Full-Body Radiographic Analysis of Postoperative Deviations From Age-Adjusted Alignment Goals in Adult Spinal Deformity Correction and Related Compensatory Recruitment.

Background: Full-body stereographs for adult spinal deformity (ASD) have enhanced global deformity and lower-limb compensation associations. The advent of age-adjusted goals for classic ASD parameters (sagittal vertical axis, pelvic tilt, spino-pelvic mismatch [PI-LL]) has enabled individualized evaluation of successful versus failed realignment, though these remain to be radiographically assessed postoperatively. This study analyzes pre- and postoperative sagittal alignment to quantify patient-specific correction against age-adjusted goals, and presents differences in compensation in patients whose postoperative profile deviates from targets. Methods: Single-center retrospective review of ASD patients ≥ 18 years with biplanar full-body stereographic x-rays. Inclusion: ≥ 4 levels fused, complete baseline and early (≤ 6-month) follow-up imaging. Correction groups generated at postoperative visit for actual alignment compared to age-adjusted ideal values for pelvic tilt, PI-LL, and sagittal vertical axis derived from clinically relevant formulas. Patients that matched exact ± 10-year threshold for age-adjusted targets were compared to unmatched cases (undercorrected or overcorrected). Comparison of spinal alignment and compensatory mechanisms (thoracic kyphosis, hip extension, knee flexion, ankle flexion, pelvic shift) across correction groups were performed with ANOVA and paired Results: The sagittal vertical axis, pelvic tilt, and PI-LL of 122 patients improved at early postoperative visits ( Conclusions: Global alignment cohort improvements were observed, and when comparing actual to age-adjusted alignment, undercorrections recruited pelvic and lower-limb flexion to compensate. Level of Evidence: 3

Design and development of a complex narrative intervention delivered by text messages to reduce binge drinking among socially disadvantaged men

Background: Socially disadvantaged men are at high risk of suffering from alcohol-related harm. Disadvantaged groups are less likely to engage with health promotion. There is a need for interventions that reach large numbers at low cost and which promote high levels of engagement with the behaviour change process. The aim of this study was to design a theoretically and empirically based text message intervention to reduce binge drinking by socially disadvantaged men. Results: Following MRC guidance, the intervention was developed in four stages. Stage 1 developed a detailed behaviour change strategy based on existing literature and theory from several areas. These included the psychological theory that would underpin the intervention, alcohol brief interventions, text message interventions, effective behaviour change techniques, narratives in behaviour change interventions and communication theory. In addition, formative research was carried out. A logic model was developed to depict the pathways between intervention inputs, processes and outcomes for behaviour change. Stage 2 created a narrative which illustrated and modelled key steps in the strategy. Stage 3 rendered the intervention into a series of text messages and ensured that appropriate behavioural change techniques were incorporated. Stage 4 revised the messages to ensure comprehensive coverage of the behaviour change strategy and coherence of the narrative. It also piloted the intervention and made final revisions to it. Conclusions: The structured, systematic approach to design created a narrative intervention which had a strong theoretical and empirical basis. The use of a narrative helped make the intervention realistic and allowed key behaviour change techniques to be modelled by characters. The narrative was intended to promote engagement with the intervention. The intervention was rendered into a series of short text messages, and subsequent piloting showed they were acceptable in the target group. Delivery of an intervention by text message offers a low-cost, low-demand method that can reach large numbers of people. This approach provides a framework for the design of behaviour change interventions which could be used for interventions to tackle other health behaviours

Crizotinib in patients with tumors harboring ALK or ROS1 rearrangements in the NCI-MATCH trial.

The NCI-MATCH was designed to characterize the efficacy of targeted therapies in histology-agnostic driver mutation-positive malignancies. Sub-protocols F and G were developed to evaluate the role of crizotinib in rare tumors that harbored either ALK or ROS1 rearrangements. Patients with malignancies that progressed following at least one prior systemic therapy were accrued to the NCI-MATCH for molecular profiling, and those with actionable ALK or ROS1 rearrangements were offered participation in sub-protocols F or G, respectively. There were five patients who enrolled on Arm F (ALK) and four patients on Arm G (ROS1). Few grade 3 or 4 toxicities were noted, including liver test abnormalities, and acute kidney injury. For sub-protocol F (ALK), the response rate was 50% (90% CI 9.8-90.2%) with one complete response among the 4 eligible patients. The median PFS was 3.8 months, and median OS was 4.3 months. For sub-protocol G (ROS1) the response rate was 25% (90% CI 1.3-75.1%). The median PFS was 4.3 months, and median OS 6.2 months. Data from 3 commercial vendors showed that the prevalence of ALK and ROS1 rearrangements in histologies other than non-small cell lung cancer and lymphoma was rare (0.1% and 0.4% respectively). We observed responses to crizotinib which met the primary endpoint for ALK fusions, albeit in a small number of patients. Despite the limited accrual, some of the patients with these oncogenic fusions can respond to crizotinib which may have a therapeutic role in this setting

Prediction of Protein Domain with mRMR Feature Selection and Analysis

The domains are the structural and functional units of proteins. With the avalanche of protein sequences generated in the postgenomic age, it is highly desired to develop effective methods for predicting the protein domains according to the sequences information alone, so as to facilitate the structure prediction of proteins and speed up their functional annotation. However, although many efforts have been made in this regard, prediction of protein domains from the sequence information still remains a challenging and elusive problem. Here, a new method was developed by combing the techniques of RF (random forest), mRMR (maximum relevance minimum redundancy), and IFS (incremental feature selection), as well as by incorporating the features of physicochemical and biochemical properties, sequence conservation, residual disorder, secondary structure, and solvent accessibility. The overall success rate achieved by the new method on an independent dataset was around 73%, which was about 28–40% higher than those by the existing method on the same benchmark dataset. Furthermore, it was revealed by an in-depth analysis that the features of evolution, codon diversity, electrostatic charge, and disorder played more important roles than the others in predicting protein domains, quite consistent with experimental observations. It is anticipated that the new method may become a high-throughput tool in annotating protein domains, or may, at the very least, play a complementary role to the existing domain prediction methods, and that the findings about the key features with high impacts to the domain prediction might provide useful insights or clues for further experimental investigations in this area. Finally, it has not escaped our notice that the current approach can also be utilized to study protein signal peptides, B-cell epitopes, HIV protease cleavage sites, among many other important topics in protein science and biomedicine

Effects of Fluoride on Rachitic Rats

Both vitamin D-deficient diet and fluoride intake affect calcified tissues and parathyroids in growing rats. Studies were designed to investigate effects of low fluoride intake on rachitic rat femoral bones and parathyroids. Holtzman rats placed on rachitic diet were given distilled water to which 4 , 8, and 20 ppm fluoride a s NaF was added. Control groups consisted of rats on normal laboratory diet and tap water, normal diet and fluoride-treated water, and rachitic diet and tap water. Tetracycline was administered to all groups 5 and 15 days before sacrifice. Animals were provided with these diets and appropriate waters ad libitum until sacrificed after 4 weeks treatment. Parathyroids were removed and prepared for routine paraffin sectioning. Femurs were removed and prepared for routine frozen and paraffin sectioning. Naphthol AS-BI phosphoric acid was used a s substrate for Burstone\u27s method of acid and alkaline phosphatase activity. Bone and parathyroid sections were stained with H & E and PAS. Compared with rachitic control rats , f luoride-treated rachitic rats showed: (1) a slight decrease in body growth rate, and femur weight and length: (2) a slight increase in diaphysial cortical thickness: (3) no change in either phosphatase activity: (4) a decrease in distance between periosteal tetracycline labels: (5) no apparent histological change in parathyroids: and (6) no marked change in size or numbers of femoral diaphysial resorption spaces. These observations indicate that at these dosages, fluoride: (1) caused delayed rate of periosteal bone mineralization measured by tetracycline labels. As the fluoride dosage increased, distances between labels markedly decreased. (2) had no apparent effect on either phosphatase enzyme activity. Activity was seen at periosteal and endosteal surfaces, and in cortical resorption spaces. Activity increased over normal controls, but was similar to those of rachitic controls

Effects of Fluoride on Rachitic Rats

Both vitamin D-deficient diet and fluoride intake affect calcified tissues and parathyroids in growing rats. Studies were designed to investigate effects of low fluoride intake on rachitic rat femoral bones and parathyroids. Holtzman rats placed on rachitic diet were given distilled water to which 4 , 8, and 20 ppm fluoride a s NaF was added. Control groups consisted of rats on normal laboratory diet and tap water, normal diet and fluoride-treated water, and rachitic diet and tap water. Tetracycline was administered to all groups 5 and 15 days before sacrifice. Animals were provided with these diets and appropriate waters ad libitum until sacrificed after 4 weeks treatment. Parathyroids were removed and prepared for routine paraffin sectioning. Femurs were removed and prepared for routine frozen and paraffin sectioning. Naphthol AS-BI phosphoric acid was used a s substrate for Burstone\u27s method of acid and alkaline phosphatase activity. Bone and parathyroid sections were stained with H & E and PAS. Compared with rachitic control rats , f luoride-treated rachitic rats showed: (1) a slight decrease in body growth rate, and femur weight and length: (2) a slight increase in diaphysial cortical thickness: (3) no change in either phosphatase activity: (4) a decrease in distance between periosteal tetracycline labels: (5) no apparent histological change in parathyroids: and (6) no marked change in size or numbers of femoral diaphysial resorption spaces. These observations indicate that at these dosages, fluoride: (1) caused delayed rate of periosteal bone mineralization measured by tetracycline labels. As the fluoride dosage increased, distances between labels markedly decreased. (2) had no apparent effect on either phosphatase enzyme activity. Activity was seen at periosteal and endosteal surfaces, and in cortical resorption spaces. Activity increased over normal controls, but was similar to those of rachitic controls