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This article argues that environmental considerations fall within the scope of medical bioethics, and there are implications specific to medical education. It endorses the need to expand the scope and epistemology of contemporary medical bioethics discourse by including themes related to environmental considerations. Our discussion begins by providing a brief history of environmental bioethics. It then offers a critique of three specific health and environmental issues, namely technology, toxics, and consumption, and discusses how these issues are key to articulating moral considerations of human health and subsequently medicine and its teaching. Lastly, it explores criticisms of including environmental issues into the bioethical debate before providing suggestions of how environmental ethics can be included into the medical curriculum. This article concludes by suggesting theoretical possibilities for environmentally inclusive bioethics, such as reorienting bioethical discussions to its original environmental advocacy and supporting environmental bioethics as a competency in medical education. [ABSTRACT FROM AUTHOR]

Surgery for ossification of the ligamentum flavum (OLF) comes with a relatively high risk of dural tear. We report a 50-year-old woman, who presented with symptomatic spinal stenosis from OLF at T11–T12 and lower lumbar spondylosis for which a single stage posterior decompression and instrumented fusion of both sites was done. Removal of the OLF resulted in a small dural tear with intact arachanoid which was covered using a fibrin sealant. In the first post-operative day, the patient's neurology started deteriorating. An MR scan was done to look for hematoma. It showed the spinal cord herniating out of the thecal sac at the operated level. Emergency re-operation was done to reduce the herniation and the dural defect was repaired. The patient gradually recovered to her best functional status. Based on this experience, we advise primary repair of inadvertent durotomies. [ABSTRACT FROM AUTHOR]

The article discusses the importance and decline of post-mortem examinations, or autopsies, in understanding the cause of death. The author reflects on a case where the cause of death was listed as "sepsis of unknown origin" and expresses a desire for a post-mortem examination to provide definitive answers. However, the family did not want a post-mortem and prioritized their own grieving process. The article highlights the shift towards a patient-centered and family-centered approach to death, recognizing the relational and spiritual aspects of the process. It emphasizes the importance of open communication and respect for the individual and their loved ones. [Extracted from the article]

Use of the serious illness conversation guide to improve communication with surrogates of critically ill patients. The term "stable" acknowledges neither the long and arduous journey of critically ill COVID-19 patients, nor the various levels of support they require to maintain survival. 10.1097/CCM.0000000000002169 15 ICS (2020) ICS Guidance on the use of video communication for patients and relatives in ICU [Online]. Before COVID-19, I thought little about using the word "stable" in critically ill patient updates. [Extracted from the article]

Anti-malware software must be frequently updated in order to protect the system and the user from attack. Makers of this software must choose between interrupting the user to update immediately or allowing them to update later. In either case, assessing the content of the interruption may still require cognitive investment. However, by allowing the user to negotiate a delayed response to these interruptions, users can instead focus on their work. This paper experimentally examines the effect of immediate and negotiated interruptions on user decision time and decision accuracy in multiple stage tasks. For complex tasks, decision performance is higher when the user can negotiate the onset of and response to interruptions. The option to defer response also results in greater subjective perceptions of control, improved task resumption and reduced feelings of interruption and distraction on the part of the user, even within a short period of time. These findings have practical implications for endpoint security and where there is a need to mitigate the effects of user interruptions from computer-mediated communication in complex task situations. [ABSTRACT FROM AUTHOR]

The treatment of atypical femoral shaft fractures with abnormal bowing provides a unique challenge for surgeons. Whilst intramedullary fixation of atypical femoral shaft fractures affords both mechanical and biological benefits, the mismatch between standard intramedullary devices and the abnormal femoral bowing in these patients makes this method of fixation challenging for the surgeon. The purpose of this manuscript is to illustrate the evolution of our surgical technique through a series of four patients. The critical factors we identified include lateral positioning of the patient for reduction, the use of a piriformis-start nail, and an entry point that was anterior in the sagittal profile and lateral in the coronal profile. This technique was easily replicable, facilitated more anatomical reduction and aided in avoiding complications. [ABSTRACT FROM AUTHOR]

Through music, they were transported beyond the confines of the intensive care unit (ICU). I Oblique et coupant l'ombre un torrent éclatant i I Ruisselait en flots d'or sur la dalle polie i I Où les atomes d'ambre au feu se miroitant i I Mêlaient leur sarabande à la gymnopédie i I Slanting and shadow-cutting a bursting stream i I Trickled in gusts of gold on the shiny flagstone i I Where the amber atoms in the fire gleaming i I Mingled their sarabande with the gymnopaedia. i I - J.P. Contamine de Latour i Leigh started playing her guitar outside the double doors leading into the first bay of four female patients. The ICU bay became, with Leigh's presence and music, a seaside lounge. [Extracted from the article]

Abstract: Aim: Superficial soft tissue sarcomas (S‐STS) are generally considered low‐risk tumors and have an excellent prognosis when treated with appropriate surgery and adjuvant therapy. However, they are often misdiagnosed then mistreated, leading to significant morbidity. This study aims to examine the patterns of care and outcomes of patients with S‐STS, comparing those initially managed through sarcoma units versus elsewhere. Methods: Patients with S‐STS from Prince of Wales Hospital in NSW (1995–2013) and Peter MacCallum Cancer Centre in Victoria (2009–2013) were identified from a national sarcoma database. Baseline variables, treatment and disease outcomes were recorded. Statistical tests performed included univariate and multivariate analyses, chi‐square tests, as well as the Kaplan–Meier method for 5‐year local recurrence and survival rates. Results: Eighty‐nine patients were identified, with 35% initially managed at a sarcoma unit and 65% elsewhere. Patients initially managed at sarcoma units had larger tumors (>5 cm 39% vs 17%; P  =  0.036) with a trend to higher grade (61% vs 48%; P = 0.39). Patients that were initially managed outside a sarcoma unit more often underwent open surgical biopsies (P < 0.0005), had multiple operations (P < 0.0005) and had higher rates of local recurrences (24% vs 6.5%, P  =  0.038). They also had lower 5‐year local recurrence‐free survival rates (P = 0.022), but had higher metastasis‐free survival (P = 0.014). On multivariate analysis, only larger STS size and male gender predicted for poorer metastasis‐free survival (P = 0.042 and 0.018, respectively). Conclusion: Patients with S‐STS initially managed outside specialized sarcoma units undergo more operations, with risk of greater morbidity, and have greater risk of local recurrence. [ABSTRACT FROM AUTHOR]

Background: Clinical outcomes of terrible triad injuries (TTIs) of the elbow are historically poor. To date, it is still debatable whether the coronoid needs to be fixed and if so, how and in which sequence.Methodology: Between 2010 and 2013, 13 patients were treated surgically for acute TTIs of the elbow at a Tertiary Level 1 Trauma Centre by a single surgeon, using a standardized protocol, which included coronoid-brachialis complex fixation via pull-through trans-osseous sutures, radial head fixation or prosthetic replacement and a repair of the lateral ulnar collateral ligament. Repair of the medial collateral ligament (MCL) was done if valgus-stress test demonstrated persistent instability. Patients were then followed-up with clinical and radiological evaluation by the senior author until fracture union and elbow range of motion reached a plateau. Outcomes measured were range of motion, DASH scores and MEPS, as well as surgical complications.Results: Intraoperative stability was achieved in all 13 cases, MCL repair was required in 3 cases and application of external fixation was not required in any case. Patients were followed-up for an average length of 27.7 months and the minimum follow-up period was 12 months. The average age of patients was 46.4 years (range 35-79 years old) at the time of trauma. This included eight Regan-Morrey Type I and five Regan-Morrey Type II coronoid fractures, with ten Mason Type I/II and three Mason Type III radial head fractures. The average arc of ulno-humeral motion was 105.0° (range 80°-135°). The average flexion contracture was 15.0° (range 0°-40°). The average supination-pronation arc was 114.9° (range 0°-180°). The average MEPS was 85 of 100 (range 45-100) and the average DASH score was 21.2 of 100 (range 1.7-61.2). A single case of radio-ulnar synostosis, heterotropic ossification and two cases of recurrent elbow instability were noted.Conclusions: The coronoid-first surgical approach, using a suture-lasso fixation method, has technical benefits for us and showed good clinical success in our series. This is important with postero-medial rotatory instability being common in our series of TTIs. We emphasize not to miss a TTI in an apparently isolated low Mason class radial head fracture. [ABSTRACT FROM AUTHOR]

Purpose: Recently, we have shown that combining mouth rinsing with the ingestion of a 2 mM quinine solution immediately before a 30-s cycling sprint significantly improves performance. However, the strong bitterness of such a solution produces an unpleasant taste and evokes nausea at higher concentrations. Given the possibility that mouth rinsing with quinine without ingesting it may not produce nausea, a mouth rinse only protocol may be a more practical approach to administer quinine for improving exercise performance. The purpose of the present study was to determine whether mouth rinsing with quinine without ingesting it improves 30-s sprint cycling performance. Methods: Twelve competitive male cyclists performed a 30-s maximal cycling sprint immediately after rinsing their mouth for 10 s with either a 10 mM bitter quinine solution (QUI), plain water (WAT), a 7.1 % w/v sweet glucose solution (GLU), or no solution at all (control; CON). Sprint performance was assessed, and heart rate, ratings of perceived exertion and blood variables were measured pre- and post-exercise. Results: Mean power output during the 30-s sprint (QUI 888 ± 38; CON 873 ± 39; WAT 885 ± 37; GLU 873 ± 42 W; p = 0.431) as well as peak power (QUI 1230 ± 61; CON 1,208 ± 65; WAT 1,220 ± 70; GLU 1,202 ± 59 W; p = 0.690) were similar between the four conditions. There were no significant differences in any other performance measures, heart rate, subjective ratings or blood variables between conditions. Conclusions: Mouth rinsing with a bitter tasting quinine solution without ingestion does not improve 30-s sprint cycling performance. [ABSTRACT FROM AUTHOR]

Foreign bodies in the heart are rare occurrences with a limited evidence base to guide recommendations on management. We report a case of multiple cardioembolic strokes as a result of a self-inflicted sewing needle puncture from the anterior chest through the right ventricle and interventricular septum with its tip in the left ventricle close to the subvalvular apparatus in a 39-year-old psychiatric patient. We discuss issues surrounding decision making and ongoing care and highlight the importance of further follow-up and reporting of cases to form a robust evidence base to guide future recommendations. [ABSTRACT FROM AUTHOR]

The rise of social networking platforms provides opportunities to examine the relationship between public emotion and housing price. This study investigates frequency and places of visits, population sentiment, and housing price using 8.7 million tweets retrieved from Manhattan, New York City in 2019. We implemented kernel density estimation, Getis-Ord G i hot spot analysis, and spatial lagged hedonic pricing models to identify the location variation of sentiment levels. The results show: (1) the spatial clustering of tweets frequency was highly related to land use types in places such as parks, financial districts, and train stations; (2) high sentiment levels coincided with high frequency clusters and higher positive sentiment is associated with higher housing price; and (3) sentiment level was significantly associated with housing price and building structure, amenities, and proximity to landmarks all had significant influences on housing price. The study indicates that a population with higher concentration of happiness correlates to higher property value and provides an innovative perspective to understand public sentiment in relation to housing price using social media data, supplemented by housing transaction data. We demonstrate a feasible framework for researchers and stakeholders to utilize in future urban and spatial geographical research. • Identify spatial clustering of tweets frequency and land use types. • Assess spatiotemporal characteristic of public sentiment using Twitter data. • Evaluate the relationship of public sentiment level to housing price at a neighborhood scale. [ABSTRACT FROM AUTHOR]

Introduction: The Singapore Armed Forces (SAF) recognises the potential benefits and looks to harnessing telemedicine for primary health care services. In this prospective self-controlled pilot study, we aimed to evaluate the safety, efficiency and user satisfaction outcomes of virtual care (VC) at a military medical centre.Methods: Out of 320 patients seen during the study period, 28 were enrolled in this study and underwent on-premises VC, comprising digital symptoms collection and telemedicine in addition to the usual in-person physician consultation. Safety outcomes were measured based on the diagnostic concordance between physicians. Efficiency was measured based on consultation times, and user satisfaction was evaluated using a standard questionnaire.Results: There was a higher caseload of both upper respiratory infections and dermatological conditions in our population, in which telemedicine performed well. In terms of safety, telemedicine achieved a mean diagnostic concordance of 92.8% compared to in-person consultations. In terms of efficiency, consultation times were 26.2% - or 2 minutes and 15 seconds - shorter on average with telemedicine (p = 0.0488). User satisfaction was favourable, with 85.5% of patients satisfied with the VC experience.Discussion: This study has been invaluable in showing that on-premises telemedicine is a safe, efficient and effective means to extend and increase our surge capacity for primary health care. Our results have given us reasonable confidence to explore a larger-scale implementation in our network of military medical centres in the future. [ABSTRACT FROM AUTHOR]

Study Design: Retrospective comparative radiological study. Purpose: To analyze the difference in early disc height loss following transforaminal and lateral lumbar interbody fusion (TLIF and LLIF). Overview of Literature: Minimal disc height loss facilitated by the polyaxial screw heads can occur naturally due to mechanical loading following lumbar fusion procedures. This loss does not usually cause any significant foraminal narrowing. However, when there is concomitant cage subsidence, symptomatic foraminal compromise could occur, especially when posterior decompression is not performed. It is not known whether the type of procedure, TLIF or LLIF, could influence this phenomenon. Methods: Retrospectively, patients who underwent TLIF and LLIF for various degenerative conditions were shortlisted. Each of their fused levels with the cage in situ was analyzed independently, and the preoperative, postoperative, and follow-up disc height measurements were compared between the groups. In addition, the total disc height loss since surgery was calculated at final follow-up and was compared between the groups. Results: Forty-six patients (age, 64.1±8.9 years) with 70 cage levels, 35 in each group, were selected. Age, sex, construct length, preoperative disc height, cage height, and immediate postoperative disc height were similar between the groups. By 3 months, disc height of the TLIF group was significantly less and continued to decrease over time, unlike in the LLIF group. By 1 year, the TLIF group demonstrated greater disc height loss (2.30±1.3 mm) than the LLIF group (0.89±1.1 mm). However, none of the patients in either group had any symptomatic complications throughout follow-up. Conclusions: Although our study highlights the biomechanical advantage of LLIF over TLIF in maintaining disc height, none of the patients in our cohort had symptomatic complications or implant-related failures. Hence, TLIF, as it incorporates posterior decompression, remains a safe and reliable technique despite the potential for greater disc height loss. [ABSTRACT FROM AUTHOR]

Purpose: To determine the accuracy of thoracolumbar pedicle screw insertion with the routine use of three-dimensional (3D) intraoperative imaging and navigation over a large series of screws in an Asian population. Overview of Literature: The use of 3D intraoperative imaging and navigation in spinal surgery is aimed at improving the accuracy of pedicle screw insertion. This study analyzed 2,240 pedicle screws inserted with the routine use of intraoperative navigation. It is one of very few studies done on an Asian population with a large series of screws. Methods: Patients who had undergone thoracolumbar pedicle screws insertion using intraoperative imaging and navigation between 2009 and 2017 were retrospectively analyzed. Computed tomography (CT) images acquired after the insertion of pedicle screws were analyzed for breach of the pedicle wall. The pedicle screw breaches were graded according to the Gertzbein classification. The breach rate and revision rate were subsequently calculated. Results: A total of 2,240 thoracolumbar pedicle screws inserted under the guidance of intraoperative navigation were analyzed, and the accuracy of the insertion was 97.41%. The overall breach rate was 2.59%, the major breach rate was 0.94%, and the intraoperative screw revision rate was 0.7%. There was no incidence of return to the operating theater for revision of screws. Conclusions: The routine use of 3D navigation and intraoperative CT imaging resulted in consistently accurate pedicle screw placement. This improved the safety of spinal instrumentation and helped in avoiding revision surgery for malpositioned screws. [ABSTRACT FROM AUTHOR]

The article presents a case study of an 89-year old woman with a history of myocardial infarction and a permanent pacemaker for complete heart block who complained of severe left scapular pain and pleuritic right chest pain eight days after an endoscopic botulinum toxin injection which resulted in her death. The patient was unsuitable for surgical intervention after suffering from an extraluminal swelling following esophagogastroduodenoscopy.

Background: In corona virus disease 2019 (COVID-19), which emerged in December 2019 and is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), most case presentations have been related to the respiratory tract. Several recent studies reveal that angiotensin-converting enzyme 2 (ACE2), which was found in the target cells of the virus, is highly expressed in the lungs, small bowel, and vasculature. Case Report: A 29-year-old male construction worker from India presented with left-sided colicky abdominal pain. He tested positive for infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by reverse transcription-polymerase chain reaction (RT-PCR). Isolated superior mesenteric vein thrombosis was diagnosed by CT (computed tomography) scan. He was managed by anti-coagulants and clinically improved. Conclusions: This case report indicates that isolated venous thrombosis of the abdominal vessels without concurrent arterial thrombosis can be a complication of the hyper-coagulability state in COVID-19 patients. Hence, early evaluation of abdominal vessels in covid-19 patients who present with any abdominal symptoms should be considered, especially when found to have an elevated D-dimer level, as early treatment of thrombosis with low-molecular-weight heparin can have a significant impact on the therapeutic outcome. [ABSTRACT FROM AUTHOR]

Malaysia has reported no indigenous cases of P. falciparum and P. vivax for over 3 years. When transmission reaches such low levels, it is important to understand the individuals and locations where exposure risks are high, as they may be at greater risk in the case of a resurgence of transmission. Serology is a useful tool in low transmission settings, providing insight into exposure over longer durations than PCR or RDT. We ran blood samples from a 2015 population-based survey in northern Sabah, Malaysian Borneo on a multiplex bead assay. Using supervised machine learning methods, we characterised recent and historic exposure to Plasmodium falciparum and P. vivax and found recent exposure to P. falciparum to be very low, with exposure to both species increasing with age. We performed a risk-factor assessment on environmental, behavioural, demographic and household factors, and identified forest activity and longer travel times to healthcare as common risk-factors for exposure to P. falciparum and P. vivax. In addition, we used remote-sensing derived data and geostatistical models to assess environmental and spatial associations with exposure. We created predictive maps of exposure to recent P. falciparum in the study area and showed 3 clear foci of exposure. This study provides useful insight into the environmental, spatial and demographic risk factors for P. falciparum and P. vivax at a period of low transmission in Malaysian Borneo. The findings would be valuable in the case of resurgence of human malarias in the region. [ABSTRACT FROM AUTHOR]

Epidemiological and whole-genome sequencing analysis of an ongoing outbreak of Streptococcus pyogenes (Group A Streptococcus) in London (United Kingdom). Prospective identification of Group A Streptococcus cases from a diagnostic laboratory serving central and south London between 27 November and 10 December 2022. Case notes were reviewed and isolates were retrieved. Case numbers were compared with the previous 5 years. Whole-genome sequencing was performed with long-read, nanopore technology for emm typing and identification of superantigen genes. Associations of pathogen-related factors with an invasive disease were assessed by single-variable and multi-variable logistic regression. Case numbers began increasing in October 2022 from a baseline of 2.0 cases per day, and in December 2022, the average daily case numbers reached 10.8 cases per day, four-fold the number usually seen in winter. A total of 113 cases were identified during the prospective study period. Three quarters (86/113, 76%) were paediatric cases, including 2 deaths. Of 113 cases, 11 (10%) were invasive. In total, 56 isolates were successfully sequenced, including 10 of 11 (91%) invasive isolates. The emm12 (33/56, 59%) and emm1 (9/56, 16%) types were predominant, with 7 of 9 (78%) emm1 isolates being from the M1uk clone. The majority of invasive isolates had superantigen genes spea (7/10, 70%) and spej (8/10, 80%), whereas, in non-invasive isolates, these superantigen genes were found less frequently (spea : 5/46, 11% and spej: 7/46, 15%). By multivariable analysis of pathogen-related factors, spea (OR 8.9, CI 1.4–57, p 0.020) and spej (OR 12, CI 1.8–78, p 0.011) were associated with invasive disease. emm12 and emm1 types predominate in the ongoing outbreak, which mainly affects children. In this outbreak, the spea and spej superantigen genes are associated with the severity of presentation. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which discusses the depiction of thalassemia in paintings made by Renaissance artist Michelangelo including "The Manchester Madonna."

During the first wave of the global COVID-19 pandemic the clinical utility and indications for SARS-CoV-2 serological testing were not clearly defined. The urgency to deploy serological assays required rapid evaluation of their performance characteristics. We undertook an internal validation of a CE marked lateral flow immunoassay (LFIA) (SureScreen Diagnostics) using serum from SARS-CoV-2 RNA positive individuals and pre-pandemic samples. This was followed by the delivery of a same-day named patient SARS-CoV-2 serology service using LFIA on vetted referrals at central London teaching hospital with clinical interpretation of result provided to the direct care team. Assay performance, source and nature of referrals, feasibility and clinical utility of the service, particularly benefit in clinical decision-making, were recorded. Sensitivity and specificity of LFIA were 96.1% and 99.3% respectively. 113 tests were performed on 108 participants during three-week pilot. 44% participants (n = 48) had detectable antibodies. Three main indications were identified for serological testing; new acute presentations potentially triggered by recent COVID-19 e.g. pulmonary embolism (n = 5), potential missed diagnoses in context of a recent COVID-19 compatible illness (n = 40), and making infection control or immunosuppression management decisions in persistently SARS-CoV-2 RNA PCR positive individuals (n = 6). We demonstrate acceptable performance characteristics, feasibility and clinical utility of using a LFIA that detects anti-spike antibodies to deliver SARS-CoV-2 serology service in adults and children. Greatest benefit was seen where there is reasonable pre-test probability and results can be linked with clinical advice or intervention. Experience from this pilot can help inform practicalities and benefits of rapidly implementing new tests such as LFIAs into clinical service as the pandemic evolves. [ABSTRACT FROM AUTHOR]

Objectives: Candida auris has been implicated in ICU outbreaks worldwide and is notable for being difficult to identify and treat, its resilience in the environment, and significant patient mortality associated with invasive disease. Here, we describe a small C. auris outbreak and how it was terminated.Design: Single-center, observational.Setting: Two general adult ICUs at an urban U.K. teaching hospital.Patients: All patients positive for C. auris during the 5-month outbreak were included (n = 7).Interventions: Stepwise implementation of enhanced infection prevention and control precautions was introduced including twice-weekly screening, contact tracing, isolation precautions, and environmental decontamination. A detailed environmental screen was performed to identify potential reservoirs. This included the patient bed space and clinical equipment and a frequently handled cloth lanyard attached to a key used to access controlled drugs. Personal possessions such as mobile phones, lanyards, and identification badges were also screened.Measurements and Main Results: The index case and six linked acquisitions were identified. Four of six (67%) patients were identified after discharge of all known previous C. auris cases from ICU, highlighting potential for an environmental reservoir. Environmental screening identified C. auris from a patient bed space following deep cleaning, prompting review and enhancement of cleaning procedures. The controlled drug cloth lanyard was positive for C. auris, which prompted removal and culture of all staff lanyards. C. auris was identified on 1/100 staff lanyards (1%). No mobile phones or identification badges were positive for C. auris. The outbreak terminated following withdrawal of lanyards from ICU.Conclusions: This outbreak further implicates environmental reservoirs as sustaining C. auris ICU outbreaks. Identification of C. auris on cloth lanyards highlights the need to identify commonly handled moveable objects during an outbreak. We suggest that ICUs with a C. auris outbreak should investigate similar infrequently cleaned items as potential reservoirs and review their policies on lanyard use. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has raised challenges in dealing with information sharing by the public and the authorities. There are two categories of information sharing on social media that are believed to be potentially problematic and unethical: the sharing of personal information of patients and the sharing of fake news or false information. We present a discussion on how the response to the COVID-19 pandemic in Malaysia can be ethically handled in terms of information sharing. It is recommended that the public should cultivate the basic skills to evaluate information and determine its validity. On the other hand, the authorities should refrain from placing the blame on patients to avoid them from being stigmatized. It is crucial that all parties are aware of their ethical duty to ensure only ethical and valid information gets shared on social media. [ABSTRACT FROM AUTHOR]

We investigated the contribution of host immune cells to bacterial killing in a whole-blood bactericidal activity (WBA) assay, an ex vivo model used to test efficacy of drugs against mycobacterium tuberculosis (Mtb). We performed WBA assays with immuno-magnetic depletion of specific cell types, in the presence or absence of rifampicin. Innate immune cells decreased Mtb growth in absence of drug, but appeared to diminish the cidal activity of rifampicin, possibly attributable to intracellular bacterial sequestration. Adaptive immune cells had no effect with or without drug. The WBA assay may have potential for testing adjunctive host-directed therapies acting on phagocytic cells. [ABSTRACT FROM AUTHOR]

This paper presents a semi-analytical approach for electrical performance modeling of complex electronic packages with multiple power/ground planes and large number of vias. The method is based on the modal expansion technique and the method of moments. For the inner package domain with multiple power! ground planes and many vias, the modal expansion method is employed to compute the electromagnetic fields from which the multiport network parameters, e.g., the admittance matrix can be easily obtained. For the top/bottom domain of signal layers, the moment method is used to extract the equivalent resistance, inductance, capacitance, and conductance (RLCG) parameters. The equivalent circuit for the entire package is then generated by combining the results for both package domains. The equivalent circuit can be used in a SPICE-like simulator to study the signal and power integrity of an electronic package. Numerical examples demonstrate that the new approach is able to provide fast yet accurate signal and power integrity analysis of multilayered electronic packages. [ABSTRACT FROM AUTHOR]

Background: Current gene- and cell-based therapies have significant limitations which impede widespread clinical application. Taking diabetes mellitus as a paradigm, we have sought to overcome these limitations by ex vivo electrotransfer of a nonviral insulin expression vector into primary hepatocytes followed by immediate autologous reimplantation in a preclinical model of diabetes. Methods and Results: In a single 3-hour procedure, hepatocytes were isolated from a surgically resected liver wedge, electroporated with an insulin expression plasmid ex vivo and reimplanted intraparenchymally under ultrasonic guidance into the liver in each of 10 streptozotocin-induced diabetic Yorkshire pigs. The vector was comprised of a bifunctional, glucose-responsive promoter linked to human insulin cDNA. Ambient glucose concentrations appropriately altered human insulin mRNA expression and C-peptide secretion within minutes in vitro and in vivo. Treated swine showed correction of hyperglycemia, glucose intolerance, dyslipidemia and other metabolic abnormalities for ≥47 weeks. Metabolic correction correlated significantly with the number of hepatocytes implanted. Importantly, we observed no hypoglycemia even under fasting conditions. Direct intrahepatic implantation of hepatocytes did not alter biochemical indices of liver function or induce abnormal hepatic lobular architecture. About 70% of implanted hepatocytes functionally engrafted, appeared histologically normal, retained vector DNA and expressed human insulin for $47 weeks. Based on structural tissue analyses and transcriptome data, we showed that early correction of diabetes attenuated and even prevented pathological changes in the eye, kidney, liver and aorta. Conclusions: We demonstrate that autologous hepatocytes can be efficiently, simply and safely modified by electroporation of a nonviral vector to express, process and secrete insulin durably. This strategy, which achieved significant and sustained therapeutic efficacy in a large preclinical model without adverse effects, warrants consideration for clinical development especially as it could have broader future applications for the treatment of other acquired and inherited diseases for which systemic reconstitution of a specific protein deficiency is critical. [ABSTRACT FROM AUTHOR]

Ultramafic rocks are considered as the most important geogenic sources of Cr whose hexavalent species is of environmental concern. In tropical to subtropical areas (e.g. New Caledonia, Brazil, Philippines), prolonged and pervasive weathering of ultramafic rocks produces Ni laterite ores which are further enriched in Cr. While elevated levels of Cr have been identified in Ni laterites, Cr availability and export from these deposits and its contribution to natural waters remain poorly understood. Therefore, this study examined the speciation and flux of Cr in a Ni laterite profile through sequential extraction and leaching experiments coupled with physical, mineralogical, and geochemical characterization. These were correlated to the behavior and export of Cr in surrounding surface waters studied through hydrochemical investigation. This work demonstrates, through the example of the Rio Tuba Ni laterite deposit, that pervasive weathering of ultramafic rocks in tropical areas generate very important reservoirs of Cr(VI). Although Cr is primarily fixed in insoluble fractions (>89%) and least in bioavailable and easily mobilizable phases (<1%), due to the inherent elevated Cr content (up to 2.9 wt%) of the Ni laterites, the latter still provided water-extractable Cr(VI) contents surpassing drinking water and freshwater standards. By comparison with the silicate-rich saprolite unit, the overlying Fe-(oxyhydr)oxide dominated laterite layer yielded lower Cr(VI) contents due to its acidic nature and higher amounts of organic matter and Fe-(oxyhydr)oxides which promote reduction and readsorption of Cr(VI). During water infiltration, Cr(VI) migrates downward along the profile at a rate of 62 to 3446 t/km2/yr. While the alkaline and oxidizing conditions of the surrounding surface waters favor Cr(VI) mobilization, only a fraction of Cr(VI) from the Ni laterites reaches these water bodies. Cr(VI) concentrations (≤213 μg/L) and fluxes (mostly ≤50 kg/km2/yr) in the surface waters being significantly lower than that of the Ni laterites reflect the action of processes (e.g. dilution, reduction, adsorption) that attenuate the release of this species along water flow paths. • In the Ni laterites, the bulk of Cr is fixed in recalcitrant minerals while only <1% is bioavailable and easily mobilizable. • Water-extractable Cr(VI) content from the Ni laterite profile surpassed drinking water and freshwater standards. • First attempt to estimate Cr(VI) infiltration flux (62 to 3446 t/km2/yr) in Ni laterites. • Area-normalized Cr(VI) fluxes in surrounding streams are mostly ≤50 kg/km2/yr except during stormflow conditions. [ABSTRACT FROM AUTHOR]

Background: Oral contraceptives are rarely prescribed for women with systemic lupus erythematosus, because of concern about potential negative side effects. In this double-blind, randomized, noninferiority trial, we prospectively evaluated the effect of oral contraceptives on lupus activity in premenopausal women with systemic lupus erythematosus. Methods: A total of 183 women with inactive (76 percent) or stable active (24 percent) systemic lupus erythematosus at 15 U.S. sites were randomly assigned to receive either oral contraceptives (triphasic ethinyl estradiol at a dose of 35 μg plus norethindrone at a dose of 0.5 to 1 mg for 12 cycles of 28 days each; 91 women) or placebo (92 women) and were evaluated at months 1, 2, 3, 6, 9, and 12. Subjects were excluded if they had moderate or high levels of anticardiolipin antibodies, lupus anticoagulant, or a history of thrombosis. Results: The primary end point, a severe lupus flare, occurred in 7 of 91 subjects receiving oral contraceptives (7.7 percent) as compared with 7 of 92 subjects receiving placebo (7.6 percent). The 12-month rates of severe flare were similar: 0.084 for the group receiving oral contraceptives and 0.087 for the placebo group (P=0.95; upper limit of the one-sided 95 percent confidence interval for this difference, 0.069, which is within the prespecified 9 percent margin for noninferiority). Rates of mild or moderate flares were 1.40 flares per person-year for subjects receiving oral contraceptives and 1.44 flares per person-year for subjects receiving placebo (relative risk, 0.98; P=0.86). In the group that was randomized to receive oral contraceptives, there was one deep venous thrombosis and one clotted graft; in the placebo group, there was one deep venous thrombosis, one ocular thrombosis, one superficial thrombophlebitis, and one death (after cessation of the trial). Conclusions: Our study indicates that oral contraceptives do not increase the risk of flare among women with systemic lupus erythematosus whose disease is stable. N Engl J Med 2005;353:2550-8. [ABSTRACT FROM AUTHOR]