Global taxonomic, functional, and phylogenetic diversity of bees in apple orchards.

An essential prerequisite to safeguard pollinator species is characterisation of the multifaceted diversity of crop pollinators and identification of the drivers of pollinator community changes across biogeographical gradients. The extent to which intensive agriculture is associated with the homogenisation of biological communities at large spatial scales remains poorly understood. In this study, we investigated diversity drivers for 644 bee species/morphospecies in 177 commercial apple orchards across 33 countries and four global biogeographical biomes. Our findings reveal significant taxonomic dissimilarity among biogeographical zones. Interestingly, despite this dissimilarity, species from different zones share similar higher-level phylogenetic groups and similar ecological and behavioural traits (i.e. functional traits), likely due to habitat filtering caused by perennial monoculture systems managed intensively for crop production. Honey bee species dominated orchard communities, while other managed/manageable and wild species were collected in lower numbers. Moreover, the presence of herbaceous, uncultivated open areas and organic management practices were associated with increased wild bee diversity. Overall, our study sheds light on the importance of large-scale analyses contributing to the emerging fields of functional and phylogenetic diversity, which can be related to ecosystem function to promote biodiversity as a key asset in agroecosystems in the face of global change pressures.

Integrating digital pathology and mathematical modelling to predict spatial biomarker dynamics in cancer immunotherapy.

In oncology clinical trials, on-treatment biopsy samples are taken to confirm the mode of action of new molecules, among other reasons. Yet, the time point of sample collection is typically scheduled according to 'Expert Best Guess'. We have developed an approach integrating digital pathology and mathematical modelling to provide clinical teams with quantitative information to support this decision. Using digitised biopsies from an ongoing clinical trial as the input to an agent-based mathematical model, we have quantitatively optimised and validated the model demonstrating that it accurately recapitulates observed biopsy samples. Furthermore, the validated model can be used to predict the dynamics of simulated biopsies, with applications from protocol design for phase 1-2 studies to the conception of combination therapies, to personalised healthcare.

The Iliotibial Band: A Complex Structure with Versatile Functions.

The development of a pronounced iliotibial band (ITB) is an anatomically distinct evolution of humans. The mechanical behaviour of this "new" structure is still poorly understood and hotly debated in current literature. Iliotibial band syndrome (ITBS) is one of the leading causes of lateral knee pain injuries in runners. We currently lack a comprehensive understanding of the healthy behaviour of the ITB, and this is necessary prior to further investigating the aetiology of pathologies like ITBS. Therefore, the purpose of this narrative review was to collate the anatomical, biomechanical and clinical literature to understand how the mechanical function of the ITB is influenced by anatomical variation, posture and muscle activation. The complexity of understanding the mechanical function of the ITB is due, in part, to the presence of its two in-series muscles: gluteus maximus (GMAX) and tensor fascia latae (TFL). At present, we lack a fundamental understanding of how GMAX and TFL transmit force through the ITB and what mechanical role the ITB plays for movements like walking or running. While there is a range of proposed ITBS treatment strategies, robust evidence for effective treatments is still lacking. Interventions that directly target the running biomechanics suspected to increase either ITB strain or compression of lateral knee structures may have promise, but clinical randomised controlled trials are still required.

Escherichia coli contamination of lettuce sold at markets in Trinidad: A preliminary study

Objective: Historically most foodborne disease outbreaks have been attributed to animal products but recently the number of cases associated with vegetable produce has been increasing. Most of these microbial foodborne pathogens are also part of the resident gut flora of many animals and can be shed asymptomatically in the environment. Leafy greens contamination with these pathogens are of particular concern since they are consumed uncooked. Using Escherichia coli (E. coli) as an indicator of faecal contamination, we evaluated lettuce as a potential source of foodborne disease. Design and Methodology: A cross-sectional study was carried out targeting six retail markets in Trinidad. At each market, a total of 15 lettuce samples were purchased from five retailers. The E. coli colony forming units per gram (CFU/g) of lettuce were then assessed using standard laboratory techniques. Results: All farmers surveyed reported using pipe-borne water as their primary source of irrigation water. E. coli was present in all samples. Overall, the E. coli counts ranged from 0.8 to 80,000 CFU/gram. The lettuce E. coli counts varied with location (p=0.01) and was highest in San Fernando (3.4 ± 1.1 Log10CFU/g) and lowest in Marabella (1.5 ± 0.65 Log10 CFU/g). Interestingly, lettuce farms using manure had lower E. coli counts than those not using manure (2.88 ± 1.3 Log10 CFU/g vs 2.27±1.23 Log10 CFU/g; p=0.07.) Conclusion: These high E.coli counts are indicative of either preharvest or post-harvest faecal contamination of lettuce. The high level of E. coli contamination of lettuce being sold at market should be of serious concern since this a potential risk to public health.

Modeling Longitudinal Preclinical Tumor Size Data to Identify Transient Dynamics in Tumor Response to Antiangiogenic Drugs.

Experimental evidence suggests that antiangiogenic therapy gives rise to a transient window of vessel normalization, within which the efficacy of radiotherapy and chemotherapy may be enhanced. Preclinical experiments that measure components of vessel normalization are invasive and expensive. We have developed a mathematical model of vascular tumor growth from preclinical time-course data in a breast cancer xenograft model. We used a mixed-effects approach for model parameterization, leveraging tumor size data to identify a period of enhanced tumor growth that could potentially correspond to the transient window of vessel normalization. We estimated the characteristics of the window for mice treated with an anti-VEGF antibody (bevacizumab) or with a bispecific anti-VEGF/anti-angiopoietin-2 antibody (vanucizumab). We show how the mathematical model could theoretically be used to predict how to coordinate antiangiogenic therapy with radiotherapy or chemotherapy to maximize therapeutic effect, reducing the need for preclinical experiments that directly measure vessel normalization parameters.

Vascular phenotype identification and anti-angiogenic treatment recommendation: A pseudo-multiscale mathematical model of angiogenesis.

The development of anti-angiogenic drugs for cancer therapy has yielded some promising candidates, but novel approaches for interventions to angiogenesis have led to disappointing results. In addition, there is a shortage of biomarkers that are predictive of response to anti-angiogenic treatments. Consequently, the complex biochemical and physiological basis for tumour angiogenesis remains incompletely understood. We have adopted a mathematical approach to address these issues, formulating a spatially averaged multiscale model that couples the dynamics of VEGF, Ang1, Ang2 and PDGF, with those of mature and immature endothelial cells and pericyte cells. The model reproduces qualitative experimental results regarding pericyte coverage of vessels after treatment by anti-Ang2, anti-VEGF and combination anti-VEGF/anti-Ang2 antibodies. We used the steady state behaviours of the model to characterise angiogenic and non-angiogenic vascular phenotypes, and used mechanistic perturbations representing hypothetical anti-angiogenic treatments to generate testable hypotheses regarding transitions to non-angiogenic phenotypes that depend on the pre-treatment vascular phenotype. Additionally, we predicted a synergistic effect between anti-VEGF and anti-Ang2 treatments when applied to an immature pre-treatment vascular phenotype, but not when applied to a normalised angiogenic pre-treatment phenotype. Based on these findings, we conclude that changes in vascular phenotype are predicted to be useful as an experimental biomarker of response to treatment. Further, our analysis illustrates the potential value of non-spatial mathematical models for generating tractable predictions regarding the action of anti-angiogenic therapies.

Who's challenging who? Changing attitudes towards those whose behaviour challenges.

BACKGROUND: Although staff attitudes towards individuals with intellectual disability (ID) whose behaviour challenges may be an important part of a positive support culture, very little research has focused on the development of training specifically designed to change staff attitudes. Positive contact is hypothesised to be an effective way to change attitudes towards stigmatised groups. METHODS: We designed and developed a half day training package about the experiences of individuals whose behaviour challenges - Who's Challenging Who (WCW). The WCW package was delivered according to a manual by a trainer with ID and a professional without disability. Seventy-six staff from a variety of organisations participated in one of 10 WCW training sessions and provided data on their attitudes and empathy towards individuals whose behaviour challenges prior to the WCW training and immediately at the end of training. Staff also completed a post-training evaluation questionnaire. RESULTS: A training package was successfully developed collaboratively with individuals whose behaviour challenges, and received very positive evaluations from staff participants. Short-term positive change was shown for empowerment and similarity attitudes, and staff empathy and self-efficacy. These outcomes were associated with small to moderate effect sizes. CONCLUSIONS: Meaningful short-term positive staff attitude changes were found and the WCW training model was shown to be feasible. More robust research designs are needed for future evaluation. In addition, the function of an attitude change intervention such as WCW within organisations' training strategies requires further development.

Expression of D-serine and glycine transporters in the prefrontal cortex and cerebellum in schizophrenia.

The NMDA receptor co-agonists D-serine and glycine are thought to contribute to glutamatergic dysfunction in schizophrenia. They are removed from the synapse by specific neuronal and glial transporters, the status of which is clearly relevant to theories of D-serine and glycine function in the disorder. D-serine is primarily transported by Asc-1, and glycine by GlyT1 but maybe also by SNAT2. As a first step to addressing this issue, we studied Asc-1, GlyT1 and SNAT2 expression in dorsolateral prefrontal cortex and cerebellum of 18 subjects with schizophrenia and 20 controls, using immunoblotting and in situ hybridization. Asc-1 protein and SNAT2 mRNA were decreased in schizophrenia in both regions. GlyT1 mRNA and protein, and Asc-1 mRNA, were not altered. Antipsychotic administration for 14 days did not alter expression of the genes in rat brain. Unchanged GlyT1 suggests that glycine transport is not markedly affected in schizophrenia, and therefore that increased synaptic removal is not the basis for the putative deficit in glycine modulation of NMDA receptors in the disorder. Lowered Asc-1 in schizophrenia implies that D-serine reuptake is reduced, perhaps as a response to decreased synaptic D-serine availability. However, this interpretation remains speculative. Further investigations will be valuable in the evaluation of these transporters as potential therapeutic targets in psychosis.

Evaluation of IS900-PCR assay for detection of Mycobacterium avium subspecies Paratuberculosis infection in cattle using quarter milk and bulk tank milk samples.

A study was conducted to evaluate sensitivity, specificity, and predictive value of IS900-PCR assay for detection of Mycobacterium avium subspecies paratuberculosis in pooled quarter milk and bulk tank milk. Feces, blood and pooled quarter milk from 1493 lactating cattle on 29 herds were analyzed. Bulk tank milk (n = 29 bulk tanks) samples were also examined. Culture analysis revealed that 10.9%, 2.8%, and 20.6% of fecal, pooled quarter milk samples and bulk tanks were positive for M. avium subsp. paratuberculosis, respectively. While 13.5% and 27.5% of pooled quarter milk samples and bulk tanks were positive by IS900 PCR assay, respectively. Moderate to high antibody titers for M. avium subsp. paratuberculosis were detected in 223 of 1493 (14.4%) cows. Cows positive on fecal culture were taken as true positives relative to which the IS900 PCR assay was evaluated. The sensitivity and predictive value of KELA, pooled quarter milk culture, and IS900 PCR assay increased with lactation age. While the specificity of the tests decreased with increase in lactation age. Overall, the IS900 PCR assay using pooled quarter milk samples had a sensitivity, specificity and predictive value of 0.87, 0.95 and 0.71, respectively. The IS900 PCR assay using bulk tank milk had poor sensitivity (0.21), specificity (0.5) and predictive value (0.6). Pooled quarter milk culture analysis had a very low sensitivity (0.17). The kinetics ELISA had lower sensitivity (0.59), specificity (0.90) and predictive value (0.43) as compared to the IS900 PCR assay using pooled quarter milk samples. Results from our study suggest that IS900 PCR assay using bulk tank milk may not be useful for screening herds with M. avium subsp. paratuberculosis infected animals. In conclusion, use of IS900 PCR assay for cows in 2(nd) lactation and higher, using aseptically collected pooled quarter milk samples, can be a useful tool for screening and monitoring lactating cattle in herds with M. avium subsp. paratuberculosis infection.

Client satisfaction in a feasibility study comparing face-to-face interviews with telepsychiatry.

We carried out a pilot study comparing satisfaction levels between psychiatric patients seen face to face (FTF) and those seen via videoconference. Patients who consented were randomly assigned to one of two groups. One group received services in person (FTF from the visiting psychiatrist) while the other was seen using videoconferencing at 128 kbit/s. One psychiatrist provided all the FTF and videoconferencing assessment and follow-up visits. A total of 24 subjects were recruited. Three of the subjects (13%) did not attend their appointments and two subjects in each group were lost to follow-up. Thus there were nine in the FTF group and eight in the videoconferencing group. The two groups were similar in most respects. Patient satisfaction with the services was assessed using the Client Satisfaction Questionnaire (CSQ-8), completed four months after the initial consultation. The mean scores were 25.3 in the FTF group and 21.6 in the videoconferencing group. Although there was a trend in favour of the FTF service, the difference was not significant. Patient satisfaction is only one component of evaluation. The efficacy of telepsychiatry must also be measured relative to that of conventional, FTF care before policy makers can decide how extensively telepsychiatry should be implemented.

BAG-1 is a novel cytoplasmic binding partner of the membrane form of heparin-binding EGF-like growth factor: a unique role for proHB-EGF in cell survival regulation.

Several cell functions related to growth and survival regulation have been attributed specifically to the membrane form of heparin-binding EGF-like growth factor (proHB-EGF), rather than to the diffusible, processed HB-EGF isoform. These findings suggest the existence of a functional binding partner specifically for the membrane form of the growth factor. In this study we have identified the prosurvival cochaperone, BAG-1, as a protein that interacts with the cytoplasmic tail domain of proHB-EGF. Interaction between BAG-1 and the 24-amino acid proHB-EGF cytoplasmic tail was initially identified in a yeast two-hybrid screen and was confirmed in mammalian cells. The proHB-EGF tail bound BAG-1 in an hsp70-independent manner and within a 97-amino acid segment that includes the ubiquitin homology domain in BAG-1 but does not include the hsp70 binding site. Effects of BAG-1 and proHB-EGF co-expression were demonstrated in cell adhesion and cell survival assays and in quantitative assays of regulated secretion of soluble HB-EGF. Because the BAG-1 binding site is not present on the mature, diffusible form of the growth factor, these findings suggest a new mechanism by which proHB-EGF, in isolation from the diffusible form, can mediate cell signaling events. In addition, because effects of BAG-1 on regulated secretion of soluble HB-EGF were also identified, this interaction has the potential to alter the signaling capabilities of both the membrane-anchored and the diffusible forms of the growth factor.

C-terminal variations in beta-thymosin family members specify functional differences in actin-binding properties.

Mammalian cells express several isoforms of beta-thymosin, a major actin monomer sequestering factor, including thymosins beta4, beta10, and beta15. Differences in actin-binding properties of different beta-thymosin family members have not been investigated. We find that thymosin beta15 binds actin with a 2.4-fold higher affinity than does thymosin beta4. Mutational analysis was performed to determine the amino acid differences in thymosin beta15 that specify its increased actin-affinity. Previous work with thymosin beta4 identified an alpha-helical domain, as well as a conserved central motif, as crucial for actin binding. Mutational analysis confirms that these domains are also vital for actin binding in thymosin beta15, but that differences in these domains are not responsible for the variation in actin-binding properties between thymosins beta4 and beta15. Truncation of the unique C-terminal residues in thymosin beta15 inhibits actin binding, suggesting that this domain also has an important role in mediating actin-binding affinity. Replacement of the 10 C-terminal amino acids of thymosin beta15 with those of thymosin beta4 did, however, reduce the actin-binding affinity of the hybrid relative to thymosin beta15. Similarly, replacement of the thymosin beta4 C-terminal amino acids with those of thymosin beta15 led to increased actin binding. We conclude that functional differences between closely related beta-thymosin family members are, in part, specified by the C-terminal variability between these isoforms. Such differences may have consequences for situations where beta-thymosins are differentially expressed as in embryonic development and in cancer.

Genetic analysis of the Utah population: a comparison of STR and VNTR loci.

Genetic data are reported for nine short tandem repeat (STR) loci (D3S1358, vWA, FGA, D8S1179, D21S11, D18S51, D5S818, D13S317, and D7S820) and six variable number of tandem repeat (VNTR) loci (D2S44, D10S28, D4S139, D1S7, D5S110, and D17S79) in samples of Utah African Americans, European Americans, and Hispanics. Little evidence of departures from Hardy-Weinberg equilibrium or gametic equilibrium was found in these populations. Because of their relatively higher mutation rates, the VNTR loci exhibited higher average heterozygosity and lower FST levels than did the STR loci. Genetic distance analysis showed congruence between the two types of systems, and a genetic distance analysis of the STR data showed that the three Utah populations are genetically similar to the same ethnic groups in other parts of the United States. In addition, this analysis showed that the African American population is the most genetically divergent, with greater similarity between the Hispanic and European American populations. This analysis demonstrates a high degree of consistency for population designations commonly used in forensic analysis.

Is the obstetric guideline of 30 minutes from decision to incision for Cesarean delivery clinically significant?

A Cesarean delivery may be critical to the health and wellbeing of a newborn. The time required to extract an infant from a hostile in utero environment is a frequent issue in medical negligence cases. The American College of Obstetricians and Gynecologists and the American Academy of Pediatrics suggest a time guideline of 30 minutes from decision for Cesarean delivery to the beginning (incision) of the procedure. This time frame is based on survey data from hospitals throughout the United States and is not based on clinical outcomes or the pathophysiology of obstetric events. This review focuses on specific Cesarean indications as noted by the specialty groups and analyzes them from an outcome point of view. The authors conclude that specific high-risk factors do indeed warrant delivery in as expedient a fashion as possible; however, compliance with the 30-minute guideline does not necessarily lead to a difference in outcome as far as the neonate is concerned.

A case-control study of diet and testicular carcinoma.

No risk factor other than cryptorchidism has been consistently associated with testicular cancer, and the influence of diet on testicular cancer risk has not been extensively explored. A few studies have found increased testicular cancer risk in men whose diets are high in fat, red meats, and milk or low in fruits and vegetables. We evaluated the relationship of dietary factors and risk of testicular cancer and also examined whether this risk varied by type of testicular cancer. We conducted a hospital-based case-control study at The University of Texas M. D. Anderson Cancer Center (Houston, TX) of 160 testicular cancer cases diagnosed between 1990 and 1996 and 136 friend-matched controls. The results of multivariable logistic regression analysis showed that after adjustment for age, education, income, ethnicity, cryptorchidism, and total daily calories, increasing total fat, saturated fat, and cholesterol consumption were associated with increasing risk of nonseminoma testicular cancer, with odds ratios (ORs) for the highest vs. the lowest quartiles of 6.3, 5.3, and 4.6, respectively. The risk for seminoma testicular cancer marginally increased with increasing intake of total fat and saturated fat, with ORs for the highest vs. lowest quartiles of 1.9 and 2.1, respectively. Higher total fat consumption was nearly significantly related to increased mixed germ cell tumor risk, with an OR for highest vs. lowest quartile of 4.2. This study supports the hypothesis that diet (particularly high fat consumption) increases testicular cancer risk in young men. However, the small sample size and the possibility that these observations may be due to bias indicate that the relationship of diet and testicular cancer risk needs to be further examined within a prospective or incident case-control study.

Interaction of axin and Dvl-2 proteins regulates Dvl-2-stimulated TCF-dependent transcription.

Axin promotes the phosphorylation of beta-catenin by GSK-3beta, leading to beta-catenin degradation. Wnt signals interfere with beta-catenin turnover, resulting in enhanced transcription of target genes through the increased formation of beta-catenin complexes containing TCF transcription factors. Little is known about how GSK-3beta-mediated beta-catenin turnover is regulated in response to Wnt signals. We have explored the relationship between Axin and Dvl-2, a member of the Dishevelled family of proteins that function upstream of GSK-3beta. Expression of Dvl-2 activated TCF-dependent transcription. This was blocked by co-expression of GSK-3beta or Axin. Expression of a 59 amino acid GSK-3beta-binding region from Axin strongly activated transcription in the absence of an upstream signal. Introduction of a point mutation into full-length Axin that prevented GSK-3beta binding also generated a transcriptional activator. When co-expressed, Axin and Dvl-2 co-localized within expressing cells. When Dvl-2 localization was altered using a C-terminal CAAX motif, Axin was also redistributed, suggesting a close association between the two proteins, a conclusion supported by co-immunoprecipitation data. Deletion analysis suggested that Dvl-association determinants within Axin were contained between residues 603 and 810. The association of Axin with Dvl-2 may be important in the transmission of Wnt signals from Dvl-2 to GSK-3beta.