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The article presents a study which investigated how exposure to geriatric medicine before medical school through Hospital Elder Life Program (HELP) impacts students' interest and attitudes toward geriatrics. Topics discussed include self-assessment of perceptions of the field of geriatrics by respondents before and after participating in the HELP program, students' retrospective assessments about themselves before the program, and limitation of this type of assessment.

Introduction: Resuscitative thoracotomy (RT) is an emergent procedure to gain access to the thoracic cavity to control hemorrhage and other life-threatening injuries. Data predicting survival is variable. This review aims to highlight key predictors of survival and mortality following RT. Methods: The EMBASE database was searched using the following terms: [exp. Thoracotomy] AND [Trauma.mp] AND [exp. Survival OR exp. Mortality]. The search was limited to full-text articles in the English language and publications released up to February 27, 2022. Reference lists of included articles were reviewed to identify other studies meeting inclusion criteria. Results: Thirty-seven studies were included. Seventy-six outcome predictors were identified. Prehospital outcome predictors included prehospital vital signs, police transport, cardiopulmonary resuscitation, application of a cervical spine collar, and the number of total prehospital procedures performed. In-hospital variables associated with survival included traumatic cardiac arrest (TCA) in the emergency department (ED), initial ED vital signs and cardiac rhythm, Shock Index Pediatric Age-Adjusted score, location of RT, duration of RT, Focused Assessment with Sonography in Trauma findings, amount of blood products, and amount of administered fluids. Conclusions: Our study highlights the disparity of data regarding prehospital outcome predictors for trauma patients requiring RT. Most studies focus on injury-specific and in-hospital variables and do not explicitly look at the TCA population. Further work is needed to better define specific variables implicated in enhanced survival across different care settings and to inform management guidelines within these clinical areas. [ABSTRACT FROM AUTHOR]

Purpose: Necrotizing enterocolitis (NEC) is a severe intestinal disease primarily affecting premature infants, marked by impaired epithelial regeneration. Breastfed infants are less susceptible to NEC than formula-fed ones, and human milk oligosaccharides (HMO) found in breast milk have prebiotic properties that can protect against NEC. However, it is unclear how HMOs influence intestinal epithelium regeneration in relation to the gut microbiota. Methods: Broad-spectrum antibiotics were administered to pregnant dams to reduce the microbiota in offspring. NEC was induced through administration of hyperosmolar formula, lipopolysaccharide, and hypoxia from postnatal days (p) 5–9. Intestinal epithelial organoids were derived from p9 mice. HMOs were isolated from human donor breast milk and then solubilized in the formula for each feed or culture media for organoids. Results: HMOs did not alter the microbiota profile in the presence of a normal or reduced microbiota. In the reduced microbiota, HMO treatment decreased NEC intestinal injury, and increased proliferation and stem cell activity. Additionally, in the complete absence of the microbiota, HMOs stimulated intestinal organoid growth. Conclusion: This study demonstrates that HMOs promoted intestinal epithelial regeneration independent of the gut microbiota. These findings provide further insight into the various benefits HMOs may have in the protection against NEC. [ABSTRACT FROM AUTHOR]

Objectives: Physical examinations are essential for in-person patient visits but remain difficult to replicate during virtual encounters. This work aims to identify gaps in the current state of telemedicine-based physical assessments by surveying physical medicine and rehabilitation physicians who perform physical examinations. Design: A survey of 29 Likert-scale questions and five open-ended questions was distributed to practicing physical medicine and rehabilitation physicians. The Likert-scale questions covered remote physical assessment, access, perception/engagement, implementation/effectiveness, and administrative concerns. Results: Fifty-three participants completed the survey. More than 80% of respondents suggested that while telemedicine was universally well accepted, they could not effectively perform telemedicine-based physical assessments, especially the musculoskeletal and neurological components. Remote assessment of upper and lower limb strength, reflexes, and sensation were examples of key unmet needs. Responses to open-ended questions suggested that telemedicine-based physical assessments can reduce the burden of travel and increase adherence to follow-up visits, but complex technology setup can pose difficulty for older patients and patients with cognitive deficits. Conclusions: These findings suggest that current telemedicine technology is insufficient to meet physical medicine and rehabilitation physicians' telemedicine-based physical assessments needs. Despite high levels of provider and patient engagement with telemedicine, numerous deficits remain in performing musculoskeletal and neurological examinations. These results can inform future technology developments that address these identified telemedicine-based physical assessments gaps. [ABSTRACT FROM AUTHOR]

Background: Ulcerative colitis (UC) and Crohn's disease (CD) are chronic inflammatory bowel diseases (IBD) that affect women in their childbearing years. Early pregnancy flare-up negatively impacts obstetrical and perinatal outcomes, but the impact on infants is unclear.Aim: To determine whether active IBD disease activity is associated with adverse post-neonatal outcomes post-partum.Methods: This is a single-center cohort study of women with IBD who underwent serial monitoring of post-neonatal outcomes post-partum. Infant outcomes were collected via self-filled questionnaires, including perinatal outcomes, APGAR scores, infant weights, heights, feeding habits and comorbidities within the first year of life.Results: There was a total of 98 women with IBD and 78 live births throughout the study: 50 women were enrolled during trimester one alone and 49 were included into the current study. Among the 49 analyzed, 32 were in remission and 17 were in relapse during trimester one. Trimester one disease activity was associated with more adverse obstetrical outcomes including emergency C-sections and reduced 1-min APGAR scores. At follow-up, infants born to women with T1-flare had reduced weight-for-age Z scores and length-for-age Z scores up to 6 months of age.Conclusions: Active IBD during trimester one is correlated with adverse post-neonatal outcomes, particularly decreased infant weight and height up to 6 months of age. This suggests disease control in first trimester is essential for optimizing infant growth and post-neonatal outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Cutaneous squamous cell cancer is a form of skin cancer, which is typically found in older fair-skinned individuals with frequent sun exposure. Most patients present with limited disease and can be treated with a combination of surgery and/or radiation with favorable outcomes. A small percentage of patients present with more aggressive, widespread disease. Immunotherapy has dramatically improved outcomes and has become the preferred treatment option for these patients. In this review article, the rationale for using immunotherapy in patients with squamous cell skin cancer is discussed. A summary of the new treatment options currently being explored is also provided. Cutaneous squamous cell carcinoma (CSCC) is the second most common non-melanoma skin cancer. A majority of patients present with localized disease, but some can present with locally advanced or metastatic disease. Most of these advanced cases occur in the anatomical head and neck region and are associated with more aggressive disease, necessitating prompt and effective treatment. Prior to the emergence of immunotherapy, systemic treatment options were limited to platinum-based chemotherapy and salvaged with targeted epidermal growth factor therapy. These therapies were associated with poor efficacy and increased toxicity in an often frail, older population. Immunotherapy has dramatically improved outcomes in this patient population due to its favorable side effect profile, durable treatment response, and improved overall outcomes. In this review, an overview of the recent advances of immunotherapy in the management of CSCC in the anatomical head and neck region is provided, with a focus on advanced presentations. [ABSTRACT FROM AUTHOR]

Inflammatory bowel diseases (IBD), including Ulcerative Colitis (UC) and Crohn's disease (CD), are inflammatory conditions of the intestinal tract that affect women in their reproductive years. Pregnancy affects Th1- and Th2-cytokines, but how these changes occur during pregnancy in IBD is unclear. We performed a longitudinal profiling of serum cytokines in a cohort of 11 healthy pregnant women and 76 pregnant women with IBD from the first trimester of pregnancy to the first 12 months post-partum. Participants were monitored for biochemical disease activity (C-reactive protein [CRP] and fecal calprotectin [FCP]) and clinical activities. Maternal cytokines were measured using ELISA. We identified changes in Th1 and Th17 cytokines throughout pregnancy in healthy pregnant women. During pregnancy, maternal serum cytokine expressions were influenced by IBD, disease activity, and medications. Active UC was associated with an elevation in IL-21, whereas active CD was associated with elevated IFN-γ, IL-6, and IL-21. Interestingly, T1 serum cytokine levels of IL-22 (>0.624 pg/mL) and IL-6 (>0.648 pg/mL) were associated with worse IBD disease activity throughout pregnancy in women with UC and CD, respectively. This shows serum cytokines in pregnancy differ by IBD, disease activity, and medications. We show for the first time that T1 IL-22 and IL-6 correlate with IBD disease course throughout pregnancy. [ABSTRACT FROM AUTHOR]

The recognition of pain and the treatments used for it are vital for all practitioners. Many types of pain can be treated in a locoregional fashion, which has significant implications not just for any individual patient but for society as a whole. These treatments are most effective when performed in a minimally invasive, image-guided fashion. Interventional radiologists should play a central role in providing these lifestyle-limiting treatments. This article describes the medications most typically used for spinal and extra-axial treatments in the management of patients in pain. [ABSTRACT FROM AUTHOR]

Purpose: To improve the effectivity of patient-specific finite element analysis (FEA) to predict refractive power change (RPC) in rigid Ortho-K contact lens fitting. Novel eyelid boundary detection is introduced to the FEA model to better model the effects of the lid on lens performance, and stress and strain outcomes are investigated to identify the most effective FEA components to use in modelling. Methods: The current study utilises fully anonymised records of 249 eyes, 132 right eyes, and 117 left eyes from subjects aged 14.1 ± 4.0 years on average (range 9 to 38 years), which were selected for secondary analysis processing. A set of custom-built MATLAB codes was built to automate the process from reading Medmont E300 height and distance files to processing and displaying FEA stress and strain outcomes. Measurements from before and after contact lens wear were handled to obtain the corneal surface change in shape and power. Tangential refractive power maps were constructed from which changes in refractive power pre- and post-Ortho-K wear were determined as the refractive power change (RPC). A total of 249 patient-specific FEA with innovative eyelid boundary detection and 3D construction analyses were automatically built and run for every anterior eye and lens combination while the lens was located in its clinically detected position. Maps of four stress components: contact pressure, Mises stress, pressure, and maximum principal stress were created in addition to maximum principal logarithmic strain maps. Stress and strain components were compared to the clinical RPC maps using the two-dimensional (2D) normalised cross-correlation and structural similarity (SSIM) index measure. Results: On the one hand, the maximum principal logarithmic strain recorded the highest moderate 2D cross-correlation area of 8.6 ± 10.3%, and contact pressure recorded the lowest area of 6.6 ± 9%. Mises stress recorded the second highest moderate 2D cross-correlation area with 8.3 ± 10.4%. On the other hand, when the SSIM index was used to compare the areas that were most similar to the clinical RPC, maximum principal stress was the most similar, with an average strong similarity percentage area of 26.5 ± 3.3%, and contact pressure was the least strong similarity area of 10.3 ± 7.3%. Regarding the moderate similarity areas, all components were recorded at around 34.4% similarity area except the contact pressure, which was down to 32.7 ± 5.8%. Conclusions: FEA is an increasingly effective tool in being able to predict the refractive outcome of Ortho-K treatment. Its accuracy depends on identifying which clinical and modelling metrics contribute to the most accurate prediction of RPC with minimal ocular complications. In terms of clinical metrics, age, Intra-ocular pressure (IOP), central corneal thickness (CCT), surface topography, lens decentration and the 3D eyelid effect are all important for effective modelling. In terms of FEA components, maximum principal stress was found to be the best FEA barometer that can be used to predict the performance of Ortho-K lenses. In contrast, contact pressure provided the worst stress performance. In terms of strain, the maximum principal logarithmic strain was an effective strain barometer. [ABSTRACT FROM AUTHOR]

The use of multiparametric MRI has been hastened under expanding, novel indications for its use in the diagnostic and management pathway of men with prostate cancer. This has helped drive a large body of the literature describing its evolving role over the last decade. Despite this, prostate cancer remains the only solid organ malignancy routinely diagnosed with random sampling. Herein, we summarize the components of multiparametric MRI and interpretation, and present a critical review of the current literature supporting is use in prostate cancer detection, risk stratification, and management. [ABSTRACT FROM AUTHOR]

This article uses data gathered from a survey that probed the career orientations and values of more than 1,000 law students in Beijing, Hong Kong and Taipei to examine the legal professionalism of future lawyers being trained under different legal education systems in Greater China. Our findings suggest that these future lawyers have a "materialistic" career orientation, although those studying in a system whose legal education goal is to train professional lawyers are more inclined to pursue professional legal ideals, and those trained in a system that emphasizes legal ethics are more likely to pursue public interest issues. On the basis of the findings, we argue that legal education systems in Greater China, while different in their traditions, share the same need to strengthen legal professionalism by according greater emphasis to legal ethics in their respective law school curricula. [ABSTRACT FROM AUTHOR]

Purpose: Video assessment is an emerging tool for understanding surgical technique. Patient outcomes after robot-assisted radical prostatectomy (RARP) may be linked to technical aspects of the procedure. In an effort to refine surgical approaches and improve outcomes, we sought to understand technical variation for the key steps of RARP in a surgical collaborative. Methods: The Michigan Urological Surgery Improvement Collaborative (MUSIC) is a statewide quality improvement collaborative with the aim of improving prostate cancer care. MUSIC surgeons were invited to submit representative complete videos of nerve-sparing RARP for blinded analysis. We also analyzed peri-operative outcomes from these surgeons in the registry. Results: Surgical video data from 20 unique surgeons identified many variations in technique and time to complete different steps. Common to all surgeons was a transperitoneal approach and a running urethrovesical anastomosis. Prior to anastomosis, 25% surgeons undertook a posterior reconstruction and 30% employed urethral suspension. 65% surgeons approached the seminal vesicle anteriorly. For control of the dorsal vein complex, suture ligation was used in 60%, and vascular stapler was 15%. The majority (80%) of surgeons employed clips for managing pedicles. In examining patient outcomes for surgeons, peri-operative outcomes were not correlated with surgeon's operative time; however, surgeons with an EBL > 400 ml had significant difference among the five different techniques employed. Conclusions: Despite the worldwide popularity of RARP, the operation is still far from standardized. Correlating variation in technique with clinical outcomes may help provide objective data to support best practices with the goal to improve patient outcomes. [ABSTRACT FROM AUTHOR]

Methods that determine the relative purity of biopharmaceuticals represent the most widely used form of analysis for the pharmaceutical industry. The ability to rapidly assess method capability or the uncertainty of measurements under actual use conditions continues to present significant challenges. We have refined and applied the model of Uncertainty Based on Current Information to predict the precision of the purity measurements and compared the predicted precision to the measured variability for several different types of purity methods. The measured method variability was derived from the analysis of data sets ranging from hundreds to thousands of measurements for each different method type. The predicted precision was found to be in excellent agreement with the statistically obtained values with R2 = 0.94. This demonstration of concurrence between the predicted and actual precision provides an opportunity for streamlining laborious conventional (statically derived) assessment of method precision and leveraging the Uncertainty Based on Current Information model utilizing much smaller data sets or even a single experiment. [ABSTRACT FROM AUTHOR]

Objective: Rapid eye movement sleep behavior disorder (RBD) is a prodromal synucleinopathy, as >80% will eventually convert to overt synucleinopathy. We performed an in-depth analysis of the SNCA locus to identify RBD-specific risk variants.Methods: Full sequencing and genotyping of SNCA was performed in isolated/idiopathic RBD (iRBD, n = 1,076), Parkinson disease (PD, n = 1,013), dementia with Lewy bodies (DLB, n = 415), and control subjects (n = 6,155). The iRBD cases were diagnosed with RBD prior to neurodegeneration, although some have since converted. A replication cohort from 23andMe of PD patients with probable RBD (pRBD) was also analyzed (n = 1,782 cases; n = 131,250 controls). Adjusted logistic regression models and meta-analyses were performed. Effects on conversion rate were analyzed in 432 RBD patients with available data using Kaplan-Meier survival analysis.Results: A 5'-region SNCA variant (rs10005233) was associated with iRBD (odds ratio [OR] = 1.43, p = 1.1E-08), which was replicated in pRBD. This variant is in linkage disequilibrium (LD) with other 5' risk variants across the different synucleinopathies. An independent iRBD-specific suggestive association (rs11732740) was detected at the 3' of SNCA (OR = 1.32, p = 4.7E-04, not statistically significant after Bonferroni correction). Homozygous carriers of both iRBD-specific SNPs were at highly increased risk for iRBD (OR = 5.74, p = 2E-06). The known top PD-associated variant (3' variant rs356182) had an opposite direction of effect in iRBD compared to PD.Interpretation: There is a distinct pattern of association at the SNCA locus in RBD as compared to PD, with an opposite direction of effect at the 3' of SNCA. Several 5' SNCA variants are associated with iRBD and with pRBD in overt synucleinopathies. ANN NEUROL 2020;87:584-598. [ABSTRACT FROM AUTHOR]

Presents a study that investigated friction and wear of plasma-deposited diamond films. Experimental procedures for the preparation of the diamond films; Conditions of friction and wear experiment; Characterization of diamond films.

Presents a study that developed a diamond film using microwave plasma assisted chemical vapor deposition. Use of several analytical techniques including Rutherford backscattering and Raman spectroscopy; Properties of diamonds; Discussion on diamond film deposition.

Presents a theoretical and experimental characterization of positive-column plasmas in oxygen glow discharge. Features of positive columns in oxygen glow discharges; Overview of the model used for the oxygen discharge positive column; Experimental measurements on the oxygen discharge.

This article investigates empirically the ethical values of law students in Hong Kong in their final two years of legal education. It first analyses the demographics of these law students before examining their responses to different ethical dilemmas. The findings suggest that feminisation has taken place in Hong Kong law schools. The study also found that a new generation of law students is emerging in Hong Kong that put more emphasis on the value of work-life balance. Finally, the article argues that common law education has enhanced the professionalism of law students in Hong Kong and has contributed to their development of such professional values as ‘professional integrity’, ‘obedience to the law’ and ‘civil duty’. [ABSTRACT FROM PUBLISHER]

The human intestine harbours a complex community of microorganisms, known as the gut microbiota. Significant progress in microbiota research has not only provided knowledge into its composition and abundance, but has also elucidated its crucial functions and potential applications to human health and disease. This review will summarize the key understandings of the gut microbiota to date, with particular emphasis on gut microbiota development and the mechanisms for microbial interactions with the host immune system and the intestinal epithelium. Finally, it will explore the potential microbiota therapies currently being researched, and discuss some of the challenges of translating the current evidence from basic science to human trials. [ABSTRACT FROM AUTHOR]

The article offers information on the implementation of the 'Provisional Stipulations on Open Access to Information in People's Procuratorate Cases' by the Supreme People's Procuratorate of China on October 1, 2014. It informs that the Stipulations aimed at increasing the open public access to information about legal cases and strengthening the transparency of procurators' works in the country. It also mentions that Stipulations may result in effective dissemination of information in cases.

The article provides an answer to a question of how to diagnose the electrocardiography (ECG) reading of a patient with paroxysmal supraventricular tachycardia with no discernible P waves.

Basal cell carcinoma (BCC) is highly curable by surgical excision or radiation. In rare cases, BCC can be locally destructive or difficult to surgically remove. Hedgehog inhibition (HHI) with vismodegib or sonidegib induces a 50–60% response rate. Long-term toxicity includes muscle spasms and weight loss leading to dose decreases. This retrospective chart review also investigates the impact of CoQ10 and calcium supplementation in patients treated with HHI drugs at a single academic medical center from 2012 to 2022. We reviewed the charts of adult patients diagnosed with locally advanced or metastatic BCC treated with vismodegib or sonidegib primarily for progression-free survival (PFS). Secondary objectives included overall survival, BCC-specific survival, time to and reasons for discontinuation, overall response rate, safety and tolerability, use of CoQ10 and calcium supplements, and insurance coverage. Of 55 patients assessable for outcome, 34 (61.8%) had an overall clinical benefit, with 25 (45.4%) having a complete response and 9 (16.3%) a partial response. Stable disease was seen in 14 (25.4%) and 7 (12.7%) progressed. Of the 34 patients who responded to treatment, 9 recurred. Patients who were rechallenged with HHI could respond again. The median overall BCC-specific survival rate at 5 years is 89%. Dose reductions or discontinuations for vismodegib and sonidegib occurred in 59% versus 24% of cases, or 30% versus 9% of cases, respectively. With CoQ10 and calcium supplementation, only 17% required a dose reduction versus 42% without. HHI is highly effective for treating advanced BCC but may require dosing decreases. Sonidegib was better tolerated than vismodegib. CoQ10 and calcium supplementation can effectively prevent muscle spasms. [ABSTRACT FROM AUTHOR]

This photograph depicts a gateway at the Oud Sint-Janshospitaal, a medieval Flemish hospital. This hospital was open to the poor and sick, helping to make health care accessible to the surrounding community. Just as it was in the Middle Ages, health care access is a salient issue today. [ABSTRACT FROM AUTHOR]

Adoptive T-cell therapy (ACT) using tumor-infiltrating lymphocytes (TIL) can induce tumor regression in up to 50% or more of patients with unresectable metastatic melanoma. However, current methods to expand melanoma TIL, especially the “rapid expansion protocol” (REP) were not designed to enhance the generation of optimal effector-memory CD8+ T cells for infusion. One approach to this problem is to manipulate specific co-stimulatory signaling pathways to enhance CD8+ effector-memory T-cell expansion. In this study, we determined the effects of activating the TNF-R family member 4-1BB/CD137, specifically induced in activated CD8+ T cells, on the yield, phenotype, and functional activity of expanded CD8+ T cells during the REP. We found that CD8+ TIL up-regulate 4-1BB expression early during the REP after initial TCR stimulation, but neither the PBMC feeder cells in the REP or the activated TIL expressed 4-1BB ligand. However, addition of an exogenous agonistic anti-4-1BB IgG4 (BMS 663513) to the REP significantly enhanced the frequency and total yield of CD8+ T cells as well as their maintenance of CD28 and increased their anti-tumor CTL activity. Gene expression analysis found an increase in bcl-2 and survivin expression induced by 4-1BB that was associated with an enhanced survival capability of CD8+ post-REP TIL when re-cultured in the absence or presence of cytokines. Our findings suggest that adding an agonistic anti-4-1BB antibody during the time of TIL REP initiation produces a CD8+ T cell population capable of improved effector function and survival. This may greatly improve TIL persistence and anti-tumor activity in vivo after adoptive transfer into patients. [ABSTRACT FROM AUTHOR]

Abstract: Three network convergence, namely, the integration of telecommunications, broadcasting and Internet networks, is a state policy of China for promoting network convergence. Past studies undertaken on the development of Chinese information and communications technology industry adopt different approaches like bargaining, and input–output perspectives. This paper, instead, analyses the implementation of the convergence project from a new institutional perspective. It argues that that the two ministries for the telecommunications and broadcasting sectors, namely, the Ministry of Industry and Information Technology (MIIT) and State Administration of Radio, Films and Television (SARFT) had inertia to attain mutual penetration of networks. It also argues that the ideological disparities of MIIT and SARFT cause them to respond differently to the convergence project. In order to attain the policy goal, the Central Government had to impose a reform schedule from the top and take initiatives at local level to accelerate the policy implementation. It also argues that SARFT and MIIT had developed different patterns of collaboration at local level due to institutional and competitive pressures as well as political pressure from the Central Government. [Copyright &y& Elsevier]

The article analyzes the varying loan regulations followed by China during the conversion of its state-owned banks into actual commercial banks. It looks into the implementation problems related to such loan regulations and the legal reform strategy adopted for such regulatory alterations. It also evaluates the concept of legal gradualism which has come forth from such reforms.

Abstract: Unlike most developed jurisdictions around the world, Hong Kong has not yet adopted a general competition law. However, starting in the 1990s, the city developed a ‘sector-specific’ competition law regime for the telecommunications sector, but in recent years, the effectiveness of such a regime has been challenged. In response, in March 2006, the government issued a consultation paper proposing the adoption of a unified Communications Authority and a unified Communications Ordinance. Then, in May 2008, another consultation paper was issued advocating the introduction of a general competition law. Thus, Hong Kong is moving away from the existing ‘sector-specific’ competition law in its telecommunication regulation. This article traces the development of the ‘sector-specific’ competition law regime and evaluates its limitations. It then considers the government proposals for the establishment of a unified regulator and a unified law for the entire communications sector. It also assesses whether these proposals of regulatory consolidation can improve competition in the local telecommunications sector. Finally, it argues that the current ‘sector-specific’ regulatory regime has become increasingly ineffective in regulating competition in the Hong Kong telecommunications sector, which can only be remedied by the introduction of a general competition law as advocated by the government in its latest consultation paper. [Copyright &y& Elsevier]

The CACHERPframework leverages the relative object popularity as the sole parameter for dynamic cache size tuning. In the process it consistently maintains the prescribed cache hit ratio on the fly by deriving the popularity ratio from the current statistics. As a result the accuracy of the statistical CACHERPoperation is independent of changes in the Internet traffic pattern that may switch suddenly. The contribution by the novel CACHERPframework is that by adaptively maintaining the given hit ratio it effectively reduces the end-to-end information retrieval roundtrip time (RTT) and frees more bandwidth for sharing. This bandwidth would otherwise be consumed in transferring large amounts of data from remote data sources to the proxy server before it is given to the client or requestor. [ABSTRACT FROM AUTHOR]

Heart failure (HF) is characterized by marked prolongation of action potential duration and reduction in cellular repolarization reserve. These changes are caused in large part by HF-induced K+ current downregulation. Molecular mechanisms underlying these changes remain unclear. We determined whether downregulation of K+ currents in a canine model of tachycardia-induced HF is caused by altered expression of underlying K+ charmel α- and β-subunits encoding these currents. K+ channel subunit expression was quantified in normal and failing dogs at the mRNA and protein levels in epicardial (Epi), midmyocardial (Mid), and endocardial (Endo) layers of left ventricle. Analysis of mRNA and protein levels of candidate genes encoding the transient outward K+ current (1to) revealed marked reductions in canine cKv4.3 expression in HF in Epi (44% mRNA, 39% protein), Mid (52% mRNA, 34% protein), and Endo (49% mRNA, 73% protein) layers and a paradoxical enhancement (41% Epi, 97% Mid, 113% Endo) in cKv1.4 protein levels, without significant changes in Kv channel-interacting protein cKChIP2 expression. Expression of cKir2.1, the gene underlying inward rectifier K+ current (1K1), was unaffected by HF at mRNA and protein levels despite significant reduction in 1K1, whereas canine ether-à-go-go-related gene (cERG), which encodes the rapidly activating component of the delayed rectifier current (IK), exhibited increased protein expression. HF was not accompanied by significant changes in cKvLQT1 or cMinK mRNA and protein levels. These data indicate that 1) downregulation of 1to in HF is associated with decreased cKv4.3 and not cKv1.4 or cKChIP2, and 2) alterations in both the rapidly activating and slowly activating components of 1K as well as 1K1 in nonischemic dilated cardiomyopathy are not caused by changes in either transcript or immunoreactive protein levels of relevant channel subunits, which suggests posttranslational modification of these currents by HF. [ABSTRACT FROM AUTHOR]

Phenotypic differences in transient outward K+ current of human and canine ventricular myocytes: insights into molecular composition of ventricular Ito. Am J Physiol Heart Circ Physiol 286: H602–H609, 2004. First published October 2, 2003; 10.1152/ajpheart.00673.2003.—The Ca²+-independent transient outward K+ current (Ito) plays an important electrophysiological role in normal and diseased hearts. However, its contribution to ventricular repolarization remains controversial because of differences in its phenotypic expression and function across species. The dog, a frequently used model of human cardiac disease, exhibits altered functional expression of Ito. To better understand the relevance of electrical remodeling in dogs to humans, we studied the phenotypic differences in ventricular Ito of both species with electrophysiological, pharmacological, and protein-chemical techniques. Several notable distinctions were elucidated, including slower current decay, more rapid recovery from inactivation, and a depolarizing shift of steady-state inactivation in human vs. canine Ito. Whereas recovery from inactivation of human Ito followed a monoexponential time course, canine Ito recovered with biexponential kinetics. Pharmacological sensitivity to flecainide was markedly greater in human than canine Ito, and exposure to oxidative stress did not alter the inactivation kinetics of Ito in either species. Western blot analysis revealed immunoreactive bands specific for Kv4.3, Kvl.4, and Kv channel-interacting protein (KChIP)2 in dog and human, but with notable differences in band sizes across species. We report for the first time major variations in phenotypic properties of human and canine ventricular Ito despite the presence of the same subunit proteins in both species. These data suggest that differences in electrophysiological and pharmacological properties of Ito between humans and dogs are not caused by differential expression of the K channel subunit genes thought to encode Ito, but rather may arise from differences in molecular structure and/or posttranslational modification of these subunits. [ABSTRACT FROM AUTHOR]

Keloids are an excessive accumulation of extracellular matrix. Although numerous studies have shown elevated plasminogen activator inhibitor-1 (PAI-1) levels in keloid fibroblasts compared with those of normal skin. Their specific mechanisms involved in the differential expression of PAI-1 in these cell types. In this study, the upregulation of PAI-1 expression is demonstrated in keloid tissues and their derived dermal fibroblasts, attesting to the persistence, if any, of fundamental differences between in vivo and in vitro paradigms. We further examined the mechanisms involved in hypoxia-induced regulation of PAI-1 gene in dermal fibroblast derived from keloid lesions and associated clinically normal peripheral skins from the same patient. Primary cultures were exposed to an environmental hypoxia or desferroxamine. We found that the hypoxia-induced elevation of PAI-1 gene appears to be regulated at both transcriptional and post-transcriptional levels in keloid fibroblasts. Furthermore, our results showed a consistent elevation of HIF-1α protein level in keloid tissues compared with their normal peripheral skin controls, implying a potential role as a biomarker for local skin hypoxia. Treatment with antisense oligonucleotides against hypoxia-inducible factor 1α (HIF-1α) led to the downregulation of steady-state levels of PAI-1 mRNA under both normoxic and hypoxic conditions. Conceivably, our results suggest that HIF-1α may be a novel therapeutic target to modulate the scar fibrosis process. [ABSTRACT FROM AUTHOR]

On 24 April, 2001, Hong Kong adopted a new Domain Name Dispute Resolution Policy. This represents the efforts of Hong Kong to strengthen management of its domain name disputes, particularly for 'cybersquatting' cases. This article first analyses the salient features of the Policy, including grounds for complaints, rights of complainants, confusingly similar domain names, use of domain names, evidence of registration and use in bad faith, and legitimate interests of domain name owners. The article evaluates the merits of the Policy, including its flexibility, low cost and time-saving efficiency. It also evaluates its demerits, including its restrictive scope, bias toward trademark owners, inadequate coverage for 'reverse domain name hijacking', limited range of remedies, and possibilities for further court proceedings. The article then concludes that the Policy is laudable as it demonstrates the determination and intention of Hong Kong to observe the international standards and practice in its information technology laws. [ABSTRACT FROM AUTHOR]

Examines the mechanism of alpha-adrenergic regulation of expressed hKv4.3 currents. Difference in the channel genes underlying the transient outward potassium current; Complication on the effect of alpha-adrenergic modulation by the isoforms of Kv4; Effect on the mutation of protein kinase C site in hKv4.3.

Presents information on a study which investigated the mechanism involved in the regulation of potassium currents by adrenergic stimulation. Background on transient outward potassium currents; Methodology; Results of the study.

The article offers information on the opinion piece "Opinion on Further Strengthening the Discipline of Law Firms" issued by the All China Lawyers' Association (ACLA) on March 29, 2013. It informs that the opinion focuses on strengthening the state of lawyers' discipline in China. It mentions that the opinion proposes disciplinary reforms in complaint investigation process, complaints-handling processes, and public notification system.

Purpose: To evaluate the anterior scleral shape regional differences between Asian and Caucasian populations. Methods: The study included 250 Asian eyes and 235 Caucasian eyes from participants aged 22 to 67 years (38.5 ± 7.6). Three-dimensional (3D) corneo-scleral maps were acquired using a corneo-scleral topographer (Eye Surface Profiler, Eaglet Eye BV) and used to calculate sagittal height. For each 3D map, the sclera (maximum diameter of 18 mm) and cornea were separated at the limbus using an automated technique. Advanced data processing steps were applied to ensure levelled artefact-free datasets to build an average scleral shape map for each population. Results: Statistically, Asian and Caucasian sclerae are significantly different from each other in sagittal height (overall sclera, p = 0.001). The largest difference in sagittal height between groups was found in the inferior-temporal region (271 ± 203 µm, p = 0.03), whereas the smallest difference was found in the superior-temporal region (84 ± 105 µm, p = 0.17). The difference in sagittal height between Caucasian and Asian sclera increases with the distance from the limbus. Conclusions: Asian anterior sclera was found to be less elevated than Caucasian anterior sclera. However, the nasal area of the sclera is less elevated than the temporal area, independently of race. Gaining knowledge in race-related scleral topography differences could assist contact lens manufacturers in the process of lens design and practitioners during the process of contact lens fitting. [ABSTRACT FROM AUTHOR]

In this article the authors reflect on the use of catheter ablation to reduce the rate of progression of paroxysmal to persistent atrial fibrillation. In the article the authors offer their opinions on the use of catheter ablation and on several points which are raised in the article "Effect of Catheter Ablation on Progression of Paroxysmal Atrial Fibrillation" by K. Jongnarangsin et al.

The article reports on the changes in the principles and regulation in China that aims to strengthen the judicial ethics in nation. It notes that the Supreme People's Court of China promulgated a revised version of the Basic Principles of the Professional Ethics of Judges, together with a similar revised version of the Regulation on Judicial Behaviour, on December 6, 2010. It provides examples related to the changes in the principles, which outlines the general obligations that judges are to observe in discharging their duties. It also offers situations regarding the changes in the regulations, which presents detailed procedures for judges to follow in their daily administration of justice.

The article focuses on the annual working report of Mr. Wang Shengjun, the President of the Supreme People's Court of China, and the measures developed by the Department of Justice to sanction the unlawful activities of lawyers. Wang highlights the problems being faced in the Chinese courts including ineffective guidance and supervision and the poor attitudes of judges. It mentions that the report showed an increasing number of court cases in the Supreme Court with 13,318 ongoing cases in 2009 and 11,749 concluded cases. The article explains that the measures prohibit lawyers from practicing in more than one law firm.

The article discusses the issue of legal ethics in China relative to the bribing of judges by lawyers. It cites three bribery cases which include the case of former President of City Western District People's Court Guo Shenggui who received a sentence of death penalty, the case of six lawyers in Anhui Province who bribed two judges of the Intermediate Level People's Court of Fuyang City and the President of Taihe County People's Court and the case of a client called Li Huaxin whose court litigation was dealt by the High Level People's Court of Guangdong Province. It notes the criminal sanctions inflicted to lawyers involved these cases including Zhang Ruping, Wu Min, Gao Guilan, and Jiang Lihua.

The article provides information on The Five Prohibitions notice promulgated by the Supreme People's Court in line with improving judicial ethics in China. It states that the Notice prevents judges in the country from engaging in five categories of conduct, which are receiving or accepting of gifts from parties in court litigation, having improper contact with lawyers, intervening in court cases of other judges, engaging in corruption for personal gain, and disclosing secrets in judicial work. Furthermore, the Notice sets out sanctions for breaches.

This study examined the effects of overnight orthokeratology (OK) on higher-order wavefront aberrations (HOA), axial length elongation, and accommodation. Low to moderate myopic subjects with healthy eyes wore OK lenses nightly for 9 months. Corneal topography wavefront aberrations and accommodation were measured approximately monthly. Linear mixed-effects models were used to examine the association between the change in peripheral corneal parameters relative to the central cornea with HOA, and the association of accommodation and axial length elongation with HOA. Thirty-three participants (mean age 19.61 years) were included. Mean baseline refraction was −2.97 D (range, −1.0 to −5.0 D). The level of spherical aberration (SA) was associated with a change in relative superior-central corneal thickness (β = −0.21, SE = 0.10, p < 0.037) and with the increased difference in superior-central corneal curvature (β = 0.34, SE = 0.15, p = 0.026). The change of coma increased with the change in relative superior corneal curvature (β = 0.84, SE = 0.18, p < 0.001). Axial length elongation was associated with both horizontal coma (β = 0.19, SE = 0.07, p = 0.018) and SA (β = 0.20, SE = 0.07, p = 0.003). While accommodation and axial length were correlated with HOA, axial length elongation was not correlated with accommodation in OK lens wearers. [ABSTRACT FROM AUTHOR]

Examines the properties of polycrystalline diamond films cultured by chemical vapor deposition. Appearance of the film after bombardment; Presence of Raman peaks; Use of the pin-on-disk technique to study wear and tear properties.

Examines the nucleation and growth of diamond on pretreated silicon substrates. Use of microwave plasma enhanced chemical vapor deposition technique; Density average of diamond nucleation; Result of diamond deposition without pretreatment.

Acral lentiginous melanoma (ALM) is a type of melanoma that is traditionally seen on the soles of the feet, palms of the hand, and under the fingernails or toenails. It is the least frequently diagnosed melanoma among the four histologic subtypes of cutaneous melanoma, accounting for less than 5% of all cases. ALM is frequently diagnosed at late stages and has higher incidences in non-white populations in relation to the other forms of cutaneous malignant melanoma. The most common sites of metastases in melanoma are the skin and subcutaneous tissue followed by lung, liver, brain, and bone. Bone metastases from malignant melanoma usually occur in patients who already have widespread metastases. We present this paper as a unique case study of ALM lesion in an 84-year-old African American male presenting originally in the base of right fifth toe plantar aspect then found multiple bone metastases without any other organ involved. [ABSTRACT FROM AUTHOR]

Immune checkpoint therapy has revolutionized cancer treatment by blocking inhibitory pathways in T cells that limits the an effective anti-tumor immune response. Therapeutics targeting CTLA-4 and PD1/PDL1 have progressed to first line therapy in multiple tumor types with some patients exhibiting tumor regression or remission. However, the majority of patients do not benefit from checkpoint therapy emphasizing the need for alternative therapeutic options. Lymphocyte Activation Gene 3 (LAG3) or CD223 is expressed on multiple cell types including CD4+ and CD8+ T cells, and T regs , and is required for optimal T cell regulation and homeostasis. Persistent antigen-stimulation in cancer or chronic infection leads to chronic LAG3 expression, promoting T cell exhaustion. Targeting LAG3 along with PD1 facilitates T cell reinvigoration. A substantial amount of pre-clinical data and mechanistic analysis has led to LAG3 being the third checkpoint to be targeted in the clinic with nearly a dozen therapeutics under investigation. In this review, we will discuss the structure, function and role of LAG3 in murine and human models of disease, including autoimmune and inflammatory diseases, chronic viral and parasitic infections, and cancer, emphasizing new advances in the development of LAG3-targeting immunotherapies for cancer that are currently in clinical trials. [ABSTRACT FROM AUTHOR]

Necrotizing enterocolitis (NEC) is characterized by intestinal injury and impaired mucin synthesis. We recently showed that breast milk exosomes from rodents promote intestinal cell viability, epithelial proliferation, and stem cell activity, but whether they also affect mucus production is unknown. Therefore, the aim of this study was to investigate the effects of bovine milk-derived exosomes on goblet cell expression in experimental NEC and delineate potential underlying mechanisms of action. Exosomes were isolated from bovine milk by ultracentrifugation and confirmed by Nanoparticle Tracking Analysis and through the detection of exosome membrane markers. To study the effect on mucin production, human colonic LS174T cells were cultured and exposed to exosomes. Compared to control, exosomes promoted goblet cell expression, as demonstrated by increased mucin production and relative expression levels of goblet cell expression markers trefoil factor 3 (TFF3) and mucin 2 (MUC2). In addition, exosome treatment enhanced the expression of glucose-regulated protein 94 (GRP94), the most abundant intraluminal endoplasmic reticulum (ER) chaperone protein that aids in protein synthesis. Furthermore, experimental NEC was induced in mouse pups by hyperosmolar formula feeding, lipopolysaccharide administration and hypoxia exposure on postnatal days 5–9. Milk exosomes were given with each gavage feed. NEC was associated with ileal morphological injury and reduction in MUC2+ goblet cells and GRP94+ cells per villus. Exosome administration to NEC pups prevented these changes. This research highlights the potential novel application of milk-derived exosomes in preventing the development of NEC in high-risk infants when breast milk is not available. [ABSTRACT FROM AUTHOR]