Lightning Pose: improved animal pose estimation via semi-supervised learning, Bayesian ensembling and cloud-native open-source tools.

Contemporary pose estimation methods enable precise measurements of behavior via supervised deep learning with hand-labeled video frames. Although effective in many cases, the supervised approach requires extensive labeling and often produces outputs that are unreliable for downstream analyses. Here, we introduce 'Lightning Pose', an efficient pose estimation package with three algorithmic contributions. First, in addition to training on a few labeled video frames, we use many unlabeled videos and penalize the network whenever its predictions violate motion continuity, multiple-view geometry and posture plausibility (semi-supervised learning). Second, we introduce a network architecture that resolves occlusions by predicting pose on any given frame using surrounding unlabeled frames. Third, we refine the pose predictions post hoc by combining ensembling and Kalman smoothing. Together, these components render pose trajectories more accurate and scientifically usable. We released a cloud application that allows users to label data, train networks and process new videos directly from the browser.

Treatment of type 2 diabetes with the designer cytokine IC7Fc.

The gp130 receptor cytokines IL-6 and CNTF improve metabolic homeostasis but have limited therapeutic use for the treatment of type 2 diabetes. Accordingly, we engineered the gp130 ligand IC7Fc, in which one gp130-binding site is removed from IL-6 and replaced with the LIF-receptor-binding site from CNTF, fused with the Fc domain of immunoglobulin G, creating a cytokine with CNTF-like, but IL-6-receptor-dependent, signalling. Here we show that IC7Fc improves glucose tolerance and hyperglycaemia and prevents weight gain and liver steatosis in mice. In addition, IC7Fc either increases, or prevents the loss of, skeletal muscle mass by activation of the transcriptional regulator YAP1. In human-cell-based assays, and in non-human primates, IC7Fc treatment results in no signs of inflammation or immunogenicity. Thus, IC7Fc is a realistic next-generation biological agent for the treatment of type 2 diabetes and muscle atrophy, disorders that are currently pandemic.

Lightning Pose: improved animal pose estimation via semi-supervised learning, Bayesian ensembling, and cloud-native open-source tools.

Contemporary pose estimation methods enable precise measurements of behavior via supervised deep learning with hand-labeled video frames. Although effective in many cases, the supervised approach requires extensive labeling and often produces outputs that are unreliable for downstream analyses. Here, we introduce "Lightning Pose," an efficient pose estimation package with three algorithmic contributions. First, in addition to training on a few labeled video frames, we use many unlabeled videos and penalize the network whenever its predictions violate motion continuity, multiple-view geometry, and posture plausibility (semi-supervised learning). Second, we introduce a network architecture that resolves occlusions by predicting pose on any given frame using surrounding unlabeled frames. Third, we refine the pose predictions post-hoc by combining ensembling and Kalman smoothing. Together, these components render pose trajectories more accurate and scientifically usable. We release a cloud application that allows users to label data, train networks, and predict new videos directly from the browser.

The correlation between coronal balance and neuroaxial abnormalities detected on MRI in adolescent idiopathic scoliosis.

INTRODUCTION: The indications for magnetic resonance imaging in presumed adolescent idiopathic scoliosis (AIS) have not been established, with some studies suggesting that rates of spinal cord abnormalities are low and question the use of the routine MRI in AIS. OBJECTIVE: Given the restraints on MRI resources the authors performed a retrospective audit to see if the presence of coronal or sagittal misbalance-balance could be used as a surrogate marker for the presence of spinal cord abnormalities in this patient group and hence reduce the need for unnecessary MRI scans. METHODS: We performed a retrospective review of imaging of patients with AIS at our centre over a 2-year-period. All MRI scans were reported by the senior author and the presence of spinal cord abnormalities noted. All plain films were assessed by a senior SpR and ST2 orthopaedic surgeons for Cobb angle, coronal balance, sagittal balance and Lenke classification. RESULTS: A total of 171 patients were identified with AIS. Of these, a total of 15 patients (9%) were found to have neural axis anomalies on MRI including syringomyelia, Chiari malformations and dural ectasia. The average Cobb angle was 44.9° with coronal balance varying from 67.2 mm left to 40.2 mm right. Sagittal balance varied from 125 mm negative to 83 mm positive. No correlation was found between coronal/sagittal misbalance and the presence of neural axis anomalies. CONCLUSIONS: Our audit demonstrates that neither coronal nor sagittal misbalance should be used as an indicator of neural axis abnormalities.

Where are children seen in Australian emergency departments? Implications for research efforts.

OBJECTIVE: With most paediatric emergency research in Australia conducted at tertiary EDs, it is important to understand how presentations differ between those at tertiary paediatric EDs and all other EDs. METHODS: Retrospective epidemiological study assessing paediatric case-mix and time-based performance metrics (aged 0-14 years) obtained from a national health service minimum dataset for the 2017-2018 financial year, comparing tertiary paediatric EDs and all other EDs. We defined a 'major tertiary paediatric hospital' as one which was accredited for training in both paediatric emergency medicine and paediatric intensive care. RESULTS: Of the 1 695 854 paediatric ED presentations, 23.8% were seen in nine major metropolitan tertiary paediatric hospitals. Reasons for presentations were more distinctive between cohorts among children aged 10-14 years, where psychiatric illness (5.2% vs 2.5%) and neurological illness (4.5% vs 2.5%) were more commonly seen in major tertiary paediatric EDs. Australian Indigenous children were significantly less likely to present to tertiary paediatric EDs (3.0%), compared with other EDs (9.7%) (odds ratio 0.27, 95% confidence interval 0.26-0.27). While median waiting times were longer in major tertiary paediatric EDs (28 min [interquartile range 11-65]) than in other EDs (20 min [interquartile range 8-48], P < 0.001), patients were also less likely to leave without being seen (5.5% in tertiary paediatric EDs vs 6.9% in other EDs; odds ratio 0.80, 95% confidence interval 0.78-0.81). CONCLUSIONS: The present study identified key areas of difference in paediatric presentations between tertiary paediatric EDs and other EDs. It is vital to broaden paediatric ED research beyond tertiary paediatric centres, to ensure relevance and generalisability.

Impact of massage therapy on motor outcomes in very low-birthweight infants: randomized controlled pilot study.

BACKGROUND: The purpose of the present study was to determine the effects of massage therapy on motor development, weight gain, and hospital discharge in preterm very low-birthweight (VLBW) newborns. METHODS: Twenty-four preterm VLBW newborns (<34 weeks and <1500 g) were enrolled in this randomized controlled pilot study. The intervention group (n = 12) received massage therapy starting at 34 weeks post-conceptional age (15 min daily, 5 days/week for 4 weeks). The infants in the sham treatment group (n = 12) received similar duration of light still touch. Test of Infant Motor Performance (TIMP) score gain, weight gain, and post-conceptional age at discharge were compared between the two groups after intervention using Mann-Whitney U-test. RESULTS: No significant between-group difference in TIMP score gain and weight gain was identified when all subjects were analyzed. In subgroup analysis, among those with below-average pre-treatment TIMP score (<35), the intervention group (n = 6) achieved significantly higher TIMP score gain (P = 0.043) and earlier hospital discharge (P = 0.045) than the sham treatment group (n = 5). These same infants, however, also had significantly shorter duration of total parenteral nutrition than their counterparts in the sham treatment group (P = 0.044). CONCLUSIONS: Massage therapy might be a viable intervention to promote motor outcomes in a subgroup of VLBW newborns with poor motor performance. A larger randomized controlled trial is required to further explore the effects of massage therapy in this high-risk group.

A novel duplication at the putative DNA polymerase alpha arrest site and a founder mutation in Chinese in the IVD gene underlie isovaleric acidaemia.

Isovaleric acidaemia is a rare inherited organic acidaemia associated with a characteristic odour in affected patients. Fewer than 40 causative mutations have been reported to date. We report a case in a Hong Kong Chinese neonate who presented with respiratory distress and acute encephalopathy requiring aggressive resuscitation and treatment. Residual gross motor developmental delay was still observed at the age of 16 months. The child was subsequently found to harbour a known missense mutation (c.A1199G [p.Y371C]) and a novel 4-bp duplication (c.1148_1151dupGCTA [p.Y355X]) in the IVD gene. We suggest that the former is a founder mutation in the Chinese population and propose an explanation for the duplication event. Strategies that may achieve early diagnosis and prompt treatment include raising awareness of this condition, implementation of a tandem mass spectrometry neonatal screening programme, and local acquisition of appropriate medications for these metabolic diseases.

Timing of surgery and radiotherapy in the management of metastatic spine disease: expert opinion.

BACKGROUND: Combined surgery and radiotherapy, in the treatment of metastatic disease of the spine, is now emerging as the gold standard of care where there is an indication for spinal stabilization and/or surgical decompression. However potential complications related to wound healing can occur with radiation delivered shortly before or after to surgery. The purpose of this study was to understand the practice of leading radiation oncologists and spine surgeons with regards to the timing of radiation (conventional and stereotactic) and surgery for the management of spinal metastases. METHODS: Questionnaires were sent to leading radiation oncologists and spine surgeons throughout North America and completed via mail, email or internet. RESULTS: Eighty-six responses were received from radiation oncologists and 27 from spine surgeons. A total of 58% recommended waiting either 1 or 2 weeks after radiotherapy before operating on patients with spinal metastases. With radiotherapy administered after surgery, 62% of respondents suggested either a 1 or 2 weeks interval was sufficient. CONCLUSIONS: There appeared to be no significant difference in practice with the use of stereotactic radiotherapy though surgeons tend to accept a shorter interval in this subset of patients. We recommend that the interval between radiotherapy and surgery (and vice versa) should ideally be a minimum of 2 weeks.

Carnitine-acylcarnitine translocase deficiency in three neonates presenting with rapid deterioration and cardiac arrest.

We report on three Chinese neonates with carnitine-acylcarnitine translocase deficiency. They presented within the first 48 hours of life. Two neonates were found in cardiac arrest; one of them survived after resuscitation. The third neonate suddenly developed cardiorespiratory insufficiency and succumbed eventually. The clustering of three cases in 5 years suggests that carnitine-acylcarnitine translocase deficiency is not rare in our Chinese population. We advocate that investigation for metabolic diseases including carnitine-acylcarnitine translocase deficiency should be performed in cases of sudden infant death and unexplained abrupt clinical deterioration in the early neonatal period. Non-ketotic hypoglycaemia is an early clue. The mainstay of initial treatment is glucose infusion at a rate greater than 7 mg/kg/minute, which inhibits beta-oxidation of fatty acids (the defective enzymatic steps in carnitine-acylcarnitine translocase deficiency) and thus prevents the accumulation of toxic long-chain acylcarnitines.

Inbred FVB/N mice are mutant at the cp49/Bfsp2 locus and lack beaded filament proteins in the lens.

PURPOSE: FVB/N is considered an ideal inbred mouse strain for transgenic mouse production because of the ease of pronuclear microinjection and its overall fecundity. It is well established that vertebrate lens fiber cells normally express a modified intermediate filament network consisting of the proteins filensin and CP49, and it was recently reported that the mouse strain 129 harbors mutations in CP49 that have the potential to confound the interpretation of gene knockout studies of the lens. The purpose of this study was to evaluate the status of the CP49/Bfsp2 gene in the FVB/N strain. METHODS: PCR analysis of genomic DNA was used to evaluate the status of the CP49 gene in FVB/N mice procured from the four major US distributors of these animals--Harlan Laboratories, Taconic Farms, Jackson Laboratory, and the NIH/NCI/DCT production facility run by Charles River Laboratories. The structure of the CP49 transcript was evaluated by RT-PCR, and the presence of CP49 protein in the lens was evaluated by immunofluorescence. RESULTS: FVB/N mice obtained from all four US distributors were shown to harbor a 6-kb deletion of the CP49 gene identical with that previously reported in mouse strain 129; C57BL/6 mice did not have this modification. Immunofluorescence demonstrated that FVB/N mice do not have detectable CP49 or filensin protein in the lens, whereas C57BL/6 mice have the expected protein distribution. CONCLUSIONS: In humans, mutations in the CP49/BFSP2 gene have been linked to familial, congenital cataract, demonstrating an important role of this gene in lens transparency. The demonstration that FVB/N mice lack CP49 protein in the lens suggests that it may be necessary to reevaluate the mechanisms underlying lens phenotypes obtained as a result of transgenic manipulation of this strain.

Central immunotolerance in transgenic mice expressing a foreign antigen under control of the rhodopsin promoter.

PURPOSE: Different conclusions have been reached in recent studies concerning the immune response or tolerance of transgenic (Tg) mice expressing foreign antigens under control of retinal antigen promoters. The present study was aimed at analyzing the state of tolerance in Tg mice expressing hen egg lysozyme (HEL) under control of the rhodopsin promoter. METHODS: Tg mice expressing HEL under control of the rhodopsin promoter (RhHEL-Tg) were generated and tested by conventional methods for immune responses against HEL. These Tg mice were also mated with Tg mice expressing HEL-specific receptor on their T lymphocytes and the double-Tg mice were examined for increased apoptosis in their thymi by the TUNEL assay, as well as for loss of HEL-specific T cells, by flow cytometry and proliferative response. The presence of HEL mRNA in mouse thymi was determined by RT-PCR. RESULTS: RhHEL-Tg mice developed tolerance to HEL, shown by reduced cellular and humoral responses to HEL, as well as by the failure of ocular inflammation to develop after immunization with HEL. RhHEL-Tg mice expressed HEL mRNA in their thymus, and the tolerogenic mechanism in these mice was shown to be thymic deletion of HEL-specific T cells by the following observations in the double-Tg mice: (1) increased apoptosis in their thymi, (2) remarkable reduction in the proportion of the HEL-specific T cells, and (3) loss of lymphocyte response to low concentrations of HEL. CONCLUSIONS: Tg mice expressing HEL under control of the rhodopsin promoter develop a tolerance for the foreign antigen, apparently as a result of thymic expression of HEL and deletion of T cells specific to this antigen.

Effect of occlusion on the percutaneous penetration of linoleic acid and glycerol.

The effect of occlusion on the in vitro percutaneous absorption of linoleic acid was investigated. A greater skin concentration of linoleic acid from an ethanolic vehicle was observed in non-occluded experiments compared with occluded experiments (P<0.05). Such changes were not observed as consistently when ethanol was replaced with a less volatile organic solvent (cyclomethicone). These observations were attributed to the increase in the concentration gradient due to the unimpeded evaporation of volatile solvents, which provided a greater driving force and enhanced non-occluded delivery in these systems, compared with occluded systems. Conversely, the percutaneous absorption of a polar material (glycerol) from an aqueous solution did not yield any such differences. While more conclusive comparisons between volatile and non-volatile solvents and penetrants would be required to substantiate fully these comparisons, it is apparent that non-occlusion of volatile solvents may enhance percutaneous absorption. The physicochemical properties of the penetrant, for example its natural state at skin temperature (i.e. solid or liquid) may further determine the degree of enhanced percutaneous absorption compared with occluded environments.

Evidence-based multidisciplinary practice: improving the safety and standards of male bladder catheterization.

A series of nursing care variances related to the procedure of catheterizing male patients stimulated an evidence-based practice project designed to define best practice for the technique of inserting male catheters. Results indicate current nursing knowledge may be inadequate.

Surgeon-industry conflict of interest: survey of opinions regarding industry-sponsored educational events and surgeon teaching: clinical article.

OBJECT: Conflict of interest (COI) as it applies to medical education and training has become a source of considerable interest, debate, and regulation in the last decade. Companies often pay surgeons as faculty for educational events and often sponsor and give financial support to major professional society meetings. Professional medical societies, industry, and legislators have attempted to regulate potential COI without consideration for public opinion. The practice of evidence-based medicine requires the inclusion of patient opinion along with best available evidence and expert opinion. The primary goal of this study was to assess the opinion of the general population regarding surgeon-industry COI for education-related events. METHODS: A Web-based survey was administered, with special emphasis on the surgeon's role in industry-sponsored education and support of professional societies. A survey was constructed to sample opinions on reimbursement, disclosure, and funding sources for educational events. RESULTS: There were 501 completed surveys available for analysis. More than 90% of respondents believed that industry funding for surgeons' tuition and travel for either industry-sponsored or professional society educational meetings would either not affect the quality of care delivered or would cause it to improve. Similar results were generated for opinions on surgeons being paid by industry to teach other surgeons. Moreover, the majority of respondents believed it was ethical or had no opinion if surgeons had such a relationship with industry. Respondents were also generally in favor of educational conferences for surgeons regardless of funding source. Disclosures of a surgeon-industry relationship, especially if it involves specific devices that may be used in their surgery, appears to be important to respondents. CONCLUSIONS: The vast majority of respondents in this study do not believe that the quality of their care will be diminished due to industry funding of educational events, for surgeon tuition, and/or travel expenses. The results of this study should help form the basis of policy and continued efforts at surgeon-industry COI management.

Health-related quality-of-life outcomes after thoracic (T1-T10) fractures.

BACKGROUND CONTEXT: The thoracic spine exhibits a unique response to trauma as the result of recognized anatomical and biomechanical differences. Despite this response, clinical studies often group thoracic fractures (T1-T10) with more caudal thoracolumbar injuries. Subsequently, there is a paucity of literature on the functional outcomes of this distinct group of injuries. PURPOSE: To describe and identify predictors of health-related quality-of-life outcomes and re-employment status in patients with thoracic fractures who present to a spine injury tertiary referral center. STUDY DESIGN: An ambispective cohort study with cross-sectional outcome assessment. PATIENT SAMPLE: A prospectively collected fully relational spine database was searched to identify all adult (>16 years) patients treated with traumatic thoracic (T1-T10) fractures with and without neurologic deficits, treated between 1995 and 2008. OUTCOME MEASURES: The Short-Form-36, Oswestry Disability Index, and Prolo Economic Scale outcome instruments were completed at a minimum follow-up of 12 months. Preoperative and minimum 1-year postinjury X-rays were evaluated. METHOD: Univariate and multivariate regression analysis was used to identify predictors of outcomes from a range of demographic, injury, treatment, and radiographic variables. RESULTS: One hundred twenty-six patients, age 36±15 years (mean±SD), with 135 fractures were assessed at a mean follow-up of 6 years (range 1-15.5 years). Traffic accidents (45%) and translational injuries (54%) were the most common mechanism and dominant fracture pattern, respectively. Neurologic deficits were frequent-53% had complete (American Spinal Injury Association impairment scale [AIS] A) spinal cord deficits on admission. Operative management was performed in 78%. Patients who sustain thoracic fractures, but escaped significant neurologic injury (AIS D or E on admission) had SF-36 scores that did not differ significantly from population norms at a mean follow-up of 6 years. Eighty-eight percent of this cohort was re-employed. Interestingly, Oswestry Disability Index scores remained inferior to healthy subjects. In contrast, SF-36 scores in those with more profound neurologic deficits at presentation (AIS A, B, or C) remained inferior to normative data. Fifty-seven percent were re-employed, 25% in their previous job type. Using multiple regression analysis, we found that comorbidity status (measured by the Charlson Comorbidity index) was the only independent predictor of SF-36 scores. Neurologic impairment (AIS) and adverse events were independent predictors of the SF-36 physical functioning subscale. Sagittal alignment and number of fused levels were not independent predictors. CONCLUSIONS: At a mean follow-up of 6 years, patients who presented with thoracic fractures and AIS D or E neurologic status recovered a general health status not significantly inferior to population norms. Compared with other neurologic intact spinal injuries, patients with thoracic injuries have a favorable generic health-related quality-of-life prognosis. Inferior outcomes and re-employment prospects were noted in those with more significant neurologic deficits.

Feasibility of patient recruitment into clinical trials of experimental treatments for acute spinal cord injury.

Clinical trials of experimental neuroprotective and neuroregenerative therapies for acute spinal cord injury (SCI) typically require large numbers of patients to be enrolled. An important factor in designing such trials is the number of patients that can be realistically recruited at a given institution. The total number of patients with acute SCI treated at a neurotrauma centre is typically considered when such a site becomes a recruiting centre for a clinical trial. However, only a fraction of patients may be truly eligible due to the inclusion and exclusion criteria of the trial. This study was conducted to estimate the proportion of patients with acute SCI who would theoretically satisfy basic inclusion criteria for such a hypothetical clinical trial. Using a local prospective database, we reviewed 406 patients with acute traumatic SCI admitted between 2005 and 2009. 259 of 406 patients (64%) presented within 12 hours of injury, 53 patients (13%) between 12 hours and 24 hours, and 30 patients (7%) between 24 hours and 48 hours. Patients were assessed on admission using the American Spinal Injury Association Impairment Scale: category A, 39% of patients; B, 11%; C, 17%; and D, 28%. The number of patients who presented with injuries or other conditions that would likely exclude them from enrolment was 30%. Thus, of a total of 406 patients with SCI admitted over four years, the number who would have been eligible for an acute clinical trial was disappointingly small. This study is the first to quantify this challenging aspect of conducting acute SCI clinical trials, and provides guidance for those planning such initiatives.

Separation anxiety: Gates-Glidden drills can be hazardous to your health.

INTRODUCTION: Gates-Glidden drills are commonly used during endodontic therapy to aid in the development of straight-line access and coronal enlargement of the root canal. The drills come in various sizes and are typically used in a low-speed air-driven or electric handpiece. As a safety feature to aid in retrieval if separation of the drill occurs during use, Gates-Glidden drills are designed to separate near the hub of the drill to allow for easier retrieval. METHODS: This case report presents a potentially serious complication associated with the use of Gates-Glidden drills. RESULTS: A contaminated drill became embedded in the arm of an endodontic resident and required surgical removal. CONCLUSIONS: Proper office safety precautions can help prevent accidents that may result in serious injury.

Comparison of atherosclerotic plaque burden and composition between diabetic and non diabetic patients by non invasive CT angiography.

Type 2 diabetes mellitus (DM) is associated with a higher risk of cardiovascular disease and atherosclerotic burden. However little data exists in regards to plaque distribution and plaque composition in these patients. To assess for differences in the coronary plaques burden and composition among symptomatic patients with and without type 2 DM using multidetector computed tomography angiography (MDCTA). The 416 symptomatic patients (64% males, mean age: 61 +/- 13 years) with 61 (15%) reporting type 2 DM, who underwent contrast-enhanced MDCTA were studied. Enrolled patients had an intermediate to high pre-test probability of obstructive coronary artery disease. Multivariate analysis was used to correct for differences in age and gender. Patients with type 2 DM were more likely to have significant stenosis >or=70% in at least one coronary segments (33% in type 2 DM vs. 18% in non diabetic, P = 0.013), whereas 11% of both type 2 DM and non diabetics had stenosis of 50-70% (P = NS). Also type 2 DM patients had a higher number of coronary segments with mixed plaques compared to nondiabetic patients (1.67 +/- 2.01 vs. 1.23 +/- 1.61, P = 0.05), whereas no such differences were observed for non-calcified or calcified plaques. Nearly half (43%) of type 2 DM had coronary artery calcium scores (CACS) >or=400 vs. 29% in non diabetic patients (P = 0.03). Patients with type 2 DM tend to have atherosclerotic plaques which are more likely to be mixed in nature. Future studies need to elucidate the prognostic value of differences in plaque characteristics observed according to type 2 diabetic status.

Calcium phosphate microcrystal deposition in the human intervertebral disc.

A variety of crystals have been identified in both normal and pathological connective tissues. Calcium phosphate 'cuboidal' microcrystal deposition has been found, using transmission electron microscopy (TEM), in femoral articular cartilage, where they are distributed as a band 5-50 microm beneath the articular surface. These cuboid microcrystals have been identified as magnesium whitlockite. Our objective was to investigate their presence in the human intervertebral disc. In this study, two degenerate and 15 scoliotic discs were examined using light microscopy and TEM techniques to determine the presence of calcium phosphate crystals. Calcium pyrophosphate dihydrate (CPPD) deposition was identified in one degenerate disc specimen. Using TEM and electron probe analysis, cuboid microcrystals were identified in the annulus fibrosus and nucleus pulposus of both degenerate specimens, but not in the discs from young scoliotic patients. Cuboid microcrystal deposition was found predominantly around cells, which were mainly necrotic, with some association with extracellular lipidic/membranous debris. This is the first TEM report of whitlockite in the intervertebral disc. In one specimen coexistence of cuboid and CPPD crystal deposition was found.