Synchronous primary cutaneous melanomas: a descriptive study of their clinical features, histology, genetic background of the patients and clinical outcomes.

BACKGROUND: Around 0.5% of cutaneous melanoma (CM) patients will present with synchronous melanomas when first seen. Moreover, 26-40% of patients with multiple primary melanomas present with synchronous lesions. OBJECTIVES: To assess the prevalence, clinical and histopathological characteristics, germline mutations and outcome in patients with synchronous melanoma. METHODS: Clinical and histopathological data from 4703 melanoma patients were included. Clinical, histological and genetic mutational status information was analysed. Kaplan-Meier curves were used to investigate survival outcomes. RESULTS: A total of 144 patients (3.06%) presented simultaneously with two or more primary melanomas. During follow-up, 25.7% of patients with synchronous melanoma developed a new primary melanoma compared to 8.6% of patients diagnosed with single melanoma (P < 0.001). Germinal CDKN2A mutations were identified in 10.7% of patients with synchronous melanomas and genetic variants in MC1R in 72%. No significant differences in all survival outcomes between patients with synchronous melanomas and single melanomas were found. CONCLUSION: Synchronous melanomas are more frequent than previously reported and are more frequent in older patients compared to single melanomas. Moreover, these patients have a higher risk of developing a new primary melanoma during follow-up and have higher rates of germline susceptibility variants. Nevertheless, these findings were not associated with worse outcomes.

Comparison of two primer-probe sets of Fusobacterium nucleatum using droplet digital polymerase chain reaction for the detection of colorectal neoplasia from faecal samples.

BACKGROUND: Although faecal DNA testing of Fusobacterium nucleatum (Fn) is expected to be useful for colorectal neoplasia detection, there is no standardized quantification method of Fn. We performed this study to establish a possible standardized method. METHODS: In this study, 322 participants including 71 subjects without colorectal neoplasia (control group), 31 patients with non-advanced colorectal adenoma, 93 patients with advanced colorectal adenoma, and 127 patients with colorectal cancer were enrolled. Faecal Fn were quantified by droplet digital PCR (ddPCR) using two PCR primer-probe sets reported previously that are tentatively named Fn1 and Fn2. Fn1 has been used in ddPCR by us and Fn2 has been widely used in quantitative real-time PCR. RESULTS: The Fn copy number using Fn1 was five times higher than that using Fn2, with a linear relationship shown between them. Receiver operating characteristic curve analysis showed the area under the curve (AUC) to be almost the same between Fn1 and Fn2 in discriminating between the control group and the colorectal cancer group (AUC = 0.81 and 0.81, respectively), and between the control/non-advanced colorectal adenoma group and the advanced colorectal adenoma/colorectal cancer group (AUC = 0.74 and 0.74, respectively). CONCLUSIONS: As the diagnostic performance was quite similar between Fn1 and Fn2, ddPCR-based Fn testing using Fn1 and Fn2 could be a possible standardized method for a colorectal neoplasia screening test, considering that Fn levels quantified by Fn1 are about five times higher than those by Fn2.

Precarious work among personal support workers in the Greater Toronto Area: a respondent-driven sampling study.

BACKGROUND: The COVID-19 pandemic has highlighted the role of personal support workers (PSWs) in health care, as well as their work conditions. Our study aimed to understand the characteristics of the PSW workforce, their work conditions and their job security, as well as to explore the health of PSWs and the impact of precarious employment on their health. METHODS: Our community-based participatory action research focused on PSWs in the Greater Toronto Area. We administered an online, cross-sectional survey between June and December 2020 using respondent-driven sampling. Data on sociodemographics, employment precarity, worker empowerment and health status were collected. We assessed the association between precarious employment and health using multivariable logistic regression models. RESULTS: We contacted 739 PSWs, and 664 consented to participate. Overall, 658 (99.1%) completed at least part of the survey. Using data adjusted for our sampling approach, the participants were predominantly Black (76.5%, 95% confidence interval [CI] 68.2%-84.9%), women (90.1%, 95% CI 85.1%-95.1%) and born outside of Canada (97.4%, 95% CI 94.9%-99.9%). Most worked in home care (43.9%, 95% CI 35.2%-52.5%) or long-term care (34.5%, 95% CI 27.4%-42.0%). Although most participants had at least some postsecondary education (unadjusted proportion = 83.4%, n = 529), more than half were considered low income (55.1%, 95% CI 46.3%-63.9%). Most participants were precariously employed (86.5%, 95% CI 80.7%-92.4%) and lacked paid sick days (89.5%, 95% CI 85.8%-93.3%) or extended health benefits (74.1%, 95% CI 66.8%-81.4%). Nearly half of the participants described their health as less than very good (46.7%, 95% CI 37.9%-55.5%). Employment precarity was significantly associated with higher risk of depression (odds ratio 1.02, 95% CI 1.01-1.03). INTERPRETATION: Despite being key members of health care teams, most PSWs were precariously employed with low wages that keep them in poverty; the poor work conditions they faced could be detrimental to their physical and mental health. Equitable strategies are needed to provide decent work conditions for PSWs and to improve their health.

The working conditions for personal support workers in the Greater Toronto Area during the COVID-19 pandemic: a mixed-methods study.

OBJECTIVE: During the height of the COVID-19 pandemic, personal support workers (PSWs) were heralded as healthcare 'heroes' as many of them cared for high-risk, vulnerable older populations, and worked in long-term care, which experienced a high number of COVID-19 outbreaks and deaths. While essential to the healthcare workforce, there is little understanding of PSW working conditions during the pandemic. The aim of our study was to examine the working conditions (including job security, work policies, and personal experiences) for PSWs in the Greater Toronto Area during the COVID-19 pandemic from the perspectives of PSWs. METHODS: This study used a mixed-methods design. From June to December 2020, we conducted a survey of 634 PSWs to understand their working conditions during the COVID-19 pandemic. Semi-structured interviews with 31 survey respondents were conducted from February to May 2021 to understand in greater depth how working conditions were impacting the well-being of PSWs. RESULTS: We found PSWs faced a range of challenges related to COVID-19, including anxiety about contracting COVID-19, reduced work hours, taking leaves of absences, concerns about job security, and losing childcare. While the COVID-19 pandemic highlighted the PSW workforce and their importance to the healthcare system (especially in the long-term care system), pre-existing poor work conditions of insecure jobs with no paid sick days and benefits exacerbated COVID-19-related challenges. Despite these hardships, PSWs were able to rely on their mental resilience and passion for their profession to cope with challenges. CONCLUSION: Significant changes need to be made to improve PSW working conditions. Better compensation, increased job security, decreased workload burden, and mental health supports are needed.

RéSUMé: OBJECTIF: Au plus fort de la pandémie de COVID-19, les préposés aux bénéficiaires (PAB) étaient salués comme les « héros ¼ des soins de santé, car beaucoup s'occupaient de populations vulnérables et âgées à risque élevé et travaillaient dans le milieu des soins de longue durée, qui était aux prises avec un grand nombre d'éclosions de COVID-19 et de décès. Malgré l'importance névralgique des PAB dans la main-d'œuvre des soins de santé, leurs conditions de travail durant la pandémie sont peu connues. Nous avons cherché à examiner les conditions de travail (sécurité d'emploi, régimes de travail et expériences personnelles) des PAB dans la région du Grand Toronto durant la pandémie de COVID-19 selon la perspective de ces PAB. MéTHODE: Nous avons utilisé un plan d'étude à méthodes mixtes. De juin à décembre 2020, nous avons sondé 634 PAB pour connaître leurs conditions de travail durant la pandémie de COVID-19. Des entretiens semi-directifs ont été menés auprès de 31 répondants et répondantes entre les mois de février et de mai 2021 pour approfondir notre compréhension de l'impact des conditions de travail des PAB sur leur bien-être. RéSULTATS: Nous avons constaté que les PAB ont connu de nombreuses difficultés en lien avec la COVID-19, dont l'anxiété à l'idée de transmettre la COVID-19, les heures de travail réduites, la prise de congés, les craintes pour leur sécurité d'emploi et la perte de services de garde. Bien que la pandémie de COVID-19 ait braqué les projecteurs sur les PAB et leur importance pour le système de soins de santé (surtout dans le système de soins de longue durée), leurs mauvaises conditions de travail préexistantes ­ des emplois précaires sans congés de maladie payés ni avantages sociaux ­ ont exacerbé les problèmes posés par la COVID-19. Malgré ces épreuves, les PAB ont pu compter sur leur résilience mentale et leur passion pour la profession pour faire face aux difficultés. CONCLUSION: D'importants changements doivent être apportés pour améliorer les conditions de travail des PAB. De meilleurs salaires, une plus grande sécurité d'emploi, une charge de travail allégée et des mesures d'appui à la santé mentale sont nécessaires.

Podocyte GSK3α is important for autophagy and its loss detrimental for glomerular function.

Podocytes are key cells in maintaining the integrity of the glomerular filtration barrier and preventing albuminuria. Glycogen synthase kinase 3 (GSK3) is a multi-functional serine/threonine kinase existing as two distinct but related isoforms (α and ß). In the podocyte it has previously been reported that inhibition of the ß isoform is beneficial in attenuating a variety of glomerular disease models but loss of both isoforms is catastrophic. However, it is not known what the role of GSK3α is in these cells. We now show that GSK3α is present and dynamically modulated in podocytes. When GSK3α is transgenically knocked down specifically in the podocytes of mice it causes mild but significant albuminuria by 6-weeks of life. Its loss also does not protect in models of diabetic or Adriamycin-induced nephropathy. In vitro deletion of podocyte GSK3α causes cell death and impaired autophagic flux suggesting it is important for this key cellular process. Collectively this work shows that GSK3α is important for podocyte health and that augmenting its function may be beneficial in treating glomerular disease.

Building the political case for investing in public health and public health research.

Governments around the world vastly underinvest in public health, despite ever growing evidence demonstrating its economic and social benefits. Challenges in securing greater public health investment largely stem from the necessity for governments to demonstrate visible impacts within an election cycle, whereas public health initiatives operate over the long term and generally involve prevention, statistical lives and underlying conditions. It is time for the public health community to rethink its strategies and craft political wins by building a political case for investing in public health-which extends far beyond mere economic and social arguments. These strategies need to make public health visible, account for the complexities of policymaking networks and adapt knowledge translation efforts to the appropriate policy instrument.

Work Disability Management Communication Bottlenecks Within Large and Complex Public Service Organizations: A Sociotechnical Systems Study.

Purpose Within large and complex organizations work disability (WD) communication bottlenecks emerge and contribute to avoidable disability days. Our study utilized soft systems methods to better understand communication problems in WD management. Methods Semi-structured interviews were conducted with disability case managers (n = 10), frontline supervisors (n = 15) and human resource/labor relations specialists (n = 5) within three public service organizations. Interview questions asked about organizational WD system structure and communication practices. Thematic analysis was conducted to examine system structure and emergent communication bottlenecks. Results WD communication took place across a number of internal and external stakeholders. Communication bottlenecks tended to concentrate within WD case manager and frontline supervisor activities. Inconsistent communication across organizations, challenges interacting with external stakeholders, mental health disability information exchange, lack of WD communication experience and previous worker performance represented communication bottlenecks that contributed to avoidable disability days. Conclusions To strengthen communication practices, systems-focused responses towards organizational WD management are required.

Podocyte GSK3 is an evolutionarily conserved critical regulator of kidney function.

Albuminuria affects millions of people, and is an independent risk factor for kidney failure, cardiovascular morbidity and death. The key cell that prevents albuminuria is the terminally differentiated glomerular podocyte. Here we report the evolutionary importance of the enzyme Glycogen Synthase Kinase 3 (GSK3) for maintaining podocyte function in mice and the equivalent nephrocyte cell in Drosophila. Developmental deletion of both GSK3 isoforms (α and ß) in murine podocytes causes late neonatal death associated with massive albuminuria and renal failure. Similarly, silencing GSK3 in nephrocytes is developmentally lethal for this cell. Mature genetic or pharmacological podocyte/nephrocyte GSK3 inhibition is also detrimental; producing albuminuric kidney disease in mice and nephrocyte depletion in Drosophila. Mechanistically, GSK3 loss causes differentiated podocytes to re-enter the cell cycle and undergo mitotic catastrophe, modulated via the Hippo pathway but independent of Wnt-ß-catenin. This work clearly identifies GSK3 as a critical regulator of podocyte and hence kidney function.

The occupational health and safety vulnerability of recent immigrants accessing settlement services.

OBJECTIVE: To compare occupational health and safety (OHS) vulnerability of recent Canadian immigrants and workers born in Canada. METHODS: Recent immigrants (n = 195) were recruited at four settlement agencies in Southern Ontario, and non-immigrants in Ontario (n = 1030) were contacted by phone and email by a third-party survey provider. The questionnaire measured OHS vulnerability using a 27-item measure and collected sociodemographic and workplace information. Responses were used to evaluate one overall and three specific (policy and procedure, awareness, and empowerment) measures of OHS vulnerability. Log-binomial models compared the overall and policy and procedure-, awareness- and empowerment-related vulnerability of recent immigrants to non-immigrant workers. Models were adjusted for demographic and workplace characteristics. RESULTS: New immigrants experience statistically elevated levels of overall (adjusted risk ratio [ARR] = 1.60, 95% CI 1.23-2.07) and empowerment-related vulnerability (ARR = 1.54, 95% CI 1.09-2.17). Compared to workers born in Canada, immigrants also report elevated levels of policy and procedure vulnerability (ARR = 1.37, 95% CI 0.98-1.92), although this estimate did not meet traditional criteria for statistical significance. CONCLUSIONS: This study uses a novel multi-dimensional measure to identify how differences in workplace context place recent immigrant workers at increased risk of work-related injury or illness. Recent immigrant workers experience increased risk of OHS vulnerability. In particular, this vulnerability results from exposure to hazards in combination with inadequate levels of empowerment to protect themselves in the workplace. Policy-makers, advocates, and employers should implement strategies that not only build workplaces where occupational hazards are minimized but also ensure immigrant workers are empowered to act on their workplace rights and engaged to improve workplace safety.

Examining occupational health and safety vulnerability among Canadian workers with disabilities.

OBJECTIVE: To compare workers with and without disabilities on their reported workplace hazard exposure and the presence of occupational health and safety vulnerability factors. METHODS: Working-aged adults in Ontario or British Columbia were recruited to participate in a cross-sectional survey (n = 1988). Self-reported measures included demographic factors, work-related variables, perceived level of activity limitation at work, and presence of work safety vulnerability factors utilizing a novel framework. RESULTS: Reporting a disability at work was significantly associated with greater hazard exposure than those without a disability. In addition, those reporting a disability at work were more likely to be employed in conditions where hazard exposure was combined with inadequate policies and procedures, or hazard exposures were combined with inadequate empowerment. CONCLUSIONS: Work safety vulnerability is one way that health inequalities can be perpetuated even among those with disabilities who have found work. Our results suggest that employers and policy makers need to focus on assessing and addressing hazard exposures and targeting occupational health and safety resources in the workplace in a way that includes workers with disabilities. Implications for Rehabilitation Workers with disabilities experience greater hazard exposure than those without a disability. Those with moderate and severe disabilities reported occupational health and safety vulnerability, suggesting that workplace accommodations should be available to a broader range of disability levels. It appears that, above and beyond standard safety procedures, providing workplace accommodations for people with disabilities may further reduce their hazard exposure and improve their safety.

Individual, occupational, and workplace correlates of occupational health and safety vulnerability in a sample of Canadian workers.

OBJECTIVE: To describe OH&S vulnerability across a diverse sample of Canadian workers. METHODS: A survey was administered to 1,835 workers employed more than 15 hrs/week in workplaces with at least five employees. Adjusted logistic models were fitted for three specific and one overall measure of workplace vulnerability developed based on hazard exposure and access to protective OH&S policies and procedures, awareness of employment rights and responsibilities, and workplace empowerment. RESULTS: More than one third of the sample experienced some OH&S vulnerability. The type and magnitude of vulnerability varied by labor market sub-group. Younger workers and those in smaller workplaces experienced significantly higher odds of multiple types of vulnerability. Temporary workers reported elevated odds of overall, awareness- and empowerment-related vulnerability, while respondents born outside of Canada had significantly higher odds of awareness vulnerability. CONCLUSION: Knowing how labor market sub-groups experience different types of vulnerability can inform better-tailored primary prevention interventions.

Population pharmacokinetic analysis of diurnal and seasonal variations of plasma concentrations of cilostazol in healthy volunteers.

BACKGROUND: The background of this study was (1) to examine factors influencing cilostazol pharmacokinetics by developing a population model incorporating diurnal variation and other covariate effects and (2) to assess the feasibility of applying the developed model to determine the optimal dosing times. METHODS: Data obtained from a cilostazol pharmacokinetic study consisting of 2 clinical trials (a single twice-a-day (BID) dosing trial in winter and a multiple BID dosing trial in summer) conducted in healthy Korean subjects were used for model building. A basic model was built, followed by a diurnal variation model, and then a final model was built incorporating covariates, including a seasonal difference. The optimal morning and evening dosing times were determined from simulations. RESULTS: Diurnal variation in cilostazol pharmacokinetics was explained by the morning absorption rate constant being faster than in the evening, yielding values of 0.278 versus 0.234/h in summer, when 24- and 12-hour circadian rhythms were included in the model. The seasonal variation was explained by a 26.9% and a 31.8% decrease in the absorption rate constant and clearance, respectively, in winter compared with summer. Based on twice-a-day (BID) dosing, dosing times of 9 AM and 5 PM in summer and 10 AM and 7 PM in winter were expected to produce the smallest peak-to-peak fluctuations in cilostazol concentration, possibly minimizing unwanted effects of the drug. CONCLUSIONS: This study demonstrated the intraday and interseasonal time-varying nature of cilostazol pharmacokinetics using a population modeling approach and developed a strategy for optimizing dosing times. It is suggested that these methods can be similarly applied to analyses and controls of other drugs that exhibit characteristics of time-varying pharmacokinetics.

WNT7B mediates autocrine Wnt/ß-catenin signaling and anchorage-independent growth in pancreatic adenocarcinoma.

Developmental and cancer models show Wnt/ß-catenin-dependent signaling mediates diverse phenotypic outcomes in the pancreas that are dictated by context, duration and strength of activation. While generally assumed to be pro-tumorigenic, it is unclear to what extent dysregulation of Wnt/ß-catenin signaling impacts tumor progression in pancreatic adenocarcinoma (PDAC). In the present study, Wnt/ß-catenin activity was characterized across a spectrum of PDAC cell lines and primary tumors. Reporter and gene expression-based assays revealed wide heterogeneity in Wnt/ß-catenin transcriptional activity across PDAC cell lines and patient tumors, as well as variable responsiveness to exogenous Wnt ligand stimulation. An experimentally generated, pancreas-specific gene expression signature of Wnt/ß-catenin transcriptional activation was used to stratify pathway activation across a cohort of resected, early-stage PDAC tumors (N=41). In this cohort, higher Wnt/ß-catenin activation was found to significantly correlate with lymphvascular invasion and worse disease-specific survival (median survival time 20.3 versus 43.9 months, log-rank P=0.03). Supporting the importance of Wnt ligand in mediating autocrine Wnt signaling, Wnt/ß-catenin activity was significantly inhibited in PDAC cell lines by WLS gene silencing and the small-molecule inhibitor IWP-2, both of which functionally block Wnt ligand processing and secretion. Transcriptional profiling revealed elevated expression of WNT7B occurred in PDAC cell lines with high levels of cell autonomous Wnt/ß-catenin activity. Gene-knockdown studies in AsPC-1 and HPAF-2 cell lines confirmed WNT7B-mediated cell autonomous Wnt/ß-catenin activation, as well as an anchorage-independent growth phenotype. Our findings indicate WNT7B can serve as a primary determinant of differential Wnt/ß-catenin activation in PDAC. Disrupting the interaction between Wnt ligands and their receptors may be a particularly suitable approach for therapeutic modulation of Wnt/ß-catenin signaling in PDAC and other cancer contexts where Wnt activation is mediated by ligand expression rather than mutations in canonical pathway members.

Insulin directly stimulates VEGF-A production in the glomerular podocyte.

Podocytes are critically important for maintaining the integrity of the glomerular filtration barrier and preventing albuminuria. Recently, it has become clear that to achieve this, they need to be insulin sensitive and produce an optimal amount of VEGF-A. In other tissues, insulin has been shown to regulate VEGF-A release, but this has not been previously examined in the podocyte. Using in vitro and in vivo approaches, in the present study, we now show that insulin regulates VEGF-A in the podocyte in both mice and humans via the insulin receptor (IR). Insulin directly increased VEGF-A mRNA levels and protein production in conditionally immortalized wild-type human and murine podocytes. Furthermore, when podocytes were rendered insulin resistant in vitro (using stable short hairpin RNA knockdown of the IR) or in vivo (using transgenic podocyte-specific IR knockout mice), podocyte VEGF-A production was impaired. Importantly, in vivo, this occurs before the development of any podocyte damage due to podocyte insulin resistance. Modulation of VEGF-A by insulin in the podocyte may be another important factor in the development of glomerular disease associated with conditions in which insulin signaling to the podocyte is deranged.

Measuring silver nanoparticle dissolution in complex biological and environmental matrices using UV-visible absorbance.

Distinguishing the toxic effects of nanoparticles (NPs) themselves from the well-studied toxic effects of their ions is a critical but challenging measurement for nanotoxicity studies and regulation. This measurement is especially difficult for silver NPs (AgNPs) because in many relevant biological and environmental solutions, dissolved silver forms AgCl NPs or microparticles. Simulations predict that solid AgCl particles form at silver concentrations greater than 0.18 and 0.58 µg/mL in cell culture media and moderately hard reconstituted water (MHRW), respectively. The AgCl NPs are usually not easily separable from AgNPs. Therefore, common existing total silver techniques applied to measure AgNP dissolution, such as inductively coupled plasma mass spectrometry (ICP-MS) or atomic absorption, cannot accurately measure the amount of silver remaining in AgNP form, as they cannot distinguish Ag oxidation states. In this work, we introduce a simple localized surface plasmon resonance (LSPR) UV-visible absorbance measurement as a technique to measure the amount of silver remaining in AgNP form for AgNPs with constant agglomeration states. Unlike other existing methods, this absorbance method can be used to measure the amount of silver remaining in AgNP form even in biological and environmental solutions containing chloride because AgCl NPs do not have an associated LSPR absorbance. In addition, no separation step is required to measure the dissolution of the AgNPs. After using ICP-MS to show that the area under the absorbance curve is an accurate measure of silver in AgNP state for unagglomerating AgNPs in non-chloride-containing media, the absorbance is used to measure dissolution rates of AgNPs with different polymer coatings in biological and environmental solutions. We find that the dissolution rate decreases at high AgNP concentrations, 5 kDa polyethylene glycol thiol coatings increase the dissolution rate, and the rate is much higher in cell culture media than in MHRW.

Bacillus subtilis (DSM17299) significantly reduces Salmonella in broilers.

Salmonella continues to be a major public health burden worldwide. Poultry are known to be one of the main reservoirs for this zoonotic pathogen. It has previously been shown that a single dose of Bacillus subtilis reduces fecal shedding of Salmonella enterica serovar Enteritidis, whereas no effect on long-term colonization of the cecum has been observed. Here we report experiments that were undertaken to test the efficacy of a conventional diet supplemented with a probiotic (B. subtilis DSM17299) on 1) Salmonella colonization in the intestinal tract of broiler chickens, and 2) fecal shedding of Salmonella under production-like conditions. The trial birds fed the B. subtilis diet showed a significant 58% reduction in Salmonella-positive drag swabs compared with control birds, which had 100% presence of Salmonella. Feeding B. subtilis significantly reduced the average Salmonella load of cecum samples of the chickens, by 3 log units. This reduction in Salmonella colonization might not only positively affect broilers on the live production side by reducing the risk of infection between birds, but could also aid on the processing side by decreasing the amount of Salmonella entering the facility and improving food safety. Furthermore, numerical, but not statistically significant, improvements in feed conversion rate and BW gain at d 42 were observed in the B. subtilis-treated group compared with control birds.

Antibody-mediated self-limiting self-assembly for quantitative analysis of nanoparticle surfaces by atomic force microscopy.

Quantification of very low density molecular coatings on large (60 nm) gold nanoparticles (AuNPs) is demonstrated via the use of antibody-mediated self-limiting self-assembly of small and large AuNPs into raspberry-like structures subsequently imaged by atomic force microscopy (AFM). AFM imaging is proposed as an automated, lower-cost, higher-throughput alternative to immunostaining and imaging by transmission electron microscopy. Synthesis of large AuNPs, containing one of three ligand molecules in one of three stoichiometries (1, 2, or 10 ligands per AuNP), and small probe AuNPs with one of three antibody molecules in a one antibody per AuNP ratio, enabled a range of predicted self-limiting self-assembled structures. A model predicting the probability of observing a given small to large AuNP ratio based on a topography measurement such as AFM is described, in which random orientational deposition is assumed and which accounts for the stochastic synthesis method of the library AuNPs with varied ligand ratios. Experimental data were found to agree very well with the predictive models when using an established AFM sample preparation method that avoids drying-induced aggregation.

Hot topic: Black spot defect in Cheddar cheese linked to intramammary teat sealant.

The objective of this work was to characterize a novel appearance defect found in Cheddar cheese, heretofore referred to as black spot defect (BSD), and to determine an etiology. Uniformly distributed throughout the cheese mass, BSD appears as small spherical black spots from 0.20 to 4.7 mm in diameter and at an average frequency of about 2 spots per kg of cheese. To date, BSD has only been found in aged Cheddar cheese. Selected elemental analysis found the BSD region in cheese to have average concentrations of the element bismuth of approximately 400 microg/g, representing an approximately 2,500-fold increase over native levels of bismuth in cheese. Transmission electron microscopy analysis of the BSD region revealed amorphous solid structures and one-dimensional hair-like structures, neither of which was present in non-BSD regions. Such amorphous "nanorod" structures can be formed by the crystallization of bismuth III sulfide and are proposed to be a source of black discoloration. We hypothesize that localized bismuth salts entrained within the cheese curd react with hydrogen sulfide generated during aging to generate bismuth III sulfide. We further propose that the presence of localized bismuth salt precursor results from residual levels of a commercial intra-mammary teat sealant containing bismuth subnitrate that becomes unintentionally entrained within the cheese milk.

Plantar foot pressure responses to changes during dynamic trans-tibial prosthetic alignment in a clinical setting.

Alignment of a lower limb prosthesis refers to the spatial orientation of the prosthetic components and socket with respect to one another. During the process of dynamic alignment, a prosthetist repeatedly modifies this spatial orientation and observes the amputee's resulting walking pattern, eventually arriving at an alignment that is judged to be optimal. Quantification of the effect of each alignment modification and correlation of the magnitude of modification with the changes in gait could improve understanding of the process and promote an evidential base for practice. This investigation quantified bilateral plantar foot pressures in six trans-tibial amputee subjects during the process of dynamic alignment at prosthetists' clinics during regularly scheduled appointments. Outcomes of changes in prosthetic alignment during the clinical dynamic alignment process were determined to be quantifiable via plantar pedobarography. Changes in the angle between the pylon and the socket in the frontal plane produced predictable shifts in foot pressure between medial and lateral foot regions under the prosthesis, and typically shifted pressure to the lateral region of the contralateral foot, regardless of the direction of the modification. Temporal parameters revealed that subjects initially adopt a conservative locomotor pattern after an alignment change but within a few steps begin to refine their gait and approach more symmetrical single limb support times. Plantar pedobarography provides the clinician with potentially useful information to augment dynamic alignment and provides a tangible record of the results of the process.