fisheries and recover lost ecosystem services. Limited understanding of oyster biology and ecology is among the potential barriers to successful restoration along the Chinese coasts. At a natural oyster bed in Jiantiao Bay, Sanmen County, China, the study compared gonad development and spawn duration of the Sumonie oyster Crassostrea ariakensis and the Kumamoto oyster Crassostrea sikamea through histological sections from May 2020 to March 2021. Their temporal and vertical recruitment patterns were simultaneously observed along an increasing tidal elevation gradient (0.1 m, 0.6 m, 1.1 m, 1.6 m, 2.1 m). The gonad index did not differ between the oysters (P>0.05), with the maximum values in June–August, but C. sikamea had a longer spawning duration (May–December) than C. ariakensis (May–October). Crassostrea ariakensis recruited to only the lower 3 tidal zones (0.1 m, 0.6 m, 1.1 m), and its recruits varied linearly and significantly as an inverse function of tidal elevation. Significant 2nd degree polynomial fits best described the relationships for C. sikamea recruits and tidal elevation. The greatest recruits were commonly observed at the mid intertidal zones (0.6 m, 1.1 m and 1.6 m). An evident vertical settlement pattern emerged for C. sikamea at both 1-day and 3-day experiments; the greatest settlement rates occurred in the 1.6 m tidal zone, intermediate rates occurred in the 1.1 m and 0.6 m, the lowest rates occurred in the 0.1 m and 2.1 m. The study concluded that C. sikamea sustained longer spawning and recruitment durations than C. ariakensis, and a strong zonation pattern in recruitment emerged; C. sikamea achieved its maximum recruits in the mid-tidal zone, while the recruits of C. ariakensis linearly decreased with increasing tidal elevation.

H1N1 influenza virus dose dependent induction of dysregulated innate immune responses and STAT1/3 activation are associated with pulmonary immunopathological damage

ABSTRACT Influenza A virus (IAV) infection poses a substantial challenge and causes high morbidity and mortality. Exacerbated pulmonary inflammatory responses are the major causes of extensive diffuse alveolar immunopathological damage. However, the relationship between the extent of cytokine storm, neutrophils/macrophages infiltration, and different IAV infection dose and time still needs to be further elucidated, and it is still unclear whether the signal transduction and transcriptional activator 1/3 (STAT1/3) signalling pathway plays a beneficial or detrimental role. Here, we established a mouse model of high- and low-dose pH1N1 infection. We found that pH1N1 infection induced robust and early pathological damage and cytokine storm in an infection dose- and time-dependent manner. High-dose pH1N1 infection induced massive and sustained recruitment of neutrophils as well as a higher ratio of M1:M2, which may contribute to severe lung immunopathological damage. pH1N1 infection activated dose- and time-dependent STAT1 and STAT3. Inhibition of STAT1 and/or STAT3 aggravated low-dose pH1N1 infection, induced lung damage, and decreased survival rate. Appropriate activation of STAT1/3 provided survival benefits and pathological improvement during low-dose pH1N1 infection. These results demonstrate that high-dose pH1N1 infection induces robust and sustained neutrophil infiltration, imbalanced macrophage polarization, excessive and earlier cytokine storm, and STAT1/3 activation, which are associated with pulmonary dysregulated proinflammatory responses and progress of acute lung injury. The severe innate immune responses may be the threshold at which protective functions give way to immunopathology, and assessing the magnitude of host innate immune responses is necessary in adjunctive immunomodulatory therapy for alleviating influenza-induced pneumonia.

Effects of ultrasound-guided alveolar recruitment manoeuvres compared with sustained inflation or no recruitment manoeuvres on atelectasis in laparoscopic gynaecological surgery as assessed by ultrasonography: a randomized clinical trial

BackgroundThe majority of patients may experience atelectasis under general anesthesia, and the Trendelenburg position and pneumoperitoneum can aggravate atelectasis during laparoscopic surgery, which promotes postoperative pulmonary complications. Lung recruitment manoeuvres have been proven to reduce perioperative atelectasis, but it remains controversial which method is optimal. Ultrasonic imaging can be conducive to confirming the effect of lung recruitment manoeuvres. The purpose of our study was to assess the effects of ultrasound-guided alveolar recruitment manoeuvres by ultrasonography on reducing perioperative atelectasis and to check whether the effects of recruitment manoeuvres under ultrasound guidance (visual and semiquantitative) on atelectasis are superior to sustained inflation recruitment manoeuvres (classical and widely used) in laparoscopic gynaecological surgery.MethodsIn this randomized, controlled, double-blinded study, women undergoing laparoscopic gynecological surgery were enrolled. Patients were randomly assigned to receive either lung ultrasound-guided alveolar recruitment manoeuvres (UD group), sustained inflation alveolar recruitment manoeuvres (SI group), or no RMs (C group) using a computer-generated table of random numbers. Lung ultrasonography was performed at four predefined time points. The primary outcome was the difference in lung ultrasound score (LUS) among groups at the end of surgery.ResultsLung ultrasound scores in the UD group were significantly lower than those in both the SI group and the C group immediately after the end of surgery (7.67 ± 1.15 versus 9.70 ± 102, difference, -2.03 [95% confidence interval, -2.77 to -1.29], P < 0.001; 7.67 ± 1.15 versus 11.73 ± 1.96, difference, -4.07 [95% confidence interval, -4.81 to -3.33], P < 0.001;, respectively). The intergroup differences were sustained until 30 min after tracheal extubation (9.33 ± 0.96 versus 11.13 ± 0.97, difference, -1.80 [95% confidence interval, -2.42 to -1.18], P < 0.001; 9.33 ± 0.96 versus 10.77 ± 1.57, difference, -1.43 [95% confidence interval, -2.05 to -0.82], P < 0.001;, respectively). The SI group had a significantly lower LUS than the C group at the end of surgery (9.70 ± 1.02 versus 11.73 ± 1.96, difference, -2.03 [95% confidence interval, -2.77 to -1.29] P < 0.001), but the benefit did not persist 30 min after tracheal extubation.ConclusionsDuring general anesthesia, ultrasound-guided recruitment manoeuvres can reduce perioperative aeration loss and improve oxygenation. Furthermore, these effects of ultrasound-guided recruitment manoeuvres on atelectasis are superior to sustained inflation recruitment manoeuvres.Trial registrationChictr.org.cn, ChiCTR2100042731, Registered 27 January 2021, www.chictr.org.cn.

The C5a-C5aR1 complement axis is essential for neutrophil recruitment to draining lymph nodes via high endothelial venules in cutaneous leishmaniasis.

Neutrophils are specialized innate immune cells known for their ability to fight pathogens. However, the mechanisms of neutrophil trafficking to lymph nodes are not fully clear. Using a murine model of dermal infection with Leishmania parasites, we observe a transient neutrophil influx in draining lymph nodes despite sustained recruitment to the infection site. Cell-tracking experiments, together with intravital two-photon microscopy, indicate that neutrophil recruitment to draining lymph nodes occurs minimally through lymphatics from the infected dermis, but mostly through blood vessels via high endothelial venules. Mechanistically, neutrophils do not respond to IL-1β or macrophage-derived molecules. Instead, they are guided by the C5a-C5aR1 axis, using L-selectin and integrins, to extravasate into the draining lymph node parenchyma. We also report that C5, the C5a precursor, is locally produced in the draining lymph node by lymphatic endothelial cells. Our data establish and detail organ-specific mechanisms of neutrophil trafficking.

Reef design and site hydrodynamics mediate oyster restoration and marsh stabilization outcomes.

The detrimental ecological impacts of engineered shoreline protection methods (e.g., seawalls) and the need to protect the coastal zone have prompted calls for greater use of natural and nature-based infrastructure (NNBI). To balance competing needs of structural stability and ecological functioning, managers require assessments of NNBI designs and materials for differing environmental settings (e.g., among wave-energy regimes). To examine the effects of setting and oyster-based NNBI design on the provision of shoreline protection, we constructed reefs from two substrates: a novel, biodegradable material (Oyster Catcher, OC) and traditional oyster shell bags (SB) on low- and high-energy eroding salt marsh shorelines, designated based on fetch and boat wake exposure. Both reef types buffered marsh elevation change on the high-energy shoreline relative to unaltered controls, but only SB reefs were able to do so on the low-energy shoreline. Additionally, both shorelines experienced high ambient rates of retreat and declines in marsh vegetation shoot density. Although constructed reefs did not mitigate marsh retreat on the low-energy shoreline, novel OC reefs significantly reduced retreat relative to SB reefs and control sites (no reefs) on the high-energy shoreline. Those SB reefs were severely damaged by storm events, increasing their areal footprints at the expense of vertical relief. Conversely, OC reefs on both shorelines exhibited steady oyster recruitment and growth and hosted higher densities of larger oysters. To successfully provide shoreline stabilization benefits, oyster-based NNBI must be structurally stable and able to promote sustained oyster recruitment and growth. Our results indicate that deliberate decisions regarding NNBI substrate, siting, and configuration can produce resilient reefs, which reduce rates of erosion and, in some cases, enhance vertical accretion along salt marsh edges. The growth trajectory, structural stability, and co-benefit provisioning of OC reefs demonstrate the potential of alternative restoration substrates to provide valuable oyster habitat along threatened marsh shorelines.

Molecular Characterization and Functional Analysis of the Nattectin-like Toxin from the Venomous Fish Thalassophryne maculosa.

TmC4-47.2 is a toxin with myotoxic activity found in the venom of Thalassophryne maculosa, a venomous fish commonly found in Latin America whose envenomation produces an injury characterized by delayed neutrophil migration, production of major pro-inflammatory cytokines, and necrosis at the wound site, as well as a specific systemic immune response. However, there are few studies on the protein structure and functions associated with it. Here, the toxin was identified from the crude venom by chromatography and protein purification systems. TmC4-47.2 shows high homology with the Nattectin from Thalassophryne nattereri venom, with 6 cysteines and QPD domain for binding to galactose. We confirm its hemagglutinating and microbicide abilities independent of carbohydrate binding, supporting its classification as a nattectin-like lectin. After performing the characterization of TmC4-47.2, we verified its ability to induce an increase in the rolling and adherence of leukocytes in cremaster post-capillary venules dependent on the α5β1 integrin. Finally, we could observe the inflammatory activity of TmC4-47.2 through the production of IL-6 and eotaxin in the peritoneal cavity with sustained recruitment of eosinophils and neutrophils up to 24 h. Together, our study characterized a nattectin-like protein from T. maculosa, pointing to its role as a molecule involved in the carbohydrate-independent agglutination response and modulation of eosinophilic and neutrophilic inflammation.

Effects of an open lung ventilatory strategy on lung gas exchange during laparoscopic surgery.

In general anaesthesia, early collapse of poorly ventilated lung segments with low alveolar ventilation-perfusion ratios occurs and may lead to postoperative pulmonary complications after abdominal surgery. An 'open lung' ventilation strategy involves lung recruitment followed by 'individualised' positive end-expiratory pressure titrated to maintain recruitment of low alveolar ventilation-perfusion ratio lung segments. There are limited data in laparoscopic surgery on the effects of this on pulmonary gas exchange. Forty laparoscopic bowel surgery patients were randomly assigned to standard ventilation or an 'open lung' ventilation intervention, with end-tidal target sevoflurane of 1% supplemented by propofol infusion. After peritoneal insufflation, stepped lung recruitment was performed in the intervention group followed by maintenance positive end-expiratory pressure of 12-15 cmH2O adjusted to maintain dynamic lung compliance at post-recruitment levels. Baseline gas and blood samples were taken and repeated after a minimum of 30 minutes for oxygen and carbon dioxide and for sevoflurane partial pressures using headspace equilibration. The sevoflurane arterial/alveolar partial pressure ratio and alveolar deadspace fraction were unchanged from baseline and remained similar between groups (mean (standard deviation) control group = 0.754 (0.086) versus intervention group = 0.785 (0.099), P = 0.319), while the arterial oxygen partial pressure/fractional inspired oxygen concentration ratio was significantly higher in the intervention group at the second timepoint (control group median (interquartile range) 288 (234-372) versus 376 (297-470) mmHg in the intervention group, P = 0.011). There was no difference between groups in the sevoflurane consumption rate. The efficiency of sevoflurane uptake is not improved by open lung ventilation in laparoscopy, despite improved arterial oxygenation associated with effective and sustained recruitment of low alveolar ventilation-perfusion ratio lung segments.

Peeling the paradigm: Exploring the professionalization of policing in Canada

Maintaining public trust, legitimacy, and credibility in a constantly evolving society has proven challenging for police in the 21st century. Rising public concerns regarding police accountability are driving the need to advance the paradigm of policing by reassessing the organizational structure of law enforcement in Canada. Supported by research identifying primary directives for maintaining public trust, this proposal argues that the time has come for policing to evolve from an occupation into a formal profession. Just as any other occupation that has advanced into a profession, provincial regulatory colleges of policing should be formed with the key objective of protecting the public from malpractice and malfeasance. A provincial college of policing would allow for (a) sustained and inclusive recruitment strategies, (b) foundational knowledge of the scholarship of policing, (c) evidence-based academy training, (d) mandatory ongoing (in-service) police education, and (e) expert, objective, community-focused, independent oversight. This proposal uses characteristics of the College of Policing in England and Wales as a guiding framework for the support and preparation of professionalizing policing in Canada.

Angiotensin II Type 1 Receptor Tachyphylaxis Is Defined by Agonist Residence Time.

Several GPCRs (G-protein-coupled receptors) have been reported to exhibit tachyphylaxis, which is an acute loss of functional receptor response after repeated stimuli with an agonist. GPCRs are important clinical targets for a wide range of disorders. Therefore, elucidation of the ligand features that contribute to receptor tachyphylaxis and signaling events underlying this phenomenon is important for drug discovery and development. In this study, we examined the role of ligand-binding kinetics in the tachyphylaxis of AT1R (angiotensin II type 1 receptor) using bioluminescence resonance energy transfer assays to monitor signaling events under both kinetic and equilibrium conditions. We investigated AT1R signal transduction and translocation promoted by the endogenous tachyphylactic agonist Ang II (angiotensin II) and its analogs, described previously for inducing reduced receptor tachyphylaxis. Estimation of binding kinetic parameters of the ligands revealed that the residence time of Ang II was higher than that of the analogs, resulting in more sustained Gq protein activation and recruitment of β-arrestin than that promoted by the analogs. Furthermore, we observed that Ang II led to more sustained internalization of the receptor, thereby retarding its recycling to the plasma membrane and preventing further receptor responses. These results show that the apparent lack of tachyphylaxis in the studied analogs resulted from their short residence time at the AT1R. In addition, our data highlight the relevance of complete characterization of novel GPCR drug candidates, taking into account their receptor binding kinetics as well.

Recruitment Bottlenecks for Age‐0 Walleye in Northern Wisconsin Lakes

AbstractSome northern Wisconsin lakes have shown declines in catches of age‐0 Walleye Sander vitreus in standardized fall electrofishing sampling, suggesting that recruitment bottlenecks are occurring in the first several months of life. In 2016 and 2017, we sampled six lakes with declining trends in natural Walleye recruitment (D‐NR lakes) and seven lakes with a history of sustained natural recruitment (S‐NR lakes) to determine if timing of potential recruitment bottlenecks for age‐0 Walleye were consistent among D‐NR lakes and if abiotic and biotic metrics differed between D‐NR and S‐NR lakes. We also examined diets of larval Walleye to assess prey items that may be important to early growth and survival and to determine if occurrence of piscivory was related to larval Walleye total length. Differential patterns in the presence and absence of age‐0 Walleye at different life history stages in the first 6 months of life suggested that recruitment bottlenecks in D‐NR lakes were consistently occurring before mid‐July (five of six lakes). Mean Secchi depth, surface conductivity, abundance of larval Yellow Perch Perca flavescens, and most metrics of zooplankton abundance and mean size were similar between D‐NR and S‐NR lakes. Log10 transformed number of adult Walleye per hectare was lower and adult mean total length was higher in D‐NR lakes. Across all lakes, diets of larval Walleye consisted of zooplankton and larval fish and the occurrence of piscivory was higher than reported in previous studies and was positively related to total length of larval Walleye. Causes of recruitment bottlenecks in D‐NR lakes remain unclear, making it difficult to identify management actions that might be implemented to circumvent these bottlenecks. However, our results indicate that future research should focus on the period between egg deposition and mid‐July.

Gender and racial disparities in the transplant surgery workforce.

This review explores trends in the United States (US) transplant surgery workforce with a focus on historical demographics, post-fellowship job market, and quality of life reported by transplant surgeons. Ongoing efforts to improve women and racial/ethnic minority representation in transplant surgery are highlighted. Future directions to create a transplant workforce that reflects the diversity of the US population are discussed. Representation of women and racial and ethnic minorities among transplant surgeons is minimal. Although recent data shows an improvement in the number of Black transplant surgeons from 2% to 5.5% and an increase in women to 12%, the White to Non-White transplant workforce ratio has increased 35% from 2000 to 2013. Transplant surgeons report an average of 4.3 call nights per week and less than five leisure days a month. Transplant ranks 1st among surgical sub-specialties in the prevalence of three well-studied facets of burnout. Concerns about lifestyle may contribute to the decreasing demand for advanced training in abdominal transplantation by US graduates. Minimal improvements have been made in transplant surgery workforce diversity. Sustained and intentional recruitment and promotion efforts are needed to improve the representation of women and minority physicians and advanced practice providers in the field.