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Examines successful women in leadership roles, and discusses the five fundamental elements of the \"centered leadership,\" model--meaning, framing, connecting, engaging, and energizing--with anecdotes about women CEOs and other females working in leadership positions.

Diabetic retinopathy (DR) is a major source of retinal disease and vision loss worldwide. Current treatments fail to address the loss of neurons and are associated with significant side effects. Here, we investigated whether retinal progenitor cells (RPCs) could improve anatomic and functional outcomes in a rat model of DR. Male Long Evans (LE) rats were given streptozotocin (STZ), and the induction of diabetes was confirmed prior to the intravitreal injection of RPCs, either allogeneic (no immunosuppression) or human (with cyclosporin A), at 1 week post-induction. Animals were tested at 6 weeks post-induction via electroretinogram (ERG), optomotor response (OR), and contrast sensitivity (CS). Retinas were harvested post-mortem, 8 weeks post-STZ induction, and analyzed using immunohistochemistry (IHC). In rat RPC-treated eyes, ERG (b-wave, oscillatory potentials), OR, and CS all showed a positive effect for cell treatment versus controls. IHC showed a markedly diminished extravasation of albumin, a decreased VEGF expression, and an improved morphology in cellular and synaptic layers. Human RPC-treated eyes replicated a subset of these results. Together, this provides evidence of both anatomic and functional treatment effects in a rat model of DR, encompassing retinal neuroprotection as well as improved vascular integrity, thereby supporting the further investigation of intravitreal RPCs for the treatment of this condition.

Photoreceptor degeneration is a major cause of untreatable blindness worldwide and has recently been targeted by emerging technologies, including cell- and gene-based therapies. Cell types of neural lineage have shown promise for replacing either photoreceptors or retinal pigment epithelial cells following delivery to the subretinal space, while cells of bone marrow lineage have been tested for retinal trophic effects following delivery to the vitreous cavity. Here we explore an alternate approach in which cells from the immature neural retinal are delivered to the vitreous cavity with the goal of providing trophic support for degenerating photoreceptors. Rat and human retinal progenitor cells were transplanted to the vitreous of rats with a well-studied photoreceptor dystrophy, resulting in substantial anatomical preservation and functional rescue of vision. This work provides scientific proof-of-principle for a novel therapeutic approach to photoreceptor degeneration that is currently being evaluated in clinical trials.

Key Points Implantable cardioverter-defibrillators (ICDs) reduce mortality in patients with increased risk of sudden cardiac death, but use of these devices has been limited by complications with the intravascular leads The subcutaneous ICD (S-ICD) is a new ICD device that avoids placing leads in the cardiac vascular system The S-ICD is safe and effective for the treatment of ventricular tachycarrhythmias, but use of S-ICDs is limited by the lack of pacing or remote monitoring capabilities The S-ICD is most commonly used in young patients at risk for ventricular fibrillation, but not ventricular tachycardia, and without pacing indications Future generations of the S-ICD should allow for expanded use and for subcutaneous leads to be combined with leadless pacing, enabling the S-ICD to become the standard ICD device Implantable cardiac defibrillators (ICD) are effective in reducing mortality in patient populations at risk for sudden cardiac death, but transvenous ICDs are associated with complications such as infections, pneumothorax, venous thrombosis, lead dislodgement, lead malfunction, and haemopericardium. In this Review, Lewis and Gold describe a novel design of entirely subcutaneous ICDs that avoid some of the complications of transvenous systems, and explore the advantages and disadvantages of both ICD systems. The subcutaneous implantable cardioverter-defibrillator (S-ICD) is a novel technology for the treatment of sudden cardiac death. The system consists of a pulse generator implanted in the left axillary position and a single subcutaneous lead for detection and delivery of therapy. Initial clinical trials of S-ICDs demonstrated improved safety and efficacy when compared to transvenous ICD systems, leading to their widespread approval. The main advantage of the S-ICD is the avoidance of vascular access and the complications associated with transvenous leads. Owing to limitations of S-ICDs, patients who require pacing support or antitachycardia pacing are not candidates for the device; instead, this system is currently used most commonly in young patients with previous lead malfunction, limited vascular access, or low risk for subsequent bradycardia or antitachycardia pacing. Findings from device trials support S-ICDs as a viable alternative to transvenous ICDs in certain patients, and the current limitations associated with S-ICDs are likely to be addressed in future iterations of the device, extending its indications and target patient populations.

This study evaluates and provides guidance on improving the life cycle environmental performance of dishwashing in the typical U.S. household. Typical user behaviors and recommended best practices for manual dishwashing as well as machine dishwasher use are evaluated. A sensitivity analysis shows the influence of varying grid carbon intensity, water heater type, regional water scarcity, and behaviors such as pre-rinsing and machine loading on overall results. Use-phase behaviors are observed through a small-scale laboratory study. Dishwashing following typical manual and machine practices produces 5,620 and 2,090 kg CO2e life cycle greenhouse gas (GHG) emissions respectively based on washing 4 loads (8 place settings per load) a week for 10 years. Avoiding typical behaviors like pre-rinsing and selecting heated dry can decrease life cycle GHG emissions for machine dishwashing by 3% and 11%, respectively. The running tap style of manual dishwashing results in the highest life cycle GHG emissions of the alternatives in the lab study. Manual dishwashing has the potential to have the lowest GHG emmisions (1,610 kg) when recommended behaviors are followed, less than the 1,960 kg CO2e for recommended machine dishwasher use. When life cycle water consumption burdens are evaluated, typical manual and machine dishwashing use 34,200 and 16,300 gallons respectively and these results are contextualized to regions with different water scarcity. A life cycle cost (LCC) analysis finds that machine dishwashing costs more than manual dishwashing over a 10-year lifetime even if best practices are followed. However, when a user's time spent washing is valued, machine dishwashers pay for themselves within a year of use.

A 70-year-old woman with retinitis pigmentosa experienced an epiretinal membrane (ERM) formation and a tractional retinal detachment (RD) following subretinal administration of palucorcel (CNTO 2476), a novel human umbilical tissue-derived cell-based therapy, as part of a Phase I study. The clinical course and results of a histologic examination of the ERM, which was peeled during surgery to repair the RD, are described here. In this open-label, first-in-human, Phase I study (NCT00458575), two of seven subjects developed RD, with an ERM formation reported in a woman receiving a targeted dose of 3.0×10 palucorcel administered via a transvitreal route. A sample of the ERM was retained for analysis following the ERM peeling procedure. Clinical outcomes and ERM histology, based on immunocytochemistry analyses and fluorescence in situ hybridization (FISH) staining, were evaluated. We first noted the RD and formation of the ERM at 26 days after palucorcel administration. The ERM was cellular and contained multiple cell types, including Müller glial cells, immune cells, neurites, retinal pigment epithelial cells, and palucorcel. The majority of cells were not actively dividing. FISH staining showed a subset of Y chromosome-positive cells in the ERM from this woman, supporting the presence of palucorcel (derived from umbilical cord tissue of male neonate). Palucorcel did not differentiate into Müller glia, immune cells, neurites, or retinal pigment epithelial cells. The development of an ERM containing both subject (self) cells and palucorcel suggests that palucorcel egress in the vitreal cavity after retinotomy may contribute to ERM formation and RD and that an alternative delivery method will be required before further studies are conducted. Subsequent clinical research using alternative subretinal delivery methods for palucorcel in other indications suggests that membrane development does not occur when palucorcel is delivered without retinal perforation.

This study explored the relationship between symptoms of rapid eye movement sleep behaviour disorder, thermoregulation and sleep in Parkinson's Disease. The study group comprised 12 patients with Parkinson's Disease and 11 healthy age-matched controls. We investigated markers of thermoregulation (core-body temperature profile), circadian rhythm (locomotor actigraphy) and sleep (polysomnography). The mesor (the mean value around which the core temperature rhythm oscillates) of the core-body temperature in patients with Parkinson's Disease was significantly lower than that of controls. In addition, the nocturnal fall in CBT (the difference between the mesor and the nadir temperature) was also significantly reduced in PD patients relative to controls. Furthermore, in patients the reduction in the amplitude of their core-body temperature profile was strongly correlated with the severity of self-reported rapid eye movement sleep behaviour disorder symptom, reduction in the percentage of REM sleep and prolonged sleep latency. By contrast, these disturbances of thermoregulation and sleep architecture were not found in controls and were not related to other markers of circadian rhythm or times of sleep onset and offset. These findings suggest that the brainstem pathology associated with disruption of thermoregulation in Parkinson's disease may also contribute to rapid eye movement sleep behavioural disorder. It is possible that detailed analysis of the core-body temperature profile in at risk populations such as those patients with idiopathic rapid eye movement sleep behaviour disorder might help identify those who are at high risk of transitioning to Parkinson's Disease.

There is growing evidence that better outcomes are achieved when anticoagulation is managed by anticoagulation clinics rather than by family physicians. We carried out a randomized controlled trial to evaluate these 2 models of anticoagulant care. We randomly allocated patients who were expected to require warfarin sodium for 3 months either to anticoagulation clinics located in 3 Canadian tertiary hospitals or to their family physician practices. We evaluated the quality of oral anticoagulant management by comparing the proportion of time that the international normalized ratio (INR) of patients receiving warfarin sodium was within the target therapeutic range +/- 0.2 INR units (expanded therapeutic range) while they were managed in anticoagulation clinics as opposed to family physicians' care over 3 months. We measured the rates of thromboembolic and major hemorrhagic events and patient satisfaction in the 2 groups. Of the 221 patients enrolled, 112 were randomly assigned to anticoagulation clinics and 109 to family physicians. The INR values of patients who were managed by anticoagulation clinics were within the expanded therapeutic range 82% of the time versus 76% of the time for those managed by family physicians (p = 0.034). High-risk INR values (defined as being < 1.5 or > 5.0) were more commonly observed in patients managed by family physicians (40%) than in patients managed by anticoagulation clinics (30%, p = 0.005). More INR measurements were performed by family physicians than by anticoagulation clinics (13 v. 11, p = 0.001). Major bleeding events (2 [2%] v. 1 [1%]), thromboembolic events (1 [1%] v. 2 [2%]) and deaths (5 [4%] v. 6 [6%]) occurred at a similar frequency in the anticoagulation clinic and family physician groups respectively. Of the 170 (77%) patients who completed the patient satisfaction questionnaire, more were satisfied when their anticoagulant management was managed through anticoagulation clinics than by their family physicians (p = 0.001). Anticoagulation clinics provided better oral anticoagulant management than family physicians, but the differences were relatively modest.

On November 2nd 1917 Arthur Balfour, then Foreign Secretary, wrote to Lord Rothschild to say that the British Government viewed with favour the establishment in Palestine of a national home for the Jewish people. It was a statement the consequences of which have reverberated throughout the world in a crescendo of bitterness and violence ever since. It interposed a European (mainly Russian) Jewish cultural idea in an Arab land and it led eventually to the Arab-Israeli conflict. Eleven years before his declaration, Balfour had met the passionate Zionist and émigré chemist Chaim Weizmann while electioneering in Manchester. It was shortly after Uganda had been mooted as a possible homeland for the displaced Jews. Weizmann tried to explain his reasons for insisting on Jerusalem as the home of Zion. 'Suppose' he said, 'I were to offer you Paris instead of London?'. 'But, Dr Weizmann, we already have London,' Balfour replied. 'That is true, but we had Jerusalem when London was a marsh.' Balfour was visibly surprised. 'Are there many Jews who think like you?' he asked. 'I believe I speak for millions of Jews,' replied Weizmann. 'It is curious' Balfour remarked, 'The Jews I meet are quite different.' 'Mr Balfour' said Weizmann, ' You meet the wrong kind of Jews.' At the centre of Geoffrey Lewis's compelling book is the story of this encounter and the developing relationship between these two men: the Zionist and the Zealot, so different from each other, yet drawn together by forces that neither quite understood, with consequences that were to have a profound effect on the modern world.

AimsWe have previously identified neurofilament-protein-containing neurites in human epiretinal membranes (ERMs). The aim of this study was to further characterise these neurites by examining the expression of additional specific proteins in human ERMs and to correlate this expression with various retinal disease conditions.MethodsEpiretinal membranes originating from 43 patients with proliferative vitreoretinopathy (PVR), proliferative diabetic retinopathy (PDR) or with no known pathology (idiopathic epiretinal membrane; iERM) were removed during vitrectomy at varying durations after diagnosis and immediately placed in fixative. The membranes were labelled immunohistochemically with different combinations of antibodies to the proteins melanopsin, calretinin and neurofilament (to identify subclasses of ganglion cells), rod opsin (to identify rod photoreceptors), synaptophysin and synaptic vesicle glycoprotein 2A (SV2) (identifies synaptic vesicles) and vimentin (identifies glial cells).ResultsAnti-melanopsin-, anti-calretinin-, anti-neurofilament- and anti-rod-opsin-labelled neurites were routinely observed in the epiretinal membranes. Their presence did not appear to correlate with a specific disease condition or duration of the membrane. Generally neurites were observed in regions of glial cells.ConclusionsBased on the expression of selected markers for neurites, we show neurite processes in human ERMs of various aetiologies originating from rod photoreceptors and different populations of retinal ganglion cells, although there was no obvious correlation with specific disease condition. In addition, synaptophysin and SV2 labelling was observed associated with all types of neurites, indicating the presence of at least one component necessary for synaptic transmission. Our data suggest that the adult human retina retains a significant capacity for neuronal remodelling under various disease conditions.