Resilience and fragmentation in healthcare coalitions: The link between resource contributions and centrality in health-related interorganizational networks.

Interorganizational coalitions or collaboratives in healthcare are essential to address the health challenges of local communities, particularly during crises such as the Covid-19 pandemic. However, few studies use large-scale data to systematically assess the network structure of these collaboratives and understand their potential to be resilient or fragment in the face of structural changes. This paper analyzes data collected in 2009-2017 about 817 organizations (nodes) in 42 healthcare collaboratives (networks) throughout Florida, the third-largest U.S. state by population, including information about interorganizational ties and organizations' resource contributions to their coalitions. Social network methods are used to characterize the resilience of these collaboratives, including identification of key players through various centrality metrics, analyses of fragmentation centrality and core/periphery structure, and Exponential Random Graph Models to examine how resource contributions facilitate interorganizational ties. Results show that the most significant resource contributions are made by key players identified through fragmentation centrality and by members of the network core. Departure or removal of these organizations would both strongly disrupt network structure and sever essential resource contributions, undermining the overall resilience of a collaborative. Furthermore, one-third of collaboratives are highly susceptible to disruption if any fragmentation-central organization is removed. More fragmented networks are also associated with poorer health-system outcomes in domains such as education, health policy, and services. ERGMs reveal that two types of resource contributions - community connections and in-kind resource sharing - are especially important to facilitate the formation of interorganizational ties in these coalitions.

Radiomic Signatures Associated with CD8+ Tumour-Infiltrating Lymphocytes: A Systematic Review and Quality Assessment Study.

The tumour immune microenvironment influences the efficacy of immune checkpoint inhibitors. Within this microenvironment are CD8-expressing tumour-infiltrating lymphocytes (CD8+ TILs), which are an important mediator and marker of anti-tumour response. In practice, the assessment of CD8+ TILs via tissue sampling involves logistical challenges. Radiomics, the high-throughput extraction of features from medical images, may offer a novel and non-invasive alternative. We performed a systematic review of the available literature reporting radiomic signatures associated with CD8+ TILs. We also aimed to evaluate the methodological quality of the identified studies using the Radiomics Quality Score (RQS) tool, and the risk of bias and applicability with the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Articles were searched from inception until 31 December 2021, in three electronic databases, and screened against eligibility criteria. Twenty-seven articles were included. A wide variety of cancers have been studied. The reported radiomic signatures were heterogeneous, with very limited reproducibility between studies of the same cancer group. The overall quality of studies was found to be less than desirable (mean RQS = 33.3%), indicating a need for technical maturation. Some potential avenues for further investigation are also discussed.

Alteration of the expression of sirtuins and var genes by heat shock in the malaria parasite Plasmodium falciparum.

BACKGROUND: In Plasmodium falciparum the monoallelic expression of var virulence genes is regulated through epigenetic mechanisms. A study in the Gambia showed that an increase in var genes commonly expressed in patients with severe malaria is associated with fever and high blood lactate. A strong association was demonstrated between the upregulation of PfSir2A and group B var genes. A subsequent study in Kenya extended this association to show a link between elevated expression of PfSir2A and overall var transcript levels. We investigate here the link between heat shock and/or lactate levels on sirtuin and var gene expression levels in vitro. METHODS: In vitro experiments were conducted using laboratory and recently-laboratory-adapted Kenyan isolates of P. falciparum. To investigate a potential cause-and-effect relationship between host stress factors and parasite gene expression, qPCR was used to measure the expression of sirtuins and var genes after highly synchronous cultured parasites had been exposed to 2 h or 6 h of heat shock at 40 °C or elevated lactate. RESULTS: Heat shock was shown to increase the expression ofPfSir2B in the trophozoites, whereas exposure to lactate was not. After the ring stages were exposed to heat shock and lactate, there was no alteration in the expression of sirtuins and severe-disease-associated upsA and upsB var genes. The association between high blood lactate and sirtuin/var gene expression that was previously observed in vivo appears to be coincidental rather than causative. CONCLUSIONS: This study demonstrates that heat stress in a laboratory and recently-laboratory-adapted isolates of P. falciparum results in a small increase in PfSir2B transcripts in the trophozoite stages only. This finding adds to our understanding of how patient factors can influence the outcome of Plasmodium falciparum infections.

Effect of ß-1/3,1/6-glucan upon immune responses and bacteria in the gut of healthy common carp (Cyprinus carpio).

ß-glucans are frequently included in the diet of healthy common carp Cyprinus carpio as a pre-emptive measure for combatting disease. In order to study the effect this has on the relationship between the gut bacteria and host immune response, carp were maintained on either a ß-glucan free diet or feed containing 0.1% MacroGard®, a ß-1/3, 1/6-glucan, for up to 7 weeks and analysis of innate immune gene expression and molecular analysis of the gut bacteria was performed. The data reveals feeding of MacroGard® to healthy carp does not induce bactericidal innate immune gene expression in the gut but does appear to alter bacterial species richness that did not have a negative effect on overall health. Analysis of innate immune gene expression within the upper midgut revealed that there were significant changes over time in the expression of Interleukin (il)-1ß, inducible nitric oxide synthase (inos), mucin (muc2) and C-reactive protein (crp2). Diet did not affect the number of copies of the bacterial 16s rDNA gene in the gut, used as a as a measure of total bacteria population size. However, PCR-denaturing gradient gel electrophoresis (DGGE) analysis revealed a shift in bacterial species richness with MacroGard feeding. Bactericidal immune gene expression of crp2, muc2 and il-1ß was weakly correlated with gut bacteria population size indicating a potentially limited role of these genes in interacting with the gut bacteria in healthy carp in order to maintain gut homeostatic conditions. These findings highlight the importance of considering both host immunity and the microbiome together in order to fully elucidate the effeect of immunomodulants, such as ß-glucans, upon gut health.

Plantar pressure differences between cases with symptoms of clinically diagnosed chronic exertional compartment syndrome and asymptomatic controls.

BACKGROUND: Anterior chronic exertional compartment syndrome of the leg has been hypothesised to develop due to excessive muscle activity and foot pronation. Plantar pressure variables related to lower limb muscle activity and foot type may therefore provide insight into this condition. METHODS: 70 male cases and 70 asymptomatic controls participated. A clinical diagnosis was established from typical symptoms, with clinical examination excluding other pathologies. Plantar pressure variables during walking, hypothesised to be related to foot type, toe extensor activity or had shown predictive validity for general exercise-related lower leg pain, were extracted. FINDINGS: Cases were shorter in height (mean difference 2.4cm), had greater body mass (mean difference 4.4kg) and had reduced ankle dorsiflexion range of motion than controls (mean difference 1.5cm). Plantar pressure variables indicative of foot-type and toe extensor activity did not differ between groups (P>0.05). The magnitude of medial forefoot loading was the strongest plantar pressure predictor of the presence of chronic exertional compartment syndrome (Odds ratio:0.87, P=0.005). There was also some evidence of greater lateral heel loading at 5% of stance time (P=0.049-0.054). INTERPRETATION: The lack of association with foottype-related and toe extensor activity-related plantar pressure variables suggest that these are not risk factors for the development of chronic exertional compartment syndrome, contrary to earlier hypotheses. The greater lateral to medial loading could theoretically represent increased Tibialis anterior muscle activity at heel strike but a subsequent loss of control as the ankle is lowered. Future studies directly investigating muscle activity and function are now required.

Biomechanical differences between cases with suspected chronic exertional compartment syndrome and asymptomatic controls during running.

Chronic exertional compartment syndrome (CECS) has been hypothesised, following clinical observations, to be the result of abnormal biomechanics predominantly at the ankle. Treatment of CECS through running re-education to correct these abnormalities has been reported to improve symptoms. However no primary research has been carried out to investigate the movement patterns of those with CECS. This study aimed to compare the running kinematics and muscle activity of cases with CECS and asymptomatic controls. 20 men with bilateral symptoms of CECS of the anterior compartment and 20 asymptomatic controls participated. Barefoot and shod running 3D kinematics and muscle activity of the left and right legs; and anthropometry were compared. Cases displayed less anterior trunk lean and less anterior pelvic tilt throughout the whole gait cycle and a more upright shank inclination angle during late swing (peak mean difference 3.5°, 4.1° and 7.3° respectively). Cases demonstrated greater step length and stance time, although this was not consistent across analyses. There were no consistent differences in Tibialis anterior or Gastrocnemius medialis muscle activity. Cases were heavier (mean difference 7.9kg, p=0.02) than controls with no differences in height (p>0.05) These differences only partially match the clinical observations previously described. However, no consistent differences were found at the ankle joint suggesting that current running re-education interventions which focus on adjusting ankle kinematics are not modifying pathological aspects of gait. The longer step length is a continuing theme in this population and as such may be a key component in the development of CECS.

Biomechanical differences between cases with chronic exertional compartment syndrome and asymptomatic controls during walking and marching gait.

Chronic exertional compartment syndrome is a significant problem in military populations that may be caused by specific military activities. This study aimed to investigate the kinematic and kinetic differences in military cases with chronic exertional compartment syndrome and asymptomatic controls. 20 males with symptoms of chronic exertional compartment syndrome of the anterior compartment and 20 asymptomatic controls were studied. Three-dimensional lower limb kinematics and kinetics were compared during walking and marching. Cases were significantly shorter in stature and took a relatively longer stride in relation to leg length than controls. All kinematic differences identified were at the ankle. Cases demonstrated increased ankle plantarflexion from mid-stance to toe-off. Cases also demonstrated less ankle inversion at the end of stance and early swing phases. Lower ankle inversion moments were observed during mid-stance. The anthropometric and biomechanical differences demonstrated provide a plausible mechanism for the development of chronic exertional compartment syndrome in this population. The shorter stature in combination with the relatively longer stride length observed in cases may result in an increased demand on the anterior compartment musculature during ambulation. The results of this study, together with clinical insights and the literature suggest that the suppression of the walk-to-run stimulus during group marches may play a significant role in the development of chronic exertional compartment syndrome within a military population. The differences in joint angles and moments also suggest an impairment of the muscular control of ankle joint function, such as a reduced effectiveness of tibialis anterior. It is unclear whether this is a cause or consequence of chronic exertional compartment syndrome.

Intramuscular compartment pressure measurement in chronic exertional compartment syndrome: new and improved diagnostic criteria.

BACKGROUND: Patients with chronic exertional compartment syndrome (CECS) have pain during exercise that subsides with rest. Diagnosis is usually confirmed by intramuscular compartment pressure (IMCP) measurement. Controversy exists regarding the accuracy of existing diagnostic criteria. PURPOSE: (1) To compare dynamic IMCP measurement and anthropometric factors between patients with CECS and asymptomatic controls and (2) to establish the diagnostic utility of dynamic IMCP measurement. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 2. METHODS: A total of 40 men aged 21 to 40 years were included in the study: 20 with symptoms of CECS of the anterior compartment and 20 asymptomatic controls. Diagnoses other than CECS were excluded with rigorous inclusion criteria and magnetic resonance imaging. The IMCP was measured continuously before, during, and after participants exercised on a treadmill, wearing identical footwear and carrying a 15-kg load. RESULTS: Pain experienced by study subjects increased incrementally as the study progressed (P < .001). Pain levels experienced by the case group during each phase of the exercise were significantly different (P = .021). Subjects had higher IMCP immediately upon standing at rest compared with controls (23.8 mm Hg [controls] vs 35.5 mm Hg [subjects]; P = .006). This relationship persisted throughout the exercise protocol, with the greatest difference corresponding to the period of maximal tolerable pain (68.7 mm Hg [controls] vs 114 mm Hg [subjects]; P < .001). Sensitivity and specificity were consistently higher than the existing criteria with improved diagnostic value (sensitivity = 63%, specificity = 95%; likelihood ratio = 12.5 [95% CI, 3.2-49]). CONCLUSION: Anterior compartment IMCP is elevated immediately upon standing at rest in subjects with CECS. In patients with symptoms consistent with CECS, diagnostic utility of IMCP measurement is improved when measured continuously during exercise. A cutoff of 105 mm Hg in phase 2 provides better diagnostic accuracy than do the Pedowitz criteria of 30 mm Hg and 20 mm Hg at 1 and 5 minutes after exercise, respectively.

Shoulder instability in professional rugby players-the significance of shoulder laxity.

OBJECTIVE: Shoulder instability is a common cause of morbidity among professional rugby union players. This study explores whether the risk of shoulder dislocation is associated with innate shoulder laxity. DESIGN: Retrospective cohort study. SETTING: Clinical sports medicine research at professional rugby clubs. PARTICIPANTS: One hundred sixty-nine healthy rugby players (mean age 25.1 years) with no history of instability in either shoulder and 46 players (mean age 27.5 years) with shoulder instability in one shoulder (patient group). MAIN OUTCOME MEASURES: Anterior, inferior, and posterior laxity was measured in both shoulders for healthy players and in the uninjured shoulder only for injured players using dynamic ultrasound. RESULTS: There was no significant difference between the nondominant (anterior: mean 2.9 ± 1.2 mm; inferior: mean 3.1 ± 1.0 mm; posterior: mean 5.1 ± 1.7 mm) and dominant (anterior: mean 3.1 ± 1.1 mm; inferior: mean 2.9 ± 1.0 mm; posterior: mean 4.9 ± 1.7 mm) shoulders in healthy players (P > 0.05). The comparison between healthy shoulders (anterior: mean 3.0 ± 1.2 mm; inferior: mean 3.0 ± 1.0 mm; posterior: mean 5.0 ± 1.7 mm) and the uninjured shoulder (anterior: mean 4.2 ± 1.7 mm; inferior: mean 3.4 ± 1.2 mm; posterior: mean 6.2 ± 3.0 mm) from injured players identified that players with unstable shoulders have a significantly higher shoulder translation in their uninjured shoulder than healthy players (P < 0.05). CONCLUSIONS: Formal assessment of shoulder translation using dynamic ultrasound should enable sports medicine practitioners to identify players at greatest risk of subsequent shoulder instability for targeted prehabilitation programs.

Enhancing the engagement of U.S. private foundations with conservation science.

Funding for conservation is limited, and its investment for maximum conservation gain can likely be enhanced through the application of relevant science. Many donor institutions support and use science to pursue conservation goals, but their activities remain relatively unfamiliar to the conservation-science community. We examined the priorities and practices of U.S.-based private foundations that support biodiversity conservation. We surveyed 50 donor members of the Consultative Group on Biological Diversity (CGBD) to address three questions: (1) What support do CGBD members provide for conservation science? (2) How do CGBD members use conservation science in their grant making and strategic thinking? (3) How do CGBD members obtain information about conservation science? The 38 donor institutions that responded to the survey made $340 million in grants for conservation in 2005, including $62 million for conservation science. Individual foundations varied substantially in the proportion of conservation funds allocated to science. Foundations also varied in the ways and degree to which they used conservation science to guide their grant making. Respondents found it "somewhat difficult" to stay informed about conservation science relevant to their work, reporting that they accessed conservation science information mainly through their grantees. Many funders reported concerns about the strategic utility of funding conservation science to achieve conservation gains. To increase investment by private foundations in conservation science, funders, researchers, and conservation practitioners need to jointly identify when and how new scientific knowledge will lower barriers to conservation gains. We envision an evolving relationship between funders and conservation scientists that emphasizes primary research and synthesis motivated by (1) applicability, (2) human-ecosystem interactions, (3) active engagement among scientists and decision makers, and (4) broader communication of relevant scientific information.