18F-Flotufolastat Positron Emission Tomography in African American Patients With Suspected Prostate Cancer Recurrence: Findings From the Phase 3 SPOTLIGHT Study.

Purpose: Although African American (AA) patients are disproportionately affected by prostate cancer, they are often underrepresented in oncology clinical trials. The SPOTLIGHT study (NCT04186845) assessed the novel diagnostic positron emission tomography radiopharmaceutical, 18F-flotufolastat (18F-rhPSMA-7.3), in patients with recurrent prostate cancer. The proportion of AA patients enrolled in SPOTLIGHT (17%) was greater than typically enrolled in oncology trials (8.5%) and was representative of the US population (14%). This post hoc analysis of SPOTLIGHT evaluates the diagnostic performance of 18F-flotufolastat in AA patients. Methods and Materials: Patients underwent positron emission tomography/computed tomography 50 to 70 minutes after intravenous administration of 296 MBq 18F-flotufolastat. Three blinded readers evaluated all images, with the majority read (agreement of ≥2 readers) result reported here. Standard of truth (SoT) was established with histopathology or correlative imaging. Data from AA patients were evaluated to determine the 18F-flotufolastat overall detection rate (DR), positive predictive value (PPV), and verified DR (VDR). VDR (SoT-verified) is equivalent to DR × PPV. Results: In total, 61 of 366 (17%) patients were AAs. Although baseline characteristics were broadly similar, fewer AA patients (56%) had undergone prostatectomy than non-AA patients (82%). The patient-level DR was 93% (57/61) in AA patients, increasing from 67% at prostate-specific antigen <0.5 ng/mL to 100% at prostate-specific antigen ≥10 ng/mL. Patient-level DR was marginally lower in all other patients (87%, 264/305). However, when stratifying by prior treatment, DRs were similar across ethnic groups in postprostatectomy patients, but in patients with intact prostates, AA patients had higher prostate DR than non-AA patients. SoT-verification (predominantly with conventional imaging [79%]) gave a VDR of 64% and PPV of 68% in AA patients, versus 55% and 64%, respectively, in all other patients. Conclusions: 18F-Flotufolastat DRs were marginally higher in AA patients than in all other patients enrolled in SPOTLIGHT. High VDR and PPV were also achieved in AA patients from across all participating centers, indicating the broad applicability of newly US Food and Drug Administration-approved 18F-flotufolastat to the US population as a whole.

Impact of Clinical Factors on 18F-Flotufolastat Detection Rates in Men With Recurrent Prostate Cancer: Exploratory Analysis of the Phase 3 SPOTLIGHT Study.

Purpose: 18F-Flotufolastat (18F-rhPSMA-7.3) is a newly approved prostate-specific membrane antigen targeting radiopharmaceutical for diagnostic imaging of prostate cancer (PCa). SPOTLIGHT (National Clinical Trials 04186845) evaluated 18F-flotufolastat in men with suspected PCa recurrence. Here, we present results of predefined exploratory endpoints from SPOTLIGHT to evaluate the impact of clinical factors on 18F-flotufolastat detection rates (DR). Methods and Materials: The impact of baseline prostate-specific antigen (PSA), PSA doubling time (PSAdt), and International Society of Urologic Pathology Grade Group (GG) on 18F-flotufolastat DR was evaluated among all SPOTLIGHT patients with an evaluable scan, with DR stratified according to the patients' prior treatment (radical prostatectomy ± radiation therapy [RP] or radiation therapy only [RT]). The patients underwent positron emission tomography 50 to 70 minutes after receiving 18F-flotufolastat (296 MBq IV), and scans were read by 3 blinded central readers, with the majority read representing agreement between ≥2 readers. Results: In total, 389 men (median PSA: 1.10 ng/mL) were evaluable. By majority read, 18F-flotufolastat identified distant lesions in 39% and 43% of patients treated with prior RP or RT, respectively. The overall DR broadly increased with increasing PSA (<0.2 ng/mL: 33%; ≥10 ng/mL: 100%). Among patients with PSA <1 ng/mL, 68% had positive scans, and 27% had extrapelvic findings. PSAdt was available for 145/389 (37%) patients. PSAdt did not appear to influence 18F-flotufolastat DR (77%-90% across all PSAdt categories). Among patients with prior RP, DR ranged from 70% to 83% across PSAdt categories, and 100% DR was reported for all post-RT patients. In total, 362/389 (93%) patients had baseline GG data. Overall DRs were uniformly high (75%‒95%) across all GG. When stratified by prior treatment, DRs across all GG were 69% to 89% in patients with prior RP and ≥96% in patients with prior RT. Conclusions: 18F-Flotufolastat-positron emission tomography enabled the accurate detection of recurrent PCa lesions across a wide range of PSA, PSAdt, and International Society of Urologic Pathology GG, thus supporting its clinical utility for a broad range of patients with recurrent PCa.

Global prevalence of musculoskeletal pain in rural and urban populations. A systematic review with meta-analysis. Musculoskeletal pain in rural and urban populations.

INTRODUCTION: To systematically compare the global prevalence of musculoskeletal pain and care-seeking in rural and urban populations. METHODS: A systematic review with meta-analysis of observational studies reporting a direct comparison of rural and urban populations was conducted worldwide and included back, knee, hip, shoulder, neck pain and a broad diagnosis of 'musculoskeletal pain'. A search strategy combining terms related to 'prevalence', 'musculoskeletal pain' and 'rural' was used on the following databases: MEDLINE, Embase, CINAHL, Scopus, and rural and remote health from their inception to 1 June 2022. Random-effects meta-analysis was used to pool the data. Results were presented as odds ratios (OR) along with 95% confidence intervals (95% CI). RESULTS: A total of 42 studies from 24 countries were included with a total population of 489 439 participants. The quality scores for the included studies, using the modified Newcastle Ottawa Scale tool, showed an average score of 0.78/1, which represents an overall good quality. The pooled analysis showed statistically greater odds of hip (OR = 1.62, 95% CI = 1.23-2.15), shoulder (OR = 1.42, 95% CI = 1.06-1.90) and overall musculoskeletal pain (OR = 1.26, 95% CI = 1.08-1.47) in rural populations compared to urban populations. Although the odds of seeking treatment were higher in rural populations this relationship was not statistically significant (OR = 0.76, 95% CI = 0.55-1.03). CONCLUSION: Very low-certainty evidence suggests that musculoskeletal, hip and shoulder pain are more prevalent in rural than urban areas, although neck, back and knee pain, along with care-seeking, showed no significant difference between these populations. Strategies aimed to reduce the burden of musculoskeletal pain should consider the specific needs and limited access to quality evidence-based care for musculoskeletal pain of rural populations.

Outcomes and Performance Following Posteromedial Elbow Debridement in Major League Baseball Players.

BACKGROUND: Overhead athletes are particularly susceptible to elbow valgus extension overload syndrome and development of pathologic changes in the posteromedial elbow. Though arthroscopic débridement/osteophyte resection is frequently performed, few studies have analyzed the outcomes of this procedure, and none have specifically addressed professional level athletes. HYPOTHESIS/PURPOSE: We hypothesized that following posteromedial elbow débridement, Major League Baseball (MLB) pitchers would exhibit a higher rate of ulnar collateral ligament (UCL) reconstruction than baseline incidence in the existing literature, along with a decline in pitching performance. METHODS: Using publicly accessible websites, MLB athletes undergoing posteromedial elbow débridement from 2007 to 2022 were identified. Demographic information, procedure details, return to play (RTP) information, return to the disabled/injured list (DL/IL), subsequent UCL reconstruction, and pitching statistics were analyzed. Pitching performance metrics included Earned Runs Average (ERA), Walks Plus Hits Per Innings Pitched (WHIP), innings pitched, and fastball velocity. RESULTS: A total of 39 MLB players, including 26 pitchers, were included. Within the first three seasons after surgery, 82.1% (n=32) of players returned to play at the MLB level at a mean time of 176.1 ± 69 days. Pitchers exhibited a return to play (RTP) rate of 76.9% (n=20) at 175.8 ± 16 days. A total of 38.5% (n=10) of pitchers returned to the DL/IL for elbow-related issues within three seasons. Subsequent UCL reconstruction was seen only in pitchers, with a frequency of 19.2% (n=5). No statistically significant differences between single season pre/postoperative pitching metrics were identified. A small but significant (p<0.05) decrease in fastball velocity (94.4 vs 92.84; p=0.02) was observed over a three-season comparison. CONCLUSION: Contrary to our hypothesis, this study demonstrates that posteromedial elbow débridement is a viable surgery in MLB athletes, with RTP rate of 82.1% and no increase in rate of UCL reconstruction. Furthermore, there was no significant difference in single season pre- and postoperative statistical pitching performance. However, over three years postoperatively, there was a 38.5% rate of return to the DL/IL for ongoing elbow ailment and a significant decrease in pitch velocity, raising some concern over the longevity of postoperative improvements.

Interreader and Intrareader Reproducibility of 18F-Flotufolastat Image Interpretation in Patients with Newly Diagnosed or Recurrent Prostate Cancer: Data from Two Phase 3 Prospective Multicenter Studies.

Interreader and intrareader reproducibility of 18F-flotufolastat PET/CT scans in newly diagnosed and recurrent prostate cancer patients was assessed from masked image evaluations from two phase 3 studies. Methods: 18F-flotufolastat PET/CT images of newly diagnosed (n = 352) or recurrent (n = 389) patients were evaluated by 3 masked readers. Cohen κ was used to assess pairwise patient- and region-level interreader agreement. Agreement among all readers was assessed using Fleiss κ. Intrareader agreement between the first and repeat read (20% of images, ≥4 wk later) was assessed using Cohen κ. Results: Pairwise interreader agreement was 95% or better (newly diagnosed) and 75% or better (recurrent). The κ coefficients were impacted by the high-agreement-low-κ paradox: Cohen κ ranged from not estimable to 0.55, whereas Fleiss κ was 0.50 (newly diagnosed) and 0.41 (recurrent). Agreement was highest in the prostate of newly diagnosed patients (≥95%) and in the pelvic lymph nodes in recurrent patients (≥87%). Intrareader agreement was 86% or better across both populations. Conclusion: 18F-flotufolastat PET/CT images can be reliably interpreted, with a high degree of inter- and intrareader agreement.

True-Positive 18F-Flotufolastat Lesions in Patients with Prostate Cancer Recurrence with Baseline-Negative Conventional Imaging: Results from the Prospective, Phase 3, Multicenter SPOTLIGHT Study.

18F-rhPSMA-7.3 (18F-flotufolastat) is a high-affinity prostate-specific membrane antigen-targeted diagnostic radiopharmaceutical for PET imaging in patients with prostate cancer. Here, we report findings from the SPOTLIGHT study (NCT04186845), assessing the performance of 18F-flotufolastat PET/CT for identifying prostate-specific membrane antigen-positive lesions confirmed by standard of truth (SoT) in men with biochemical recurrence of prostate cancer and negative conventional imaging at baseline. Methods: Men with biochemical recurrence received 296 MBq of 18F-flotufolastat intravenously and then underwent PET/CT 50-70 min later. 18F-flotufolastat PET/CT findings were evaluated by 3 masked central readers and verified using histopathology or follow-up confirmatory imaging (CT, MRI, bone scan, or 18F-fluciclovine PET/CT) as the SoT. The present analysis evaluated all patients who had negative conventional imaging at baseline, underwent 18F-flotufolastat PET/CT, and had SoT verification by histopathology or follow-up confirmatory imaging to report detection rate (DR), which is the number of patients with at least 1 PET-positive lesion, divided by the number of evaluable patients, and verified DR (VDR), which is the proportion of patients with at least 1 true-positive lesion as verified by SoT, of all patients scanned (PET-positive and PET-negative scans). DR and VDR were calculated and stratified according to prior therapy. Majority read data (agreement between ≥2 readers) are reported. Results: In total, 171 patients with negative baseline conventional imaging and SoT by histopathology or post-PET confirmatory imaging were evaluated. By majority read, the overall 18F-flotufolastat DR among these patients was 95% (163/171; 95% CI, 91.0%-98.0%), and 110 of 171 of these patients had at least 1 true-positive lesion identified (VDR, 64%; 95% CI, 56.7%-71.5%). In the postprostatectomy group (133/171), 8.3% of patients had at least 1 true-positive lesion in the prostate bed, 28% in pelvic lymph nodes, and 35% in other sites. Among those who had received radiotherapy (36/171), 50% of patients had true-positive detections in the prostate, 8.3% in pelvic lymph nodes, and 36% in other sites. Conclusion: 18F-flotufolastat frequently identified true-positive prostate cancer lesions in patients with negative conventional imaging. 18F-flotufolastat may help to better define sites of disease recurrence and inform salvage therapy decisions than does conventional imaging, potentially leading to improved outcomes.

Diagnostic Performance and Safety of Positron Emission Tomography with 18F-rhPSMA-7.3 in Patients with Newly Diagnosed Unfavourable Intermediate- to Very-high-risk Prostate Cancer: Results from a Phase 3, Prospective, Multicentre Study (LIGHTHOUSE).

BACKGROUND: Radiohybrid (rh) 18F-rhPSMA-7.3 is a novel high-affinity prostate-specific membrane antigen (PSMA)-targeting radiopharmaceutical for prostate cancer (PCa) imaging. OBJECTIVE: To evaluate the diagnostic performance and safety of 18F-rhPSMA-7.3 in newly diagnosed PCa patients planned for prostatectomy. DESIGN, SETTING, AND PARTICIPANTS: Data on 18F-rhPSMA-7.3 were reported from the phase 3 prospective, multicentre LIGHTHOUSE study (NCT04186819). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Patients underwent positron emission tomography/computed tomography (PET/CT) 50-70 min after an injection of 296 MBq 18F-rhPSMA-7.3. Images were interpreted locally and by three blinded independent readers. The coprimary endpoints were patient-level sensitivity and specificity for the detection of pelvic lymph node (PLN) metastases, validated using histopathology at PLN dissection. Prespecified statistical thresholds (lower bounds of 95% confidence interval [CI]) were set at 22.5% for sensitivity and 82.5% for specificity. RESULTS AND LIMITATIONS: Of 372 patients screened, 352 had evaluable 18F-rhPSMA-7.3-PET/CT and 296 (99 [33%] with unfavourable intermediate-risk [UIR] and 197 [67%] with high-/very-high-risk [VHR] PCa) subsequently underwent surgery. As per the independent reads, 23-37 (7.8-13%) patients had 18F-rhPSMA-7.3-positive PLN. Seventy (24%) patients had one or more positive PLNs on histopathology. The sensitivity for PLN detection was 30% (95% CI, 19.6-42.1%) for reader 1, 27% (95% CI, 17.2-39.1%) for reader 2, and 23% (95% CI, 13.7-34.4%) for reader 3, not meeting the prespecified threshold. Specificity was 93% (95% CI, 88.8-95.9%), 94% (95% CI, 89.8-96.6%), and 97% (95% CI, 93.7-98.7%), respectively, exceeding the threshold for all readers. Specificity was high (≥92%) across both risk stratifications. Sensitivity was higher among high-risk/VHR (24-33%) than among UIR (16-21%) patients. Extrapelvic (M1) lesions were reported for 56-98/352 (16-28%) patients who underwent 18F-rhPSMA-7.3-PET/CT irrespective of surgery. Verification of these (predominantly by conventional imaging) gave a verified detection rate of 9.9-14% (positive predictive value, 51-63%). No serious adverse events were observed. CONCLUSIONS: Across all risk stratifications, 18F-rhPSMA-7.3-PET/CT had high specificity, meeting the specificity endpoint. The sensitivity endpoint was not met, although higher sensitivity was noted among high-risk/VHR than among UIR patients. Overall, 18F-rhPSMA-7.3-PET/CT was well tolerated, and identified N1 and M1 disease prior to surgery in newly diagnosed PCa patients. PATIENT SUMMARY: In order to select the most appropriate treatment for patients with prostate cancer, it is critical to diagnose the disease burden accurately at initial diagnosis. In this study, we investigated a new diagnostic imaging agent in a large population of men with primary prostate cancer. We found it to have an excellent safety profile and to provide clinically useful information regarding the presence of disease beyond the prostate.

Diagnostic Performance and Safety of 18F-rhPSMA-7.3 Positron Emission Tomography in Men With Suspected Prostate Cancer Recurrence: Results From a Phase 3, Prospective, Multicenter Study (SPOTLIGHT).

PURPOSE: SPOTLIGHT (NCT04186845) evaluated diagnostic performance and safety of radiohybrid 18F-rhPSMA-7.3, a novel high-affinity positron emission tomography radiopharmaceutical. MATERIALS AND METHODS: Men with prostate cancer recurrence underwent positron emission tomography/CT 50-70 minutes after intravenous administration of 296±20% MBq 18F-rhPSMA-7.3. To assess the coprimary end points (verified detection rate and combined region-level positive predictive value), 3 blinded, independent central readers evaluated the scans. Verified detection rate is equivalent to the overall detection rate × positive predictive value. Standard of truth was established for each patient using histopathology or confirmatory imaging. Statistical thresholds (lower bounds of the confidence intervals) of 36.5% and 62.5% were prespecified for verified detection rate and combined region-level positive predictive value, respectively. Additional end points included detection rate, verified detection rate, and combined region-level positive predictive value in patients with histopathology standard of truth, and safety. RESULTS: The overall 18F-rhPSMA-7.3 detection rate among all 389 patients with an evaluable scan was 83% (majority read). Among the 366 patients (median prostate-specific antigen 1.27 ng/mL) for whom a standard of truth (histopathology [n=69]/confirmatory imaging only [n=297]) was available, verified detection rate ranged from 51% (95% CI 46.1-56.6) to 54% (95% CI 48.8-59.3), exceeding the prespecified statistical threshold. Combined region-level positive predictive value ranged from 46% (95% CI 42.0-50.3) to 60% (95% CI 55.1-65.5) across the readers, not meeting the threshold. In the subset of patients with histopathology standard of truth, the verified detection rate and combined region-level positive predictive value were both above the prespecified thresholds (majority read, 81% [95% CI 69.9-89.6] and 72% [95% CI 62.5-80.7], respectively). No significant safety concerns were identified. CONCLUSIONS: 18F-rhPSMA-7.3 offers a clinically meaningful verified detection rate for localization of recurrent prostate cancer. Despite missing the coprimary end point of combined region-level positive predictive value, the totality of the data support the potential clinical utility of 18F-rhPSMA-7.3.

Animal alphacoronaviruses found in human patients with acute respiratory illness in different countries.

Here we review the existing evidence of animal alphacoronaviruses (Alphacoronavirus 1 species) circulating in human patients with acute respiratory illness. Thus far, the viruses similar to canine, feline and porcine alphacoronaviruses (including the most recent CCoV-HuPn-2018 and HuCCoV_Z19) have been detected in humans in Haiti, Malaysia, Thailand, and USA. The available data suggest that these viruses emerged in different geographic locations independently and have circulated in humans for at least 20 years. Additional studies are needed to investigate their prevalence and disease impact.

RETRACTED ARTICLE: The 'rhetorical concession': a linguistic analysis of debates and arguments in mental health.

We, the editors and publisher of Journal of Mental Health, have retracted the following article: Garner, B., Kinderman, P., & Davis, P. (2021). 'The "rhetorical concession": a linguistic analysis of debates and arguments in mental health', DOI: 10.1080/09638237.2021.2022631Since publication, a conflict of interest has been brought to our attention. Blog 'F', which is one of a series of blogs analysed in this paper, has been identified as the blog of Peter Kinderman, co-author of the paper. This conflict of interest was not disclosed upon submission of the article, and we consequently believe that this compromises the reliability of the reviews and the paper's findings. We are therefore retracting the article.Our decision has been informed by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as 'Retracted'. .

Development, testing and validation of a SARS-CoV-2 multiplex panel for detection of the five major variants of concern on a portable PCR platform.

Many SARS-CoV-2 variants have emerged during the course of the COVID-19 pandemic. These variants have acquired mutations conferring phenotypes such as increased transmissibility or virulence, or causing diagnostic, therapeutic, or immune escape. Detection of Alpha and the majority of Omicron sublineages by PCR relied on the so-called S gene target failure due to the deletion of six nucleotides coding for amino acids 69-70 in the spike (S) protein. Detection of hallmark mutations in other variants present in samples relied on whole genome sequencing. However, whole genome sequencing as a diagnostic tool is still in its infancy due to geographic inequities in sequencing capabilities, higher cost compared to other molecular assays, longer turnaround time from sample to result, and technical challenges associated with producing complete genome sequences from samples that have low viral load and/or high background. Hence, there is a need for rapid genotyping assays. In order to rapidly generate information on the presence of a variant in a given sample, we have created a panel of four triplex RT-qPCR assays targeting 12 mutations to detect and differentiate all five variants of concern: Alpha, Beta, Gamma, Delta, and Omicron. We also developed an expanded pentaplex assay that can reliably distinguish among the major sublineages (BA.1-BA.5) of Omicron. In silico, analytical and clinical testing of the variant panel indicate that the assays exhibit high sensitivity and specificity. This panel can help fulfill the need for rapid identification of variants in samples, leading to quick decision making with respect to public health measures, as well as treatment options for individuals. Compared to sequencing, these genotyping PCR assays allow much faster turn-around time from sample to results-just a couple hours instead of days or weeks.

EHealth to empower patients with musculoskeletal pain in rural Australia (EMPoweR) a randomised clinical trial: study protocol.

BACKGROUND: Low back pain (LBP) and knee osteoarthritis (OA) are major contributors to disability worldwide. These conditions result in a significant burden at both individual and societal levels. Engagement in regular physical activity and exercise programs are known to improve physical function in both chronic LBP and knee OA populations. For people residing in rural areas, musculoskeletal conditions are often more frequent and disabling compared to urban populations, which could be the result of reduced access to appropriate health services and resources in rural settings. EHealth is an innovative solution to help provide equitable access to treatment for people with musculoskeletal pain living in rural settings. METHODS/DESIGN: We will conduct a randomised clinical trial investigating the effects of an eHealth intervention compared to usual care, for people with chronic non-specific LBP or knee OA in rural Australia. We will recruit 156 participants with non-specific chronic LBP or knee OA. Following the completion of baseline questionnaires, participants will be randomly allocated to either the eHealth intervention group, involving a tailored physical activity and progressive resistance exercise program remotely delivered by a physiotherapist (n = 78), or usual care (n = 78) involving referral to a range of care practices in the community. Outcomes will be measured at baseline, 3 and 6 months post-randomisation. The primary outcome will be physical function assessed by the Patient-Specific Functional Scale (PSFS). Secondary outcomes include pain intensity, physical activity levels, activity limitations, quality of life, pain coping. We will also collect process evaluation data such as recruitment rate, attendance and adherence, follow-up rate, participants' opinions and any barriers encountered throughout the trial. DISCUSSION: The findings from this trial will establish the effectiveness of eHealth-delivered interventions that are known to be beneficial for people with LBP and knee OA when delivered in person. As a result, this trial will help to inform health care policy and clinical practice in Australia and beyond for those living in non-urban areas. TRIAL REGISTRATION: This study was prospectively registered on the Australian New Zealand Clinical Trials Registry ( ACTRN12618001494224 ) registered 09.05.2018.

Relationship between epicardial adipose tissue thickness and epicardial adipocyte size with increasing body mass index.

Macroscopic deposition of epicardial adipose tissue (EAT) has been strongly associated with numerous indices of obesity and cardiovascular disease risk. In contrast, the morphology of EAT adipocytes has rarely been investigated. We aimed to determine whether obesity-driven adipocyte hypertrophy, which is characteristic of other visceral fat depots, is found within EAT adipocytes. EAT samples were collected from cardiac surgery patients (n = 49), stained with haematoxylin & eosin, and analysed for mean adipocyte size and non-adipocyte area. EAT thickness was measured using echocardiography. A significant positive relationship was found between EAT thickness and body mass index (BMI). When stratified into standardized BMI categories, EAT thickness was 58.7% greater (p = 0.003) in patients from the obese (7.3 ± 1.8 mm) compared to normal (4.6 ± 0.9 mm) category. BMI as a continuous variable significantly correlated with EAT thickness (r = 0.56, p < 0.0001). Conversely, no correlation was observed between adipocyte size and either BMI or EAT thickness. No difference in the non-adipocyte area was found between BMI groups. Our results suggest that the increased macroscopic EAT deposition associated with obesity is not caused by adipocyte hypertrophy. Rather, alternative remodelling via adipocyte proliferation might be responsible for the observed EAT expansion.

A double recombinant herpes virus of turkeys for the protection of chickens against Newcastle, infectious laryngotracheitis and Marek's diseases.

A double recombinant strain of herpes virus of turkeys (HVT) was constructed that contains the fusion (F) gene from Newcastle disease virus (NDV) and the gD plus gI genes from infectious laryngotracheitis virus (ILTV) inserted into a non-essential region of the HVT genome. Expression of the F protein was controlled by a human cytomegalovirus promoter, whereas expression of gD plus gI was driven by an ILTV promoter. The double recombinant vaccine virus (HVT-NDV-ILT) was fully stable genetically and phenotypically following extended passage in cell culture and infection of chickens. Safety of the vaccine virus was confirmed by overdose and backpassage studies in specific-pathogen-free chickens. Chickens vaccinated with a single dose of HVT-NDV-ILT administered by the in ovo route were highly protected from challenge with the velogenic NDV (GB Texas), ILTV (LT 96-3) and Marek's disease virus (GA 5) strains (97%, 94% and 97%, respectively). Similarly, chickens vaccinated with a single dose by subcutaneous (SC) route at 1 day of age were highly protected from challenge with the same three viruses (100%, 100%, and 88%, respectively). The protection level of a single dose given by in ovo or SC route against challenge with a virulent Marek's disease virus strain demonstrates that insertion of multiple genes from two different pathogens within the HVT genome had no adverse effect on the capacity of HVT to protect against Marek's disease. These results demonstrate that HVT-NDV-ILT is a safe and efficacious vaccine for simultaneous control of NDV, ILTV and Marek's diseases.

Repeatability, consistency, and accuracy of hand-held dynamometry with and without fixation for measuring ankle plantarflexion strength in healthy adolescents and adults.

INTRODUCTION: Hand-held dynamometry (HHD) is commonly used to measure ankle plantarflexion strength but has variable reliability measuring higher forces. Fixed HHD is suggested to improve reliability. We, therefore, compared the reliability, consistency, and accuracy of measuring plantarflexion strength. METHODS: Plantarflexion strength was measured in 25 healthy individuals with fixed HHD and HHD alone. Intraclass correlation coefficients (ICC2,2 ), SEM, minimal detectable change, and Spearman correlation coefficients were calculated to assess inter-trial repeatability, consistency, agreement, and accuracy. RESULTS: Both methods were repeatable (ICC2,2 0.96 to 0.98) and highly correlated (Spearman rho = 0.815; P < 0.01). Fixed HHD produced significantly higher force outputs. HHD alone provided more consistent force values. CONCLUSIONS: Both methods of measuring ankle plantarflexion force were reliable. Force measured with fixed HHD will likely be more accurate for adults and individuals with greater strength, while HHD alone will be more consistent for individuals with lower strength. Muscle Nerve 56: 896-900, 2017.

PLASTID MOVEMENT IMPAIRED1 mediates ABA sensitivity during germination and implicates ABA in light-mediated Chloroplast movements.

The plant hormone abscisic acid (ABA) controls many aspects of plant growth and development, including seed development, germination and responses to water-deficit stress. A complex ABA signaling network integrates environmental signals including water availability and light intensity and quality to fine-tune the response to a changing environment. To further define the regulatory pathways that control water-deficit and ABA responses, we carried out a gene-trap tagging screen for water-deficit-regulated genes in Arabidopsis thaliana. This screen identified PLASTID MOVEMENT IMPAIRED1 (PMI1), a gene involved in blue-light-induced chloroplast movement, as functioning in ABA-response pathways. We provide evidence that PMI1 is involved in the regulation of seed germination by ABA, acting upstream of the intersection between ABA and low-glucose signaling pathways. Furthermore, PMI1 participates in the regulation of ABA accumulation during periods of water deficit at the seedling stage. The combined phenotypes of pmi1 mutants in chloroplast movement and ABA responses indicate that ABA signaling may modulate chloroplast motility. This result was further supported by the detection of altered chloroplast movements in the ABA mutants aba1-6, aba2-1 and abi1-1.

Morphological and anatomical determinants of mesophyll conductance in wild relatives of tomato (Solanum sect. Lycopersicon, sect. Lycopersicoides; Solanaceae).

Natural selection on photosynthetic performance is a primary factor determining leaf phenotypes. The complex CO2 diffusion path from substomatal cavities to the chloroplasts - the mesophyll conductance (g(m)) - limits photosynthetic rate in many species and hence shapes variation in leaf morphology and anatomy. Among sclerophyllous and succulent taxa, structural investment in leaves, measured as the leaf dry mass per area (LMA), has been implicated in decreased gm . However, in herbaceous taxa with high g(m), it is less certain how LMA impacts CO2 diffusion and whether it significantly affects photosynthetic performance. We addressed these questions in the context of understanding the ecophysiological significance of leaf trait variation in wild tomatoes, a closely related group of herbaceous perennials. Although g(m) was high in wild tomatoes, variation in g(m) significantly affected photosynthesis. Even in these tender-leaved herbaceous species, greater LMA led to reduced g(m). This relationship between g(m) and LMA is partially mediated by cell packing and leaf thickness, although amphistomy (equal distribution of stomata on both sides of the leaf) mitigates the effect of leaf thickness. Understanding the costs of increased LMA will inform future work on the adaptive significance of leaf trait variation across ecological gradients in wild tomatoes and other systems.