MRI overestimates articular cartilage thickness and volume compared to synchrotron radiation phase-contrast imaging.

Accurate evaluation of morphological changes in articular cartilage are necessary for early detection of osteoarthritis (OA). 3T magnetic resonance imaging (MRI) has highly sensitive contrast resolution and is widely used clinically to detect OA. However, synchrotron radiation phase-contrast imaging computed tomography (SR-PCI) can also provide contrast to tissue interfaces that do not have sufficient absorption differences, with the added benefit of very high spatial resolution. Here, MRI was compared with SR-PCI for quantitative evaluation of human articular cartilage. Medial tibial condyles were harvested from non-OA donors and from OA patients receiving knee replacement surgery. Both imaging methods revealed that average cartilage thickness and cartilage volume were significantly reduced in the OA group, compared to the non-OA group. When comparing modalities, the superior resolution of SR-PCI enabled more precise mapping of the cartilage surface relative to MRI. As a result, MRI showed significantly higher average cartilage thickness and cartilage volume, compared to SR-PCI. These data highlight the potential for high-resolution imaging of articular cartilage using SR-PCI as a solution for early OA diagnosis. Recognizing current limitations of using a synchrotron for clinical imaging, we discuss its nascent utility for preclinical models, particularly longitudinal studies of live animal models of OA.

Withdrawal of bevacizumab is associated with rebound growth of vestibular schwannomas in neurofibromatosis type 2-related schwannomatosis patients.

Background: Neurofibromatosis type 2 (NF2)-related schwannomatosis is an autosomal dominant tumor-predisposition syndrome characterized by bilateral vestibular schwannomas (VS). In patients with VS associated with NF2, vascular endothelial growth factor A inhibitor, bevacizumab, is a systemic treatment option. The aim of this study is to retrospectively evaluate NF2 patient responses to bevacizumab on VS growth and symptom progression. Methods: This is a retrospective analysis of patients seen at the Mayo Clinic Rochester Multidisciplinary NF2 Clinic. Results: Out of 76 patients with NF2 evaluated between 2020 and 2022, we identified 19 that received treatment with bevacizumab. Thirteen of these patients discontinued bevacizumab after median treatment duration of 12.2 months. The remaining 6 patients are currently receiving bevacizumab treatment for a median duration of 9.4 months as of March, 2023. Fifteen patients had evaluable brain MRI data, which demonstrated partial responses in 5 patients, stable disease in 8, and progression in 2. Within 6 months of bevacizumab discontinuation, 5 patients had rebound growth of their VS greater than 20% from their previous tumor volume, while 3 did not. Three patients with rebound growth went on to have surgery or irradiation for VS management. Conclusions: Our single-institution experience confirms prior studies that bevacizumab can control progression of VS and symptoms associated with VS growth. However, we note that there is the potential for rapid VS growth following bevacizumab discontinuation, for which we propose heightened surveillance imaging and symptom monitoring for at least 6 months upon stopping anti-VEGF therapy.

Sub-1.4 cm3 capsule for detecting labile inflammatory biomarkers in situ.

Transient molecules in the gastrointestinal tract such as nitric oxide and hydrogen sulfide are key signals and mediators of inflammation. Owing to their highly reactive nature and extremely short lifetime in the body, these molecules are difficult to detect. Here we develop a miniaturized device that integrates genetically engineered probiotic biosensors with a custom-designed photodetector and readout chip to track these molecules in the gastrointestinal tract. Leveraging the molecular specificity of living sensors1, we genetically encoded bacteria to respond to inflammation-associated molecules by producing luminescence. Low-power electronic readout circuits2 integrated into the device convert the light emitted by the encapsulated bacteria to a wireless signal. We demonstrate in vivo biosensor monitoring in the gastrointestinal tract of small and large animal models and the integration of all components into a sub-1.4 cm3 form factor that is compatible with ingestion and capable of supporting wireless communication. With this device, diseases such as inflammatory bowel disease could be diagnosed earlier than is currently possible, and disease progression could be more accurately tracked. The wireless detection of short-lived, disease-associated molecules with our device could also support timely communication between patients and caregivers, as well as remote personalized care.

A comparison of self-reported risk and protective factors and the death implicit association test in the prediction of future suicide attempts in adolescent emergency department patients.

BACKGROUND: Concerns have been raised about the utility of self-report assessments in predicting future suicide attempts. Clinicians in pediatric emergency departments (EDs) often are required to assess suicidal risk. The Death Implicit Association Test (IAT) is an alternative to self-report assessment of suicidal risk that may have utility in ED settings. METHODS: A total of 1679 adolescents recruited from 13 pediatric emergency rooms in the Pediatric Emergency Care Applied Research Network were assessed using a self-report survey of risk and protective factors for a suicide attempt, and the IAT, and then followed up 3 months later to determine if an attempt had occurred. The accuracy of prediction was compared between self-reports and the IAT using the area under the curve (AUC) with respect to receiver operator characteristics. RESULTS: A few self-report variables, namely, current and past suicide ideation, past suicidal behavior, total negative life events, and school or social connectedness, predicted an attempt at 3 months with an AUC of 0.87 [95% confidence interval (CI), 0.84-0.90] in the entire sample, and AUC = 0.91, (95% CI 0.85-0.95) for those who presented without reported suicidal ideation. The IAT did not add significantly to the predictive power of selected self-report variables. The IAT alone was modestly predictive of 3-month attempts in the overall sample ((AUC = 0.59, 95% CI 0.52-0.65) and was a better predictor in patients who were non-suicidal at baseline (AUC = 0.67, 95% CI 0.55-0.79). CONCLUSIONS: In pediatric EDs, a small set of self-reported items predicted suicide attempts within 3 months more accurately than did the IAT.

Review of the leafhopper genus Drabescus Stl (Hemiptera: Cicadellidae: Deltocephalinae) in the Indian subcontinent with description of one new species.

The leafhopper genus Drabescus Stl is reviewed for the Indian subcontinent with one new species described, D. austroindicus sp. nov. (India: Tamil Nadu). A checklist and key to the species from the Indian subcontinent are given.

The RAIS Device for Global Surgery: Using a Participatory Design Approach to Navigate the Translational Pathway to Clinical Use.

BACKGROUND: Over 5 billion people worldwide have no access to surgery worldwide, typically in low-resource settings, despite it being a primary life-saving treatment. Gas Insufflation-Less Laparoscopic Surgery (GILLS) can address this inequity, by improving current GILLS instrumentation to modern surgical standards. OBJECTIVE: to develop and translate a new Retractor for Abdominal Insufflation-less Surgery (RAIS) into clinical use and thus provide a context-appropriate system to advance GILLS surgery. METHODS: A collaborative multidisciplinary team from the UK and India was formed, embedding local clinical stakeholders and an industry partner in defining user and contextual needs. System development was based on a phased roadmap for 'surgical device design in low resource settings' and embedded participatory and frugal design principles in an iterative process supported by traditional medical device design methodologies. Each phase of development was evaluated by the stakeholder team through interactive workshops using cadaveric surgical simulations. A Commercialisation phase undertook Design to Manufacture and regulatory approval activities. Clinical validation was then conducted with rural surgeons performing GILLS procedures using the RAIS system. Semi-structured questionnaires and interviews were used to evaluate device performance. RESULTS: A set of user needs and contextual requirements were defined and formalised. System development occurred across five iterations. Stakeholder participation was instrumental in converging on a design which met user requirements. A commercial RAIS system was then produced by an industry partner under Indian regulatory approval. This was successfully used in clinical validation to conduct 12 surgical procedures at two locations in rural India. Surgical feedback showed that the RAIS system provided a valuable and usable surgical instrument which was appropriate for use in low-resource contexts. CONCLUSIONS: Using a context-specific development approach with close engagement of stakeholders was crucial to develop the RAIS system for low-resource regions. The outcome is translation from global health need into a fully realized commercial instrument which can be used by surgeons in low-resource regions across India.

Developing a Microbubble-Based Contrast Agent for Synchrotron Multiple-Image Radiography.

PURPOSE: Multiple-image radiography (MIR) is an analyzer-based synchrotron X-ray imaging approach capable of dissociating absorption, refraction, and scattering components of X-ray interaction with the material. It generates additional image contrast mechanisms (besides absorption), especially in the case of soft tissues, while minimizing absorbed radiation dose. Our goal is to develop a contrast agent for MIR using ultrasound microbubbles by carrying out a systematic assessment of size, shell material, and concentration. PROCEDURES: Microbubbles were synthesized with two different shell materials: phospholipid and polyvinyl-alcohol. Polydisperse perfluorobutane-filled lipid microbubbles were divided into five size groups using centrifugation. Two distributions of air-filled polymer microbubbles were generated: 2-3 µm and 3-4 µm. A subset of polymer microbubbles 3-4 µm had iron oxide nanoparticles incorporated into their shell or coated on their surface. Microbubbles were immobilized in agar with different concentrations: 5 × 107, 5 × 106, and 5 × 105 MBs/ml. MIR was conducted on the BioMedical Imaging and Therapy beamline at the Canadian Light Source. Three images were generated: Gaussian amplitude, refraction, and ultra-small-angle X-ray scattering (USAXS). The contrast signal was quantified by measuring mean pixel values and comparing them with agar. RESULTS: No difference was detected in absorption or refraction images of all tested microbubbles. Using USAXS, a significant signal increase was observed with lipid microbubbles 6-10 µm at the highest concentration (p = 0.02), but no signal was observed at lower concentrations. CONCLUSIONS: These data indicate that lipid microbubbles 6-10 µm are candidates as contrast agents for MIR, specifically for USAXS. A minimum concentration of 5 × 107 microbubbles (lipid-shell 6-10 µm) per milliliter was needed to generate a detectable signal.

Review of the leafhopper genus Protensus/ Zhang amp; Dai (Hemiptera, Cicadellidae, Deltocephalinae) with description of a new species.

Species of the leafhopper genus Protensus Zhang Dai, 2001 (Deltocephalinae: Athysanini) from Japan and China are reviewed, and a new species Protensus lii sp. nov. is described and illustrated from China. Protensus nigrifrons Li Xing, 2011 is treated as incertae sedis in the tribe Mukariini (Deltocephalinae). A checklist and key to species of Protensus is provided.

Can an introduced predator select for adaptive sex allocation?

Most species produce equal numbers of sons and daughters, and sex differences in survival after parental care do not usually affect this pattern. Temporary overproduction of the scarcer sex can be adaptive when generations overlap, the sexes differ in life-history expectations, and parents can anticipate future mating opportunities. However, an alternative strategy of maximizing the competitiveness of the more abundant sex in these circumstances remains unexplored. We develop theory showing how mothers can maximize reproductive value when future mate competition will be high by producing more sons in the advantageous early hatching positions within their broods. Our model for optimal birth order was supported by long-term data of offspring sex in a parrot facing catastrophic female mortality caused by introduced predators. Swift parrots (Lathamus discolor) suffer high female mortality due to introduced sugar gliders (Petaurus breviceps) creating fluctuating male-biased adult sex ratios. Offspring hatched early within broods fledged in better condition, and in support of our model were more likely to be male in years with higher adult female mortality. We found a highly significant rank-order correlation between observed and predicted birth sex ratios. Our study shows the potential for mothers to maximize reproductive value via strategic biases in offspring sex depending on the advantages conferred by birth order and the predictability of future mate competition. Our long-term data support the predictions and appear to suggest that sex allocation strategies may evolve surprisingly quickly when anthropogenic pressures on populations are severe.

Four new species of Mileewini leafhoppers (Hemiptera: Cicadellidae: Mileewinae) from China, with a checklist to Chinese species.

Four new species of Mileewini, Mileewa clavata He Yang, sp. nov., Mileewa rubricosta He Yang, sp. nov., Mileewa quinquemaculata He Yang, sp. nov. and Ujna liboensis He Yang, sp. nov., are described and illustrated. A checklist of all Chinese Mileewini is provided.

Leafhopper subfamily Ledrinae of the Indian subcontinent: 1. Description of Yelahanka gen. nov. (Hemiptera: Cicadellidae) with seven new species and new combinations.

One new genus of the tribe Ledrini, Yelahanka gen. nov. is described with Petalocephala granulosa Distant as its type species. The genus is characterised by the flexing of the forewing laterad of a strongly carinate or keeled outer claval vein and the claval veins fused in the distal two thirds. Seven new species, Yelahanka canaraica sp. nov. (India: Karnataka), Y. kodaiensis sp. nov. (India: Tamil Nadu), Y. montana sp. nov. (India: Tamil Nadu), Y. nepalica sp. nov. (Nepal), Y. sikkimensis sp. nov. (India: Sikkim), Y. shillongensis sp. nov. (India: Meghalaya) and Y. trifida sp. nov. (India: Himachal Pradesh, Arunachal Pradesh) are described and illustrated. The following new combinations are proposed: Yelahanka bainbriggei (Distant) comb. nov., Y. granulosa (Distant) comb. nov., Y. punctata (Walker) comb. nov. and Y. tabulata (Distant) comb. nov.; originally punctata was placed in the genus Ledra Fabricius and remaining species were placed in Petalocephala Stål. Petalocephala bainbriggei Distant 1916 is treated as a junior synonym of Y. granulosa (Distant 1910) syn. nov. and P. tabulata Distant 1908 is treated as a junior synonym of Yelahanka punctata (Walker 1851) syn. nov. Y. granulosa is newly recorded from Africa (Tanzania and Kenya) and Malaya. Relationships of the new genus with other genera of Ledrini are discussed and a key to species of the genus is also provided.

Effects of liraglutide versus sitagliptin on circulating cardiovascular biomarkers, including circulating progenitor cells, in individuals with type 2 diabetes and obesity: Analyses from the LYDIA trial.

The mechanisms behind the beneficial cardiovascular effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) compared with dipeptidyl peptidase-4 inhibitors (DPP4is) remain largely unknown, despite both targeting the incretin pathway to improve glycaemic control. In these prespecified secondary analyses of the LYDIA trial, we examined the impact of the GLP-1RA liraglutide (1.8 mg once-daily) and the DPP4i sitagliptin (100 mg once-daily) on circulating cardiovascular biomarkers associated with atherosclerotic risk, including circulating progenitor cells (CPCs). LYDIA was a 26-week, randomized, active-comparator trial in 61 adults with type 2 diabetes and obesity (mean ± SD: age 43.8 ± 6.5 years, body mass index 35.3 ± 6.4 kg/m2 , HbA1c 7.5% ± 0.83% [58.5 ± 9.1 mmol/mol]). Vascular endothelial growth factor (VEGF) and stromal cell-derived factor-1-alpha (SDF-1ɑ), both of which are implicated in endothelial function, were higher at 26 weeks with liraglutide therapy compared with sitagliptin (mean between-group difference [95% CI]: 77.03 [18.29, 135.77] pg/mL, p = .010; and 996.25 [818.85, 1173.64] pg/mL, p < .001, respectively). There were no between-group differences in CPCs, nitric oxide, C-reactive protein, interleukin-6, tumour necrosis factor alpha and advanced glycation end-products. These analyses suggest a favourable impact of liraglutide on VEGF and SDF-1ɑ levels compared with sitagliptin. These factors may therefore be implicated in the differential cardiovascular effects observed between these agents in large cardiovascular outcome trials. However, these are secondary analyses from a previous trial and thus hypothesis-generating. Purposive trials are required to examine these findings further.

A new species of the Oriental leafhopper genus Kutara Distant (Hemiptera: Cicadellidae: Deltocephalinae) from Vietnam.

The Oriental leafhopper genus Kutara Distant, 1908 (Cicadellidae: Deltocephalinae: Drabescini: Paraboloponina) is newly recorded from Vietnam with description of a new species K. trispinosa Xu Zhang sp. nov.. An updated checklist, with distribution and a key to males of Kutara, are also provided. The type specimens of the new species are deposited in the Muséum National d'Histoire Naturelle, Paris, France (MNHN) and the Illinois Natural History Survey, University of Illinois, Champaign, Illinois, USA (INHS).

Leafhopper tribe Stegelytrini (Hemiptera: Cicadellidae: Deltocephalinae) of the Indian subcontinent, with a note on Aeternus hieroglyphicus Distant (Cicadellidae: Athysanini).

A checklist of leafhoppers of the tribe Stegelytrini from the Indian subcontinent and a key to genera are given.  Two new species, Pachymetopius anamikus sp. nov. (India: Meghalaya) and Yaontogonia unipuncta sp. nov. (India: Arunachal Pradesh) are described and illustrated. Genus Aeternus Distant with its type species A. hieroglyphicus Distant is redescribed based on the male genitalia and its tribal placement is discussed. Habitus images of types of species except Aculescutellaris hirtellus Zhang, Wei Webb are given.

An Assessment of Earth's Climate Sensitivity Using Multiple Lines of Evidence.

We assess evidence relevant to Earth's equilibrium climate sensitivity per doubling of atmospheric CO2, characterized by an effective sensitivity S. This evidence includes feedback process understanding, the historical climate record, and the paleoclimate record. An S value lower than 2 K is difficult to reconcile with any of the three lines of evidence. The amount of cooling during the Last Glacial Maximum provides strong evidence against values of S greater than 4.5 K. Other lines of evidence in combination also show that this is relatively unlikely. We use a Bayesian approach to produce a probability density function (PDF) for S given all the evidence, including tests of robustness to difficult-to-quantify uncertainties and different priors. The 66% range is 2.6-3.9 K for our Baseline calculation and remains within 2.3-4.5 K under the robustness tests; corresponding 5-95% ranges are 2.3-4.7 K, bounded by 2.0-5.7 K (although such high-confidence ranges should be regarded more cautiously). This indicates a stronger constraint on S than reported in past assessments, by lifting the low end of the range. This narrowing occurs because the three lines of evidence agree and are judged to be largely independent and because of greater confidence in understanding feedback processes and in combining evidence. We identify promising avenues for further narrowing the range in S, in particular using comprehensive models and process understanding to address limitations in the traditional forcing-feedback paradigm for interpreting past changes.

Patella dislocation: an online systematic video analysis of the mechanism of injury.

BACKGROUND: The mechanism of injury (MoI) for a patellar dislocation has not been fully established. The aim of this study was to use systematic video analysis to determine the MoI of a patella dislocation. METHODS: A systematic search was conducted of three video sharing websites and three popular search engines to identify videos demonstrating a patellar dislocation. Videos were reviewed by three surgeons trained in systematic video analysis, who commented on the position of the lower limb and the situation in which the injury occurred. The results were reviewed to build a consensus of the MoI for each video. Statistical analysis was conducted for interobserver agreement (p < 0.05). RESULTS: Initial search yielded 603 videos with 13 meeting the inclusion criteria. The injuries were sustained performing a sporting activity (n = 9) or whilst dancing (n = 4). The injury was predominantly sustained during a non-contact situation (n = 10). The most common mechanism was an unbalanced individual with a flexed hip sustaining a valgus force to their flexed knee with the tibia externally rotated. CONCLUSIONS: This study provides some insight into the MoI for a patellar dislocation and the findings may assist in developing injury prevention programmes and rehabilitation protocols as well as guiding future research.

A randomized, open-label, active comparator trial assessing the effects of 26 weeks of liraglutide or sitagliptin on cardiovascular function in young obese adults with type 2 diabetes.

AIM: To compare the effects of a glucagon-like peptide-1 receptor agonist and a dipeptidyl peptidase-4 inhibitor on magnetic resonance imaging-derived measures of cardiovascular function. MATERIALS AND METHODS: In a prospective, randomized, open-label, blinded endpoint trial liraglutide (1.8 mg) and sitagliptin (100 mg) were compared in asymptomatic, non-insulin treated young (aged 18-50 years) adults with obesity and type 2 diabetes. The primary outcome was difference in circumferential peak early diastolic strain rate change (PEDSR), a biomarker of cardiac diastolic dysfunction 26 weeks after randomization. Secondary outcomes included other indices of cardiac structure and function, HbA1c and body weight. RESULTS: Seventy-six participants were randomized (54% female, mean ± SD age 44 ± 6 years, diabetes duration 4.4 years, body mass index 35.3 ± 6.1 kg m-2 ), of whom 65% had ≥1 cardiovascular risk factor. Sixty-one participants had primary outcome data available. There were no statistically significant between-group differences (intention-to-treat; mean [95% confidence interval]) in PEDSR change (-0.01 [-0.07, +0.06] s-1 ), left ventricular ejection fraction (-1.98 [-4.90, +0.94]%), left ventricular mass (+1.14 [-5.23, +7.50] g) or aortic distensibility (-0.35 [-0.98, +0.28] mmHg-1 × 10-3 ) after 26 weeks. Reductions in HbA1c (-4.57 [-9.10, -0.37] mmol mol-1 ) and body weight (-3.88 [-5.74, -2.01] kg) were greater with liraglutide. CONCLUSION: There were no differences in cardiovascular structure or function after short-term use of liraglutide and sitagliptin in younger adults with obesity and type 2 diabetes. Longer studies in patients with more severe cardiac dysfunction may be necessary before definitive conclusions can be made about putative pleiotropic properties of incretin-based therapies.

The effects of sodium reduction on the gas phase of bread doughs using synchrotron X-ray microtomography.

Globally, the bakery industry has a target of reducing sodium content in bread products. However, removing salt results in changes in the quality of bread through effects on dough's gas phase during the breadmaking process. Using synchrotron X-ray microtomography, the objective of this study was to investigate how sodium reduction induced changes in the gas phase parameters (i.e., gas volume fraction, bubble size distribution (BSD) and its time evolution) of non-yeasted doughs made from a wide range of formulations (i.e., wheat cultivar and water content) prepared with different mixing times. As salt content was reduced, a lower gas volume was retained in the dough by the end of mixing. Less gas bubbles were also retained if doughs were prepared from a stronger wheat cultivar, higher water content, and/or mixed for a shorter time. Rates of change in the median (R0) and the width (ε) of the fitted lognormal radius dependence of bubble volume fraction [BVF(R)] indicated that reduced sodium content permitted disproportionation to proceed more rapidly. Higher water content or longer mixing time also resulted in faster disproportionation, indicating that water content and mixing time can be manipulated as a means of increasing bubble stability against disproportionation during low-sodium breadmaking. An examination of relative changes in dough's gas phase parameters arising from sodium reduction demonstrated that wheat cultivar, water content and mixing time all affected dough's tolerance to sodium reduction. Therefore, attainment of good bread crumb cell structure in low-sodium bread formulas is a function of salt's effects on dough rheology in addition to its effect on yeast activity, so that dough formulation and mixing conditions also need to be considered.

When does the patella dislocate? A systematic review of biomechanical & kinematic studies.

BACKGROUND: Patellar dislocations are a significant injury with the potential for long term problems. Little work has been done on establishing the mechanism by which this injury occurs. OBJECTIVES: To determine the mechanism of injury of a patella dislocation based on the available published literature and compare them to already proposed theories. METHODS: A systematic review of the literature was conducted following searches performed on MEDLINE, EMBASE and ProQuest from the earliest year of indexing using the following search terms in any combination: "patella", "dislocation", "mechanism of injury", "anatomy", "biomechanical" and "risk factor". A broad inclusion criteria was used that included studies that looked at patellar dislocations and instability with respect to the patellofemoral joint (PFJ) kinematics or altered kinematics of the PFJ. Studies that did not address the kinematics or biomechanics of the PFJ were excluded. Studies were appraised based on their methodology using a combination of the Critical Appraisal Skills Programme tool and the Quality Appraisal for Cadaveric Studies. RESULTS: 113 studies were identified from a search of MEDLINE, EMBASE and ProQuest databases. Following application of our inclusion criteria, a total of 23 studies were included in our review. 18 of these studies were cadaveric biomechanical studies. The remaining studies were anatomical, imaging based, and a computer simulation based study. CONCLUSIONS: These biomechanical and kinematic studies provide some evidence that a dislocation is likely to occur during early knee flexion with external rotation of the tibia and contraction of the quadriceps. There is limited evidence to support other elements of proposed mechanisms of dislocation.