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The use of additive manufacturing in medical applications has become more prevalent over the last decade. Studies have proved that reconstruction plates with a mesh structure enhance the biocompatibility and bone-ingrowth formation. However, limited studies have been reported in the customization and in vivo clinical assessment of mesh implants. The purpose of this study was to investigate the surgical treatment and implant fitting accuracy using three different reconstruction plates. Fifteen goats were divided into one control and three experimental groups (Groups 1, 2, and 3) with five in each group. An experimental segmental defect was created on these animals and was adopted with customized electron beam melting reconstruction titanium plates with mesh in Group 1 and without mesh in Group 2 and commercial reconstruction plate in Group 3. All the animals were subjected to radiographic analysis before and after surgery. The subjected animals were sacrificed after 3 months and the electron beam melting reconstruction plates were compared with the commercial plate based on clinical and histology analysis and implant fitting accuracy. Both the electron beam melting reconstruction plates (with mesh and without mesh) and commercial plates survived the three months post-operation, revealing good wound-healing with new bone formation and without any foreign-body reaction. The electron beam melting reconstructed plate with mesh (Group 1) was found to have a better implant fitting when compared to the other two groups. The average discrepancy between Groups 2 and 3 was not significant. Certainly, the commercial plate (Group 3) was found to have the least accuracy as compared to other electron beam melting reconstruction plates (Group 1 and Group 2). Custom design electron beam melting fabricated reconstruction plates possessed better functionality, aesthetic outcome, and long-term biocompatibility when compared to commercial plates. Animal results indicated that the electron beam melting plates with mesh (Group 1) were superior in comparison to the other two groups due to its ability to provide better bone-in-growth and osseointegration on its porous microstructure.

Background: United States pharmacies repackage medications into multi-dose vials, enabling customized dosing for prescription drugs. Investment in infrastructure has made this the predominant approach to packaging for US prescriptions. Although recent changes to labeling now discourage the use of auxiliary labels (small stickers highlighting information germane to the safe and effective use), they are still allowed by USP, provided their use comes from an evidence-based perspective. Objectives: Evaluate how ‘interactive,’ placements of auxiliary labels (placement requiring physical manipulation of the warning to accomplish a task (e.g. opening)) garner attention as compared to those placed vertically or horizontally. Methods: Ninety-six participants were eye tracked while opening three prescription vials (each with an auxiliary warning label with a different placement: vertical, horizontal and interactive). Recall and recognition were tested subsequently. Linear mixed models were used to analyze the continuous variables while the binary response variables were analyzed using generalized linear mixed models. The effect of auxiliary labels was fitted as a fixed effect and the subject-to-subject variation was considered as a random effect in the model. Participants’ age, health literacy and sex were added to the models if their effect was statistically significant at alpha=0.05. Results: The placement of the warnings significantly impacted the time spent viewing the information they contained at alpha=0.05; people spent significantly longer on interactive placements (0.96; SD 0.13 seconds) than either, horizontal placements (0.27; SD 0.037 seconds) or those placed vertically (0.18 seconds; SD 0.035). Participants were equally as likely to see information presented in an interactive placement (90%; SD 3.8) or horizontal placement (78%; SD 05.5) but less likely to view warnings placed vertically (60%; SD 6.9). Free recall responses also supported the use of interactive placement (62%; SD 6.8 recall) as compared to horizontal placements which were 29%; SD 3.0 and 20%; SD 6.0 for vertical placements. Conclusions: Data provides evidence which suggests that interactive and horizontal placements out-perform auxiliary labels placed vertically on prescription vials with regard to garnering patient attention.

The health care system in Papua New Guinea is fragile, and surveillance systems infrequently meet international standards. To strengthen outbreak identification, health authorities piloted a mobile phone–based syndromic surveillance system and used established frameworks to evaluate whether the system was meeting objectives. Stakeholder experience was investigated by using standardized questionnaires and focus groups. Nine sites reported data that included 7 outbreaks and 92 cases of acute watery diarrhea. The new system was more timely (2.4 vs. 84 days), complete (70% vs. 40%), and sensitive (95% vs. 26%) than existing systems. The system was simple, stable, useful, and acceptable; however, feedback and subnational involvement were weak. A simple syndromic surveillance system implemented in a fragile state enabled more timely, complete, and sensitive data reporting for disease risk assessment. Feedback and provincial involvement require improvement. Use of mobile phone technology might improve the timeliness and efficiency of public health surveillance.

The centromere, on which kinetochore proteins assemble, ensures precise chromosome segregation. Centromeres are largely specified by the histone H3 variant CENP-A (also known as Cse4 in yeasts). Structurally, centromere DNA sequences are highly diverse in nature. However, the evolutionary consequence of these structural diversities on de novo CENP-A chromatin formation remains elusive. Here, we report the identification of centromeres, as the binding sites of four evolutionarily conserved kinetochore proteins, in the human pathogenic budding yeast Candida tropicalis. Each of the seven centromeres comprises a 2 to 5 kb non-repetitive mid core flanked by 2 to 5 kb inverted repeats. The repeat-associated centromeres of C. tropicalis all share a high degree of sequence conservation with each other and are strikingly diverged from the unique and mostly non-repetitive centromeres of related Candida species--Candida albicans, Candida dubliniensis, and Candida lusitaniae. Using a plasmid-based assay, we further demonstrate that pericentric inverted repeats and the underlying DNA sequence provide a structural determinant in CENP-A recruitment in C. tropicalis, as opposed to epigenetically regulated CENP-A loading at centromeres in C. albicans. Thus, the centromere structure and its influence on de novo CENP-A recruitment has been significantly rewired in closely related Candida species. Strikingly, the centromere structural properties along with role of pericentric repeats in de novo CENP-A loading in C. tropicalis are more reminiscent to those of the distantly related fission yeast Schizosaccharomyces pombe. Taken together, we demonstrate, for the first time, fission yeast-like repeat-associated centromeres in an ascomycetous budding yeast.

OBJECTIVES: This study aimed to evaluate the role of nonsurgical periodontal therapy in improving glycemic control among type 2 diabetes mellitus (T2DM) patients. MATERIALS AND METHODS: Adult T2DM patients with mild-to-moderate periodontal disease, reporting to a tertiary care diabetes center in South India, from January to June 2014, were enrolled in the study. Medical management of T2DM along with diet and physical exercise was an inclusion criterion. Patients with factors affecting periodontal health and an inability to follow-up were excluded from the study. All patients underwent nonsurgical periodontal therapy (scaling, root planing, and irrigation of chlorhexidine [0.12%]). Periodontal status and glycated hemoglobin A1c (HbA1c) were assessed preoperatively and 6 months posttreatment. Dental status, diabetic history, and demographic characteristics were recorded to evaluate confounding roles. RESULTS: A total of 266 T2DM patients (91 females/175 males; mean age 47.65 ± 5.93 years/range 25–55 years), fulfilling the inclusion criteria, were enrolled. The mean pre- and post-treatment HbA1c levels were respectively, 8.44 ± 1.87 and 7.98 ± 1.81, with a mean reduction of 0.46 ± 0.26 (P < 0.001). Significant HbA1c reduction (P < 0.001) was observed in patients with good pretreatment glycemic control (0.54 ± 0.26; 7.9%), regular follow-up (0.51 ± 0.28; 6.2%), and good oral hygiene (0.60 ± 0.49; 8.0%). CONCLUSION: Nonsurgical periodontal therapy is associated with significant HbA1c reduction among T2DM patients with mild-to-moderate periodontitis after a 6-month follow-up period.

Metabolic pathways play a vital yet poorly understood role in embryogenesis. In this issue of Developmental Cell , Bulusu et al. (2017) and Oginuma et al. (2017) provide insights into the intricate relationship between metabolism and morphogenesis, showing that glycolysis facilitates body elongation and balances neural and mesodermal differentiation. [ABSTRACT FROM AUTHOR]

Many developmental processes break left–right (LR) symmetry with a consistent handedness. LR asymmetry emerges early in development, and in many species the primary determinant of this asymmetry has been linked to the cytoskeleton. However, the nature of the underlying chirally asymmetric cytoskeletal processes has remained elusive. In this study, we combine thin-film active chiral fluid theory with experimental analysis of the C. elegans embryo to show that the actomyosin cortex generates active chiral torques to facilitate chiral symmetry breaking. Active torques drive chiral counter-rotating cortical flow in the zygote, depend on myosin activity, and can be altered through mild changes in Rho signaling. Notably, they also execute the chiral skew event at the 4-cell stage to establish the C. elegans LR body axis. Taken together, our results uncover a novel, large-scale physical activity of the actomyosin cytoskeleton that provides a fundamental mechanism for chiral morphogenesis in development.

β-Lactamases are the major reason β-lactam resistance is seen in Gram-negative bacteria. To combat this resistance mechanism, β-lactamase inhibitors are currently being developed. Presently, there are only three that are in clinical use (clavulanate, sulbactam and tazobactam). In order to address this important medical need, we explored a new inhibition strategy that takes advantage of a long-lived inhibitory trans-enamine intermediate. SA2-13 was previously synthesized and shown to have a lower k(react) than tazobactam. We investigated here the importance of the carboxyl linker length and composition by synthesizing three analogs of SA2-13 (PSR-4-157, PSR-4-155, and PSR-3-226). All SA2-13 analogs yielded higher turnover numbers and k(react) compared to SA2-13. We next demonstrated using protein crystallography that increasing the linker length by one carbon allowed for better capture of a trans-enamine intermediate; in contrast, this trans-enamine intermediate did not occur when the C2 linker length was decreased by one carbon. If the linker was altered by both shortening it and changing the carboxyl moiety into a neutral amide moiety, the stable trans-enamine intermediate in wt SHV-1 did not form; this intermediate could only be observed when a deacylation deficient E166A variant was studied. We subsequently studied SA2-13 against a relatively recently discovered inhibitor-resistant (IR) variant of SHV-1, SHV K234R. Despite the alteration in the mechanism of resistance due to the K→R change in this variant, SA2-13 was effective at inhibiting this IR enzyme and formed a trans-enamine inhibitory intermediate similar to the intermediate seen in the wt SHV-1 structure. Taken together, our data reveals that the C2 side chain linker length and composition profoundly affect the formation of the trans-enamine intermediate of penam sulfones. We also show that the design of SA2-13 derivatives offers promise against IR SHV β-lactamases that possess the K234R substitution.

An efficient terrain generation algorithm is developed, based on constrained conforming Delaunay triangulation. The density of triangulation in different regions of a terrain is determined by its flatness, as seen from a height map, and a control map. Tracks and other objects found in a game world can be applied over the terrain using the “stenciling” and “stitching” algorithms. Using user controlled parameters, varying levels of detail can be preserved when applying these objects over the terrain as well. The algorithms have been incorporated into 3dsMax as plugins, and the experimental results demonstrate the usefulness and efficiency of the developed algorithms.

Oil spills in maritime areas pose a serious environmental risk, wreaking havoc on marine ecosystems, coastal habitats, and local residents. An accurate and timely evaluation of oil spill occurrences and extent is critical for effective pollution control and mitigation. In this study, we present a novel and cutting-edge approach for analyzing oil-spilled images using Deep Attention Transformer Nets (DATN) with Collective Intelligence (CI), with the goal of reducing pollution in the marine environment. This method takes advantage of deep learning capability, notably the incorporation of transformer-based attention processes, to improve the identification and measurement of oil spills in satellite and aerial images. The DATN model is intended to learn complicated features from images automatically, capturing complex patterns associated with oil spills and their surrounding context. The model chooses focus on key regions and add spatial links by using attention mechanisms, allowing for a more comprehensive understanding of the environmental influence. We thoroughly test DATN performance using a variety of datasets encompassing various oil spill scenarios and environmental circumstances. The results show that DATN surpasses standard approaches and other deep learning models in recognizing oil spill regions, with excellent accuracy, precision, and recall rates. Furthermore, the model has strong generalization capabilities across a wide range of image sources and situations. [ABSTRACT FROM AUTHOR]

Background Aspiration of oropharyngeal or gastric contents into the lower airways can cause a number of syndromes including chemical and bacterial pneumonia, although the pathophysiology of each entity is different. Data from Dr Foster's Guide and our local coding department revealed a high incidence and mortality from aspiration pneumonia alerting us to study those patients. Methods Retrospective analysis of 53 patients coded as aspiration pneumonia from February 2010 to March 2011. Analysis of presentation, investigations, management, pre-disposing factors and outcome was undertaken. Results Average Age 78, M/F ratio (1:1). Out of 53 coded as aspiration pneumonia, 2 were re-coded to an alternative diagnosis. Out of 51 patients, 36 died (71%) and 15 survived but 17/51 (23%) had chest x-rays which were not suggestive of aspiration pneumonia. Of the 36 patients that died, 67% showed positive x-ray changes, while the 15 survivors had 80% x-rays suggesting pneumonia. Abstract S64 table 1 shows the list of clinical presentations and potential risk factors. On average each patient had 4 out of the 7 clinical features positive. 23/51 (45%) had either a basic swallow or SALT assessment of whom only 2/23 (9%) passed. 0/51 (0%) proceeded to mechanical ventilation. 51/51 (100%) had oxygen, intravenous fluids and antibiotics. Conclusion Aspiration pneumonia has a high mortality, particular in those with a history of aspiration living in residential or nursing facilities. 23% of patients with a good clinical history of aspiration did not show x-ray changes to suggest pneumonia. It may suggest a difference in the pathophysiology of lung injury in these patients who aspirate acidic gastric contents causing a chemical injury without x-ray changes of pneumonia. Although the treatment at present is no different, research needs to be incorporated into guidelines to diagnose, prevent and treat the different types of aspiration. [ABSTRACT FROM AUTHOR]

Presence of cold agglutinins in any cardiac surgical patient increases the likelihood of haemolysis. Prevention is more important and a normothermic cardiopulmonary bypass and warm myocardial protection are well established means for preventing intravascular haemolysis in these patients. If hypothermia cannot be avoided, other special techniques like total wash-out method can be used. With increasing awareness of its presence, the morbidity should be kept at minimum. [ABSTRACT FROM AUTHOR]

Introduction: Breast cancer is a heterogeneous disease, comprising numerous distinct entities that have different biological features and clinical behaviour. There are many biomarkers that are related to the progression and therapeutic response of invasive breast cancer. One emerging biomarker is Cyclin D1 which is a key cell cycle regulatory protein, encoded by the gene, CCND1 or PRAD1, positioned on chromosome 11q13. Thus, the present study is an attempt to analyse immunohistochemical expression of Cyclin D1 in breast carcinoma and correlate it with other known histopathological prognostic markers. Materials and Methods: A study of forty breast carcinoma patients carried out in the Dept. of Pathology during 2019-2022. Immunohistochemical staining of Cyclin D1 was performed. The intensity of Cyclin D1 staining will be scored on a scale from 0 to 3 and results were tabulated. Data was entered in MS Excel and analyzed using Pearson's Chi-square test and fisher exact test. A P value <0.05 was considered as statistically significant. Results: Statistically significant results were obtained with Cyclin D1 and grade of the tumor (p value 0.04). However, correlation of Cyclin D1 with size, lymphnode status and lymphovascular invasion was not statistically significant. Conclusion: Our study confirms the strong association between Cyclin D1 and grade of the tumour which is one of the oldest and the strongest prognostic marker known in breast carcinoma. Cyclin D1 expression appears to be a good independent marker in breast cancer and can be included in the pool of prognostic markers like tumor size, nodal status, histopathological grade. [ABSTRACT FROM AUTHOR]

Background We have previously shown that raised p-S6K levels correlate with resistance to chemotherapy in ovarian cancer. We hypothesised that inhibiting p-S6K signalling with the dual m-TORC1/2 inhibitor in patients receiving weekly paclitaxel could improve outcomes in such patients. Patients and methods In dose escalation, weekly paclitaxel (80 mg/m2) was given 6/7 weeks in combination with two intermittent schedules of vistusertib (dosing starting on the day of paclitaxel): schedule A, vistusertib dosed bd for 3 consecutive days per week (3/7 days) and schedule B, vistusertib dosed bd for 2 consecutive days per week (2/7 days). After establishing a recommended phase II dose (RP2D), expansion cohorts in high-grade serous ovarian cancer (HGSOC) and squamous non-small-cell lung cancer (sqNSCLC) were explored in 25 and 40 patients, respectively. Results The dose-escalation arms comprised 22 patients with advanced solid tumours. The dose-limiting toxicities were fatigue and mucositis in schedule A and rash in schedule B. On the basis of toxicity and pharmacokinetic (PK) and pharmacodynamic (PD) evaluations, the RP2D was established as 80 mg/m2 paclitaxel with 50 mg vistusertib bd 3/7 days for 6/7 weeks. In the HGSOC expansion, RECIST and GCIG CA125 response rates were 13/25 (52%) and 16/25 (64%), respectively, with median progression-free survival (mPFS) of 5.8 months (95% CI: 3.28–18.54). The RP2D was not well tolerated in the SqNSCLC expansion, but toxicities were manageable after the daily vistusertib dose was reduced to 25 mg bd for the following 23 patients. The RECIST response rate in this group was 8/23 (35%), and the mPFS was 5.8 months (95% CI: 2.76–21.25). Discussion In this phase I trial, we report a highly active and well-tolerated combination of vistusertib, administered as an intermittent schedule with weekly paclitaxel, in patients with HGSOC and SqNSCLC. Clinical trial registration ClinicialTrials.gov identifier: CNCT02193633 [ABSTRACT FROM AUTHOR]

While dual fuel low temperature combustion (LTC) has been studied before, a detailed second law analysis of dual fuel LTC is not yet available in the open literature. To address this gap, a previously validated, closed-cycle, multi-zone, simulation of diesel-natural gas dual fuel LTC was used to perform a second law analysis. For the present study, a 2.4-l single-cylinder research engine operating at a nominal load of 6 bar BMEP and 1700 rpm was used. Zone-wise thermodynamic irreversibilities as well as total cumulative entropy generated and lost available work over the closed cycle were quantified. Subsequently, two convenient second-law parameters were defined: (1) the “lost available indicated mean effective pressure” (LAIMEP), which can be interpreted as an engine-size-normalized measure of available work that is lost due to thermodynamic irreversibilities (analogous to the relationship between indicated mean effective pressure and indicated work); (2) fuel conversion irreversibility (FCI), which is defined as the ratio of lost available work to total fuel chemical energy input. Finally, parametric studies were performed to quantify the effects of diesel start of injection, intake manifold temperature, and intake boost pressure on LAIMEP and FCI. The results show that significant entropy generation occurred in the flame zone (52–61 percent) and the burned zone (31–39 percent) while packets account for less than 6 percent of the overall irreversibilities. Parametric studies showed LAIMEPs in the range of 645–768 kPa and FCIs in the range of 32.8–39.2 percent at different engine operating conditions. Although the present study focused on dual fuel LTC, the conceptual definitions of LAIMEP and FCI are generally applicable for comparing the thermodynamic irreversibilities of IC engines of any size and operating on any combustion strategy. [ABSTRACT FROM AUTHOR]

Molecular motors, highly efficient biological nanomachines, hold the potential to be employed for a wide range of nanotechnological applications. Toward this end, kinesin, dynein, or myosin motor proteins are commonly surface-immobilized within engineered environments in order to transport cargo attached to cytoskeletal filaments. Being able to flexibly control the direction of filament motion, and in particular on planar, non-topographical surfaces, has, however, remained challenging. Here, we demonstrate the applicability of a UV-laser-based ablation technique to programmably generate highly localized patterns of functional kinesin-1 motors with different shapes and sizes on PLL-g-PEG-coated polystyrene surfaces. Straight and curved motor tracks with widths of less than 500 nm could be generated in a highly reproducible manner and proved to reliably guide gliding microtubules. Though dependent on track curvature, the characteristic travel lengths of the microtubules on the tracks significantly exceeded earlier predictions. Moreover, we experimentally verified the performance of complex kinesin-1 patterns, recently designed by evolutionary algorithms for controlling the global directionality of microtubule motion on large-area substrates. [ABSTRACT FROM AUTHOR]

The present experimental study evaluates laser peening for suppressing intergranular corrosion (IGC) susceptibility of sensitised 304 stainless steel. Under the given experimental conditions, an increase in the number of laser peening treatments of sensitised 304 stainless steel specimen brought about progressive reduction in its susceptibility to IGC. Triple laser peening of sensitised stainless steel specimen introduced remarkable reduction in its IGC susceptibility. The results of the study suggest that breakage of inter-granular network of chromium carbides/chromium-depleted regions through plastic deformation, imposed by multiple laser peening treatment, was responsible for causing significant suppression in IGC susceptibility of sensitised 304 stainless steel specimens. [ABSTRACT FROM AUTHOR]