Clinical-pathologic correlation: The impact of grossing at the bedside.

The unenlightened clinician may submit a skin specimen to the lab and expect an "answer." The experienced clinician knows that in performing skin biopsies, it is critical to select the most appropriate: 1) anatomic location for the biopsy1,2; 2) type of biopsy1,2; 3) depth and breadth of the biopsy; and 4) medium for hematoxylin and eosin staining (formalin) or direct immunofluorescence (Michel's Transport Medium or normal saline).2 Demographic information, anatomic location, clinical context, and differential diagnosis are all critical components of a properly completed requisition form.3-5 Proper biopsy design and appropriate grossing of the tissue at the bedside should be added to this list. In this article, we review the basics of gross pathologic examination and then provide four examples to demonstrate that optimal clinical-pathologic correlation requires the clinician consider the needs of the pathologist when tissue is presented to the lab.

Utilizing technology for diet and exercise change in complex chronic conditions across diverse environments (U-DECIDE): feasibility randomised controlled trial.

BACKGROUND: Diet and exercise are important components of treatment for complex chronic conditions, however access to allied health support is limited. When available, support is often siloed and fragmented. Digital health incorporating patient choice may help to align health care services with preferences and goals. This study evaluated the implementation of a ubiquitously accessible patient-centred digital health diet and exercise service. METHODS: U-DECIDE was a single-centre, 26-week randomised controlled trial set in kidney and liver disease clinics in a tertiary hospital in Brisbane, Australia. Participants were adults with a complex chronic condition referred for dietetic consultation with at least one feature of the metabolic syndrome. All participants received a dietary consultation, an activity monitor and usual care. Intervention participants were offered one text message per week and access to additional digital health options (increased text message frequency, nutrition app, exercise app, group-based diet and/or exercise video consultations). The primary outcome of feasibility was determined by safety (study-related serious adverse events: SRSAEs), recruitment (≥ 50% eligible patients), retention (≥ 70%), exposure uptake (≥ 75% of intervention group had greater access to health professional contact than comparator) and video consultation adherence (≥ 80% attendance). Secondary outcomes included process evaluation metrics and clinical outcomes. RESULTS: Of 67 participants (intervention n = 33, comparator n = 34), 37 (55%) were men, median (IQR) age was 51 (41-58) years. The most chosen digital health options were the nutrition app (n = 29, 88%) and exercise video consultations (n = 26, 79%). Only one participant chose no additional digital health options. The intervention group had no SRSAEs. The study exceeded targets for recruitment (52%), retention (81%) and exposure uptake (94%). Video consultation adherence was 42%. Engagement across digital health options was inconsistent. CONCLUSIONS: Digital health options incorporating patient choice were feasible and can be offered to people with complex chronic disease as a service model option. TRIAL REGISTRATION: Australia and New Zealand Trials Register: Trial Registration Number: ACTRN12620001282976. Registered 27th November 2020.

Comprehensive clinical implementation, workflow, and FMEA of bespoke silicone bolus cast from 3D printed molds using open-source resources.

BACKGROUND: Bolus materials have been used for decades in radiotherapy. Most frequently, these materials are utilized to bring dose closer to the skin surface to cover superficial targets optimally. While cavity filling, such as nasal cavities, is desirable, traditional commercial bolus is lacking, requiring other solutions. Recently, investigators have worked on utilizing 3D printing technology, including commercially available solutions, which can overcome some challenges with traditional bolus. PURPOSE: To utilize failure modes and effects analysis (FMEA) to successfully implement a comprehensive 3D printed bolus solution to replace commercial bolus in our clinic using a series of open-source (or free) software products. METHODS: 3D printed molds for bespoke bolus were created by exporting the DICOM structures of the bolus designed in the treatment planning system and manipulated to create a multipart mold for 3D printing. A silicone (Ecoflex 00-30) mixture is poured into the mold and cured to form the bolus. Molds for sheet bolus of five thicknesses were also created. A comprehensive FMEA was performed to guide workflow adjustments and QA steps. RESULTS: The process map identified 39 and 30 distinct steps for the bespoke and flat sheet bolus workflows, respectively. The corresponding FMEA highlighted 119 and 86 failure modes, with 69 shared between the processes. Misunderstanding of plan intent was a potential cause for most of the highest-scoring failure modes, indicating that physics and dosimetry involvement early in the process is paramount. CONCLUSION: FMEA informed the design and implementation of QA steps to guarantee a safe and high-quality comprehensive implementation of silicone bolus from 3D printed molds. This approach allows for greater adaptability not afforded by traditional bolus, as well as potential dissemination to other clinics due to the open-source nature of the workflow.

Evaluation of knowledge-based planning models for male pelvic CBCT-based online adaptive radiotherapy on conventional linear accelerators.

PURPOSE: To assess the practicality of employing a commercial knowledge-based planning tool (RapidPlan) to generate adapted intact prostate and prostate bed volumetric modulated arc therapy (VMAT) plans on iterative cone-beam computed tomography (iCBCT) datasets. METHODS AND MATERIALS: Intact prostate and prostate bed RapidPlan models were trained utilizing planning data from 50 and 44 clinical cases, respectively. To ensure that refined models were capable of producing adequate clinical plans with a single optimization, models were tested with 50 clinical planning CT datasets by comparing dose-volume histogram (DVH) and plan quality metric (PQM) values between clinical and RapidPlan-generated plans. The RapidPlan tool was then used to retrospectively generate adapted VMAT plans on daily iCBCT images for 20 intact prostate and 15 prostate bed cases. As before, DVH and PQM metrics were utilized to dosimetrically compare scheduled (iCBCT Verify) and adapted (iCBCT RapidPlan) plans. Timing data was collected to further evaluate the feasibility of integrating this approach within an online adaptive radiotherapy workflow. RESULTS: Model testing results confirmed the models were capable of producing VMAT plans within a single optimization that were overall improved upon or dosimetrically comparable to original clinical plans. Direct application of RapidPlan on iCBCT datasets produced satisfactory intact prostate and prostate bed plans with generally improved target volume coverage/conformality and rectal sparing relative to iCBCT Verify plans as indicated by DVH values, though bladder metrics were marginally increased on average. Average PQM values for iCBCT RapidPlans were significantly improved compared to iCBCT Verify plans. The average time required [in mm:ss] to generate adapted plans was 06:09 ± 02:06 (intact) and 07:12 ± 01:04 (bed). CONCLUSION: This study demonstrated the feasibility of leveraging RapidPlan to expeditiously generate adapted VMAT intact prostate and prostate bed plans on iCBCT datasets. In general, adapted plans were dosimetrically improved relative to scheduled plans, emphasizing the practicality of the proposed approach.

Gender differences in outcomes following endoscopic sinus surgery: a systematic review and meta-analysis.

BACKGROUND: The extent to which gender affects outcomes in chronic rhinosinusitis (CRS) is unclear. The objective of this study was to examine differential outcomes between genders following endoscopic sinus surgery (ESS) among CRS patients. METHODS: PubMed/Ovid, Embase and Cochrane databases were queried. Outcomes included disease burden on imaging and endoscopy, patient-reported outcome measures (PROMs) including the Sinonasal Outcome Test (SNOT-22), revision rates, and olfactory outcomes. Meta-analysis was performed using the Mantel-Haenszel method with random effects model. RESULTS: Of 4,656 articles screened, 32 (n=103,499) were included for qualitative analysis and four (n=2,602) for meta-analysis. On qualitative analysis, 19 of the 32 studies noted a significant gender difference in post-operative outcomes, with five studies favoring women and 14 favoring men. Nine of 18 studies with PROMs noted a difference between genders, all favoring men. Olfactory outcomes were mixed with studies divided on favoring men vs women. No studies noted significant gender differences of disease burden on imaging or endoscopy. Across four studies included in the meta-analysis, women had higher preoperative and post-operative SNOT-22 scores. CONCLUSION: Meta-analysis shows that women patients have worse pre and postoperative SNOT-22 scores. Postoperative gender differences are most apparent in studies that examined PROMs. Further research is needed to investigate the underlying causes and to mitigate disparities between genders.

Tetanus prophylaxis in horses: guidelines for New Zealand and Australia based on a critical appraisal of the evidence.

Horses are exquisitely sensitive to tetanus neurotoxin and are exposed to the risk of infection with Clostridium tetani throughout life. The vaccine against tetanus is highly effective at preventing disease, whereas tetanus in unvaccinated populations is associated with high mortality rates. Current guidelines in New Zealand and Australia for the available vaccine contain contradictions and limitations surrounding the optimal tetanus immunisation protocols for both adult horses and foals. This review critically evaluates the scientific literature on tetanus prophylaxis in horses within the context of equine practice and available products in New Zealand and Australia. The review was conducted by a panel of industry and specialist veterinarians to obtain agreement on nine equine tetanus prophylaxis guidelines for practising veterinarians. The primary protocol for tetanus toxoid (TT) immunisation consists of a three-dose series IM for all horses ≥ 6 months of age, and a four-dose series IM is proposed if commencing vaccination in foals between 3 and 6 months of age. Tetanus prophylaxis in foals < 3 months of age relies on passive immunity strategies. Following the completion of the primary protocol, a TT booster dose IM should be administered within 5 years, and every 5 years thereafter. When followed, these protocols should provide adequate protection against tetanus in horses. Additional tetanus prophylaxis guidelines are provided for veterinarians attending a horse experiencing a known "risk event" (e.g. wound, hoof abscess, surgery, umbilical infection). When a correctly vaccinated horse experiences a risk event, pre-existing immunity provides protection against tetanus. When an unvaccinated horse or one with unknown vaccination status, or a foal born to an unvaccinated dam, experiences a risk event, TT IM and tetanus antitoxin (TAT) 1,500 IU SC should be administered simultaneously at separate sites, and the TT primary immunisation protocol should subsequently be completed for the horse's respective age. In previously immunised pregnant broodmares, a TT booster dose administered 4-8 weeks prior to parturition optimises the transfer of passive immunity against tetanus to the newborn foal via colostrum; provided that post-natal IgG concentration in serum is > 800 mg/dL (8 g/L), such foals should be passively protected against tetanus up to 6 months of age. Survivors of clinical tetanus must still receive the primary protocol for vaccination against tetanus. In summary, all horses in New Zealand and Australia should be vaccinated against tetanus with protection maintained throughout life via TT booster doses, facilitated by accurate medical record keeping and client education.

Risk Assessment of Industrial Microbes Using a Terrestrial Mesocosm Platform.

Industrial microbes and bio-derived products have emerged as an integral component of the bioeconomy, with an array of agricultural, bioenergy, and biomedical applications. However, the rapid development of microbial biotechnology raises concerns related to environmental escape of laboratory microbes, detection and tracking thereof, and resultant impact upon native ecosystems. Indeed, though wild-type and genetically modified microbes are actively deployed in industrial bioprocesses, an understanding of microbial interactivity and impact upon the environment is severely lacking. In particular, the persistence and sustained ecosystem impact of industrial microbes following laboratory release or unintentional laboratory escape remains largely unexplored. Herein, we investigate the applicability of soil-sorghum mesocosms for the ecological risk assessment of the industrial microbe, Saccharomyces cerevisiae. We developed and applied a suite of diagnostic and bioinformatic analyses, including digital droplet PCR, microscopy, and phylogenomic analyses to assess the impacts of a terrestrial ecosystem perturbation event over a 30-day time course. The platform enables reproducible, high-sensitivity tracking of S. cerevisiae in a complex soil microbiome and analysis of the impact upon abiotic soil characteristics and soil microbiome population dynamics and diversity. The resultant data indicate that even though S. cerevisiae is relatively short-lived in the soil, a single perturbation event can have sustained impact upon mesocosm soil composition and underlying microbial populations in our system, underscoring the necessity for more comprehensive risk assessment and development of mitigation and biocontainment strategies in industrial bioprocesses.

Client and Clinician Experiences and Perspectives of Exercise Physiology Services During the COVID-19 Pandemic: Qualitative Study.

BACKGROUND: The COVID-19 pandemic led to changes in the delivery of exercise physiology services. The lived experience of those who continued to provide or receive exercise physiology services during the heightened public health restrictions of the inaugural year of the COVID-19 pandemic has received little attention to date. Acquiring this knowledge will be fundamental in addressing whether telehealth is a viable option for service delivery in exercise care, research, and policy. This is especially pertinent in the wake of the COVID-19 pandemic and subsequent global interest in digital health delivery of health care services. OBJECTIVE: This study aims to explore the clinician and client experiences and perspectives of exercise physiology services delivered in person or via telehealth during the inaugural year of the COVID-19 pandemic (after January 25, 2020; the date of the first confirmed case in Australia). METHODS: Eligible participants for this study were adult (aged 18 years or older; capable of understanding and writing in English) clients who received and clinicians who delivered 1 or more exercise physiology sessions in Australia during the first year of the COVID-19 pandemic (June 2020 to June 2021). The data collection period spanned from January 20, 2021, to September 24, 2021. A total of 18 semistructured individual interviews were conducted with accredited exercise physiologists (n=7) and clients (n=11) who engaged with exercise physiology services during this period. All interviews were digitally recorded and transcribed verbatim. Thematic analysis was conducted with themes and subthemes derived using deductive and inductive approaches. RESULTS: A total of 3 dominant themes, each with 2 subthemes, were identified. The first theme was that telehealth enables access to services but limits the use of some clinical tools. Remote access to services was valued by both clinicians and clients, but the exercise clinical environment could not be replicated over telehealth. This was especially true regarding access to exercise equipment. Second, engagement and the "relational space" are limited by telehealth. Perceived challenges regarding social interactions and a sense of community were a limitation for clients, and difficulties fostering clinician-client report were noted by clinicians. Finally, technological challenges are pervasive in the telehealth delivery of exercise services. Both clinicians and clients noted that systems necessary to facilitate telehealth frequently disrupted delivery, and client-based technical issues were influenced by digital health literacy. CONCLUSIONS: Shared client and accredited exercise physiologist experiences highlight key considerations for the ongoing implementation of telehealth to facilitate the uptake and effectiveness of exercise physiology services. These findings imply that the co-design of solutions to client-perceived limitations of telehealth delivery is warranted.

Characterization of imaging performance of a novel helical kVCT for use in image-guided and adaptive radiotherapy.

ClearRT helical kVCT imaging for the Radixact helical tomotherapy system recently received FDA approval and is available for clinical use. The system is intended to enhance image fidelity in radiation therapy treatment planning and delivery compared to the prior MV-based onboard imaging approach. The purpose of this work was to characterize the imaging performance of this system and compare this performance with that of clinical systems used in image-guided and/or adaptive radiotherapy (ART) or computed tomography (CT) simulation, including Radixact MVCT, TomoTherapy MVCT, Varian TrueBeam kV OBI CBCT, and the Siemens SOMATOM Definition Edge kVCT. A CT image quality phantom was scanned across clinically relevant acquisition modes for each system to evaluate image quality metrics, including noise, uniformity, contrast, spatial resolution, and CT number linearity. Similar noise levels were observed for ClearRT and Siemens Edge, whereas noise for the other systems was ∼1.5-5 times higher. Uniformity was best for Siemens Edge, whereas most scans for ClearRT exhibited a slight "cupping" or "capping" artifact. The ClearRT and Siemens Edge performed best for contrast metrics, which included low-contrast visibility and contrast-to-noise ratio evaluations. Spatial resolution was best for TrueBeam and Siemens Edge, whereas the three kVCT systems exhibited similar CT number linearity. Overall, these results provide an initial indication that ClearRT image quality is adequate for image guidance in radiotherapy and sufficient for delineating anatomic structures, thus enabling its use for ART. ClearRT also showed significant improvement over MVCT, which was previously the only onboard imaging modality available on Radixact. Although the acquisition of these scans does come at the cost of additional patient dose, reported CTDI values indicate a similar or generally reduced machine output for ClearRT compared to the other systems while maintaining comparable or improved image quality overall.

A designated trauma social worker improves coordination of patient care by coordinating ancillary consults.

Trauma patients face unique challenges that require coordination by social workers knowledgeable in the intricacies of trauma patient psychosocial support which is often achieved by obtaining ancillary consultations. The impact of employing a designated trauma social worker (DTSW) in the utilization of these consults has not been described. A retrospective review was conducted of trauma patients admitted to an academic, urban Level 1 trauma center. The pre-intervention cohort (n = 272) corresponded to patients admitted before the presence of a DTSW (01/2013 to 06/2013), while the post-intervention cohort (n = 282) corresponded to patients admitted afterward (09/2015 to 01/2016). Data collection included demographics, injury profile, and types of interdisciplinary or therapy consultations. Post-intervention patients were found to be older and admitted with more injuries. Supportive care, physical therapy and occupational therapy consultations were more likely to be obtained in the post-intervention cohort. Hospital length of stay remained unchanged. This study suggests that the implementation of a DTSW significantly facilitates the utilization of interdisciplinary consultations. Length of stay remains unchanged, suggesting that a DTSW helps to coordinate care in a timely manner without increasing the hospital stay. DTSW implementation may be considered in trauma centers where one does not currently exist.

Comparative computer-assisted sperm analysis in non-human primates.

BACKGROUND: Biomedical research has recently focused on developing new models of human disease by implementing genome-editing strategies in non-human primates (NHPs) to introduce relevant gene mutations. There is a need to establish objective semen evaluation methods to select sires for in vitro fertilization to perform germline editing in embryos. METHODS: Sperm motility kinematic parameters were evaluated using a computer-assisted semen analysis (CASA) instrument for rhesus macaques (Macaca mulatta), cynomolgus macaques (Macaca fascicularis), and common marmosets (Callithrix jacchus). RESULTS: Normative sperm kinematic parameters were established, revealing differences between marmosets and macaques. The impact of season on rhesus macaque sperm motility was modest, where changes in sperm motility related to season were dependent on the individual male. CONCLUSIONS: These data provide a baseline of normative kinematic parameters for three captive NHP species, in which implementation of CASA may serve as a tool to evaluate NHP semen quality.

First report of pulmonary disease associated with Nicoletella semolina in a horse in New Zealand.

Case history: A 9-year-old warmblood gelding with a history of chronic intermittent tachypnoea and dyspnoea was presented for evaluation and removal of a mass on the left side of the neck. A fibrous mass adherent to the left jugular vein developed and was removed surgically 6 weeks later, at which time the owner requested an evaluation of the cause of the persistent respiratory signs first noted on primary admission. Clinical findings and treatment: Clinical findings included coarse lung sounds on thoracic auscultation, tracheal wheeze, and an abnormal trans-tracheal aspirate. These findings, in addition to the results of ultrasonographic imaging of the thorax and transtracheal cytology, were suggestive of bacterial bronchopneumonia. Initial antimicrobial therapy included I/M 22 mg/kg procaine penicillin every 12 hours and I/V 6.6 mg/kg gentamicin sulphate every 24 hours. The horse's clinical signs improved within 36 hours. It was discharged after 6 days, and at the owner's request antimicrobial therapy was changed to 25 mg/kg trimethoprim/sulphadimidine to be given orally every 12 hours for 10 days. One month later, the horse had recovered and there were no further complications reported by the owner except for an occasional cough while grazing Laboratory findings: Bacterial culture of transtracheal wash fluid resulted in the isolation of Nicoletella semolina as the sole organism, later confirmed by genotyping. Attempts to subculture the organism for antimicrobial susceptibility testing were unsuccessful. Diagnosis: Infectious bronchopneumonia associated with Nicoletella semolina Clinical relevance: Further work is required to determine whether N. semolina is acting as an opportunistic commensal of the equine respiratory tract or a primary pathogen. However, this article reports the first instance in New Zealand of an association between the presence of this organism and respiratory disease in a horse.

Isolates, antimicrobial susceptibility profiles and multidrug resistance of bacteria cultured from samples collected from sheep in New Zealand (2003-2016).

Aim: To describe the common species, antimicrobial susceptibility and multidrug resistance (MDR) of bacteria cultured from samples submitted to veterinary diagnostic laboratories from sheep in New Zealand between 2003 and 2016. Methods: Bacterial culture and antimicrobial susceptibility test data from June 2003 to March 2016 for animals identified as sheep were obtained from two commercial veterinary diagnostic laboratories in New Zealand. Submission information included animal signalment, geographic origin, specimen description, the organisms cultured, and where available, antimicrobial susceptibilities of the isolates. MDR was defined as any isolate with resistance to ≥3 antimicrobial classes. Results: There were 1,971 unique laboratory submissions, yielding 2,188 isolates. Of the 1,971 submissions, the most commonly represented breeds were Romney (933; 47.3%), Romney cross (264; 13.4%), and Coopworth (197; 10.0%), and there were more submissions from females (1,006; 51.0%) than males (184; 9.3%). Most submissions were from Canterbury (549; 27.9%), Southland (471; 23.9%), and Manawatu-Wanganui (272; 13.8%) regions. Other signalment data were inconsistently described. Submitted samples most commonly originated from the gastrointestinal tract (852; 43.2%), faeces (378; 12.1%), or liver (146; 7.4%). Of the 2,188 isolates, 1,771 (80.9%) were identified by species and 247 (11.4%) by genus, with the most common isolates being Salmonella spp. (880; 40.2%), Campylobacter spp. (408; 18.6%), Listeria spp. (140; 6.4%) and Yersinia spp. (113; 5.2%). Susceptibility results were available for 117/2,188 (5.3%) isolates from 51/1,971 (2.6%) submissions. No antimicrobial susceptibility data were available for Salmonella spp., Campylobacter spp., Listeria spp. or Yersinia spp. Overall for the isolates tested, susceptibility to the fluoroquinolones and tetracyclines was greatest, and MDR was found in 24/117 (20.5%) isolates. MDR was a more frequent finding for Enterococcus spp., Bacillus spp., and Proteus mirabilis, but was infrequent in isolates of Staphylococcus aureus, alpha-haemolytic streptococci, Escherichia coli or Enterobacter spp. Conclusions and clinical relevance: This is the first report on antimicrobial susceptibility and MDR for isolates from laboratory submissions from sheep in New Zealand. The low numbers of isolates submitted for antimicrobial susceptibility testing during the period studied mean that these findings provide limited insights into antimicrobial resistance in this population, and highlight the need to address significant gaps in our understanding of why veterinarians do not more frequently submit samples from sheep for bacterial culture and susceptibility testing. Abbreviation: AMR: Antimicrobial resistance; MDR: Multidrug resistance.

Zika virus in rhesus macaque semen and reproductive tract tissues: a pilot study of acute infection†.

Although sexual transmission of Zika virus (ZIKV) is well-documented, the viral reservoir(s) in the male reproductive tract remains uncertain in humans and immune-intact animal models. We evaluated the presence of ZIKV in a rhesus macaque pilot study to determine persistence in semen, assess the impact of infection on sperm functional characteristics, and define the viral reservoir in the male reproductive tract. Five adult male rhesus monkeys were inoculated with 105 PFU of Asian-lineage ZIKV isolate PRVABC59, and two males were inoculated with the same dose of African-lineage ZIKV DAKAR41524. Viremia and viral RNA (vRNA) shedding in semen were monitored, and a cohort of animals were necropsied for tissue collection to assess tissue vRNA burden and histopathology. All animals exhibited viremia for limited periods (1-11 days); duration of shedding did not differ significantly between viral isolates. There were sporadic low levels of vRNA in the semen from some, but not all animals. Viral RNA levels in reproductive tract tissues were also modest and present in the epididymis in three of five cases, one case in the vas deferens, but not detected in testis, seminal vesicles or prostate. ZIKV infection did not impact semen motility parameters as assessed by computer-assisted sperm analysis. Despite some evidence of prolonged ZIKV RNA shedding in human semen and high tropism of ZIKV for male reproductive tract tissues in mice deficient in Type 1 interferon signaling, in the rhesus macaques assessed in this pilot study, we did not consistently find ZIKV RNA in the male reproductive tract.

Infrared spectroscopy of serum as a potential diagnostic screening approach for naturally occurring canine osteoarthritis associated with cranial cruciate ligament rupture.

OBJECTIVE: To evaluate infrared (IR) spectroscopy of serum as a screening tool to differentiate dogs affected by naturally occurring osteoarthritis (OA) associated with cranial cruciate ligament rupture (CrCLR) and controls. METHOD: 104 adult dogs with CrCLR (affected group) and 50 adult control dogs were recruited for this prospective observational study. Serum samples were collected preoperatively from CrCLR dogs and from a subset of these dogs at 4-, and 12-week post-surgical intervention to stabilize the affected stifles. Serum was collected once from control dogs. Dry films were made from serum samples, and IR absorbance spectra acquired. Data preprocessing, principal component analysis and multivariate analysis of covariance were performed to separate samples from the two groups, and to evaluate temporal differences. Weighted logistic regression with L1 regularization method was used to develop a predictive model. Model performance based on an independent test set was evaluated. RESULTS: Spectral data analysis revealed significant separation between the sera of CrCLR and control dogs (P < 0.0001), but not amongst different time points in the OA group. The sensitivity, specificity, AUC and accuracy of the test set were 84.62%, 96.15%, 93.20% and 92.31% respectively. CONCLUSIONS: These findings confirm the potential of IR-spectroscopy of serum with chemometrics methods to differentiate controls from dogs with OA associated with CrCLR. This is the first step in development of an economic, and comparatively simple IR-based screening serum test for OA. Utility of this tool as a clinical screening and diagnostic test requires further investigation and validation.

Metabolic repair through emergence of new pathways in Escherichia coli.

Escherichia coli can derive all essential metabolites and cofactors through a highly evolved metabolic system. Damage of pathways may affect cell growth and physiology, but the strategies by which damaged metabolic pathways can be circumvented remain intriguing. Here, we use a ΔpanD (encoding for aspartate 1-decarboxylase) strain of E. coli that is unable to produce the ß-alanine required for CoA biosynthesis to demonstrate that metabolic systems can overcome pathway damage by extensively rerouting metabolic pathways and modifying existing enzymes for unnatural functions. Using directed cell evolution, rewiring and repurposing of uracil metabolism allowed formation of an alternative ß-alanine biosynthetic pathway. After this pathway was deleted, a second was evolved that used a gain-of-function mutation on ornithine decarboxylase (SpeC) to alter reaction and substrate specificity toward an oxidative decarboxylation-deamination reaction. After deletion of both pathways, yet another independent pathway emerged using polyamine biosynthesis, demonstrating the vast capacity of metabolic repair.

Opinions of Speech-Language Pathologists Regarding Speech Management for Children With Cleft Lip and Palate.

OBJECTIVE: The purpose of the present study was to examine practice patterns and opinions that speech-language pathologists (SLPs) have about speech-language intervention for children with cleft lip and palate. METHODS: One hundred seven speech-language pathology members of the American Speech-Language-Hearing Association Special Interest Group 5: Craniofacial and Velopharyngeal Disorders Special Interest Group completed a 37-item online survey that examined common practices in early intervention as well as opinions about speech characteristics, assessment, and management strategies for children with cleft lip and palate. RESULTS: The overwhelming majority of respondents (96%) agreed that speech-language pathologists (SLPs) should meet with parents before palatal surgery to discuss speech-language issues. Although 90% of the SLPs identified increasing consonant inventory as an early intervention goal, lack of consensus was evident regarding the type of consonant to stimulate. Respondents agreed that while blowing activities are not useful in strengthening labial, lingual, or velopharyngeal movements, they are useful in heightening awareness of oral airflow for children with cleft palate. A large degree of variability was evident in opinions regarding prevalence and treatment of compensatory articulations as well as the effectiveness of treatment strategies designed to reduce perceived hypernasality and audible nasal emission. CONCLUSIONS: The findings of this study indicate a large degree of variability in opinions of SLP respondents regarding assessment and treatment of children with cleft lip and palate.

A pilot study to investigate the measurement of immunoglobulin A in Welsh Cob and Welsh Pony foals' faeces and their dam's milk.

Aims: To determine if an ELISA for measurement of IgA in equine serum could be used to measure concentrations of IgA in foal faeces and to determine correlations with concentrations in the milk of the dam.Methods: Faeces from 20 Welsh Cob and Welsh Pony foals and milk from their dams were collected within 12 hours (Day 0) and at 6 days after parturition (Day 6). On Day 6, faeces could not be collected from 2/20 foals, and milk samples could not be collected from 3/20 mares. An equine IgA ELISA validated for serum and plasma was used to measure concentrations of IgA in all samples in triplicate. The precision of the assay for each sample type was determined using modified CV.Results: IgA was not detectable in 7/20 Day 0 faecal samples and in 2/18 Day 6 faecal samples. For samples with detectable IgA, the mean modified CV was 10.5 (95% CI = 6.0-15.0)% for Day 0 faecal samples, and was 6.8 (95% CI = 4.3-9.4)% for Day 6 faecal samples. Median concentrations of IgA in faeces on Day 0 were lower than concentrations on Day 6 (0.7 mg/g vs. 37 mg/g dry matter; p = 0.003). Concentrations of IgA in milk and faeces on Day 6 were statistically correlated (r = 0.59; p = 0.006).Conclusions and clinical relevance: The IgA ELISA showed acceptable precision when used to estimate concentrations of IgA in foal faeces during the first week of life, but IgA could not be detected in 37% of meconium samples collected on Day 0. This assay may be useful for investigation of the role of maternal milk IgA in the gastrointestinal tract of neonatal foals, but further assessment of both accuracy and precision of the ELISA is required.