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In all forms of hypertension, including human essential hypertension, pressure natriuresis is reset to higher blood pressures. Because human essential hypertension is a heterogeneous disease, it is likely that there are multiple neurohumoral and intrarenal causes of abnormal pressure natriuresis and increased blood pressure. Weight gain is recognized to be an important contributor to essential hypertension, although the mechanisms that link obesity with altered renal function and high blood pressure have not been fully elucidated. In obese dogs and humans, the shift of pressure natriuresis to higher blood pressures appears to be due mainly to increased tubular reabsorption, as glomerular filtration rate and renal plasma flow are increased compared with normal. Multiple causes of increased tubular reabsorption and hypertension in obesity have been postulated, including insulin resistance and hyperinsulinemia, activation of the sympathetic nervous and renin-angiotensin systems, and physical changes within the kidney itself. Support for the insulin resistance-hyperinsulinemia link between obesity and hypertension has been inferred mainly from acute and epidemiologic studies showing a correlation between insulin and blood pressure. Recent studies suggest that chronic hyperinsulinemia, comparable to that found in obesity, cannot account for obesity hypertension in dogs or humans. Activation of the sympathetic nervous system may play a role in obesity-induced hypertension, and there is evidence for a role of altered intrarenal physical forces caused by histological changes within the renal medulla. The quantitative importance of each of these abnormalities in altering renal function and raising blood pressure in obesity remains to be determined but is an important area of research for understanding human essential hypertension.

The treatment of hemolytic anemia of the newborn often requires support by compatible blood transfusions. Before the discovery of the Rh factor such blood was often only ABO compatible, and for convenience, the patient's father, who we now know is always Rh positive, was often used as the donor. We noted that the infant's hemoglobin level often fell rapidly, even with repeated transfusions. Because Rh positive cells are destroyed much more rapidly than Rh negative cells, it seemed logical to use only Rh negative blood as a means to achieve the highest blood levels for protection of the patient, and we began to do this after 1941.We have recently been able to show that the serum of severely affected infants contains free maternal anti Rh agglutinins and the infant's red cells are often completely coated with this antibody. The removal of much of the baby's blood should theoretically diminish the damage resulting from this antibody. Such reasoning lead us to try replacement transfusion as treatment for erythroblastosis. Although it is not a new procedure, to perform it in a newborn adds difficulty to an inherently difficult technic. Earlier methods employed the longitudinal sinus and a peripheral vein or a vein and an artery, requiring prolonged exposure of the infant on an operating table with resultant cold exposure. To prevent clotting, patients also received heparin with its risk of hemorrhage.The pediatrician cannot help but be attracted to the large and readily accessible vein in the umbilical cord. The development of a bland polyethylene catheter by Dr Ingraham of our neurosurgery department overcame some of the major difficulties of the exsanguination procedure. This catheter can be easily threaded through the umbilical vein into the vena cava through the ductus venosus or by-passing the ductus venosus into the portal vein. The catheter is connected to a needle and then to a three way stopcock. The first valve of the stopcock is connected by a tube to an exhaust pail. The second valve is connected to a bottle of blood and the third to a syringe. By alternate maneuvers of first removing and then putting in blood, 20 cc at a time, the infant can be gradually exsanguinated and most of its blood volume replaced with relatively little trauma. The procedure is carried out with the baby in a warm Hess bed with oxygen administration as needed. We usually use about a pint of Rh negative blood and the procedure takes an hour to an hour and a half. By actual measurement this replaces 90 to 95% of the infant's own red cells which are coated with antibody. At the end of the procedure, the infant is given calcium to overcome the alkalotic tetany that might result from the sodium citrate in the blood.In a quarter of cases, it is necessary to transfuse an infant again in the 2nd-4th week because of anemia, but we have rarely had to offer more than a simple transfusion. Infants can be discharged with the mother, sometimes before the eighth day has passed. Previously, the average period of hospitalization for infants with severe erythroblastosis requiring multiple transfusions was three weeks or more, during which time secondary infections could occur.Not every infant with erythroblastosis requires replacement transfusion and in the past year we have treated only about one in eight babies sent to us. We insist that we receive a specimen of the mother's blood to prove that the mother has Rh agglutinins which can be on the infant's Rh positive red cells. Further evaluation is based on clinical signs: anemia, jaundice, edema, and hepatosplenomegaly. The presence of these clinical signs with antibodies in the mother's circulation implies the need for immediate replacement transfusion.Even in the absence of these clinical signs, certain laboratory evidence may indicate the need for immediate treatment. If the baby's Rh positive cells are coated with antibody and the baby has free antibody in its circulation, our selected data over several years indicate that replacement transfusion should be done because such infants quite regularly develop severe symptoms within the second to fourth day of life. The absence of clinical signs and the absence of the laboratory findings suggest that the infant will do well enough without such drastic treatment.As a background for an evaluation of our present mode of therapy, we have statistics collected over the past 15 years. Before 1941, taking all of the infants sent to us, there was a 35–40% mortality. Between 1941 and 1946, with Rh negative transfusions, our mortality dropped to 30% or less. Our present data covers about 15 months of experience and 85 infants treated personally by replacement transfusions through the umbilical vein. Sixty-five are now living and well with follow ups of 3 to 15 months. A number of the surviving infants came from families where a previous infant had died of erythroblastosis. In such families the chance of a subsequent affected infant surviving is less than 10%. The survival of such children in our series was 70%. Seven patients died, but not of erythroblastosis. The causes were immaturity, tentorial tears or other factors which cannot be directly related to erythroblastosis. Seven patients died of the disease; six of these showed kernicterus.This mode of therapy has the advantage of ease and greater safety in performance. An added advantage is earlier discharge from the hospital at 7 or 8 days rather than 2 to 3 weeks. Although this is not a panacea for erythroblastosis, replacement transfusion seems to be a better method of treatment for many cases.

During a tropical cyclone, windshear can occur at Hong Kong International Airport (HKIA) owing to interactions between strong winds and the complex topography of the neighboring Lantau Island. For aviation safety, it is crucial to understand how such interactions arise under realistic but controlled meteorological conditions. In this study, we numerically simulate the turbulent airflow over Lantau Island and HKIA using OpenFOAM, an open-source platform for computational fluid dynamics. We use the platform to solve the Reynolds-averaged Navier–Stokes equations via the finite volume method of discretization. We impose a neutrally stratified atmospheric boundary layer as the upwind condition, which is initialized with a logarithmic velocity profile in three different wind directions: southerly, southeasterly and easterly. For all three directions, we find multiple high-speed ∨ -shaped jets emanating from the mountain gaps of Lantau Island, giving rise to headwind and crosswind variations along the glide paths of HKIA. However, we find that it is primarily the southerly and southeasterly winds that are the most conducive to windshear. For these two wind directions, we find that windshear is most likely to occur along the glide paths of the two existing runways because these are the closest to Lantau Island itself. The third runway, which is currently under construction, is the least likely to suffer from windshear. By showing how airflow disturbances arise from the complex topography of Lantau Island, this study contributes to safer and more efficient flight operations at HKIA.

Background Calcitonin gene-related peptide is recognized as a key player in migraine, yet the mechanisms and sites of calcitonin gene-related peptide action remain unknown. The efficacy of calcitonin gene-related peptide-blocking antibodies as preventative migraine drugs supports a peripheral site of action, such as the trigeminovasculature. Given the apparent disconnect between the importance of vasodilatory peptides in migraine and the prevailing opinion that vasodilation is an epiphenomenon, the goal of this study was to test whether vasodilation plays a role in calcitonin gene-related peptide-induced light aversive behavior in mice. Methods Systemic mean arterial pressure and light aversive behavior were measured after intraperitoneal administration of calcitonin gene-related peptide and vasoactive intestinal peptide in wild-type CD1 mice. The functional significance of vasodilation was tested by co-administration of a vasoconstrictor (phenylephrine, endothelin-1, or caffeine) with calcitonin gene-related peptide to normalize blood pressure during the light aversion assay. Results Both calcitonin gene-related peptide and vasoactive intestinal peptide induced light aversion that was associated with their effect on mean arterial pressure. Notably, vasoactive intestinal peptide caused relatively transient vasodilation and light aversion. Calcitonin gene-related peptide-induced light aversion was still observed even with normalized blood pressure. However, two of the agents, endothelin-1 and caffeine, did reduce the magnitude of light aversion. Conclusion We propose that perivascular calcitonin gene-related peptide causes light-aversive behavior in mice by both vasomotor and non-vasomotor mechanisms.

Purpose To investigate whether time to peak best-corrected visual acuity (BCVA) was predictive of magnitude of BCVA changes at study end in patients with neovascular age-related macular degeneration (nAMD) who received ranibizumab and assess whether patient baseline characteristics and on-study events were predictive of time to peak BCVA. Design Exploratory analysis of data from HARBOR ( ClinicalTrials.gov identifier, NCT00891735 ). Participants Treatment-naive patients 50 years of age or older with subfoveal nAMD. Methods Data by ranibizumab dose were pooled; data by dosing schedule (pro re nata [PRN] and monthly) were evaluated separately. Time to peak BCVA was the monthly evaluation at which the patient’s greatest gain in Early Treatment Diabetic Retinopathy Study (ETDRS) letters from baseline was achieved. Early peakers achieved peak BCVA between day 7 and month 6; late peakers achieved peak BCVA between months 7 and 12, months 13 and 18, and months 19 and 24. Variables evaluated for effect of time to peak BCVA included baseline demographic and clinical characteristics, presence of persistent subretinal fluid (SRF) or intraretinal fluid (IRF), and on-study events (atrophy status, fibrosis, retinal pigment epithelium tears). Main Outcome Measures Time to peak BCVA and its predictive value for magnitude of BCVA changes and BCVA at month 24 (study end). Results Most patients reached peak BCVA after more than 6 months of treatment: 64% in the PRN group (301/474) and 70% in the monthly groups (327/469). Thirty-six percent and 30% of patients, respectively, peaked early, and 64% and 70%, respectively, peaked late. At month 24, early peakers on average lost vision (PRN, −1.6 ETDRS letters; monthly, −1.9 ETDRS letters). By contrast, late peakers achieved significantly better vision gains from baseline (PRN, 8.5–17.7 ETDRS letters; monthly, 10.1–18.7 ETDRS letters). No differences were found in patient characteristics, persistent SRF or IRF, or on-study events to account for the observed different outcomes between early and late peakers. Conclusions In most treatment-naive patients with nAMD, vision gains were achieved at a slower rate (>6 months), and a slower response was associated with better vision outcomes after 24 months of ranibizumab. These findings suggest that continued treatment may result in greater vision improvements when consistent anti–vascular endothelial growth factor therapy is maintained over a longer period.

Purpose This work was to establish an uncomplicated tumor control probability (UTCP) model using hepatocellular carcinoma (HCC) stereotactic body radiation therapy (SBRT) clinical data in our institution. The model was then used to analyze the current dose prescription method and to seek the opportunity for improvement. Methods and Materials A tumor control probability (TCP) model was generated based on local clinical data using the maximum likelihood method. A UTCP model was then formed by combining the established TCP model with the normal tissue complication probability model based on the study by Dawson et al. The authors investigated the dependence of maximum achievable UTCP on planning target volume equivalent uniform dose (EUD) at various ratio between planning target volume EUD and normal liver EUD (T/N EUD ratios). A new term uncomplicated tumor control efficiency (UTCE) was also introduced to analyze the outcome. A UTCE value of 1 implied that the theoretical maximum UTCP for the corresponding T/N EUD ratio was achieved. Results The UTCE of the HCC SBRT patients based on the current dose prescription method was found to be 0.93 ± 0.05. It was found that the UTCE could be increased to 0.99 ± 0.03 by using a new dose prescription scheme, for which the UTCP could be maximized while keeping the normal tissue complication probability value smaller than 5%. Conclusions The dose prescription method of the current HCC SBRT in our institution was analyzed using a UTCP model established based on local clinical data. It was shown that there could be a potential to increase the prescription dose of HCC SBRT. A new dose prescription scheme was proposed to achieve better UTCP. Additional clinical trials would be required to validate the proposed dose prescription scheme in the future.

Purpose To evaluate disease activity–free intervals of patients with neovascular age-related macular degeneration (nAMD) in the pHase III, double-masked, multicenter, randomized, Active treatment-controlled study of the efficacy and safety of 0.5 mg and 2.0 mg Ranibizumab administered monthly or on an as-needed Basis (PRN) in patients with subfoveal neOvasculaR age-related macular degeneration (HARBOR) to determine whether duration of response to previous treatment with ranibizumab informs future disease activity and need for subsequent injections. Design Retrospective subgroup analysis of the phase 3 HARBOR study ( clinicaltrials.gov identifier, NCT00891735 ). Participants Patients from the ranibizumab 0.5 mg pro re nata arm of the phase 3 HARBOR clinical trial who received all 3 loading injections and missed no more than 1 study visit (N = 217). Methods A disease activity–free interval was defined as a consecutive period in months when treatment was not required because the patient did not meet protocol retreatment criteria. Percentage of disease activity–free eyes at the next 1 and 2 months after a first disease activity–free interval of ≥2, ≥3, ≥4, ≥5, and ≥6 months was evaluated. Additionally, duration that eyes remained untreated after disease activity–free intervals was evaluated by Kaplan-Meier estimates. Main Outcome Measures Key outcome measures included duration of the first treatment-free interval of ≥2, ≥3, ≥4, ≥5, and ≥6 months achieved by each patient; mean number of additional months patients remained treatment free after a treatment-free interval; and percentage of eyes requiring treatment within 2 months after each treatment-free interval. Results Percentage of eyes requiring retreatment the month after a treatment-free interval of ≥2, ≥3, ≥4, ≥5, and ≥6 months was 60% (90/151), 33% (33/100), 26% (20/77), 36% (24/66), and 19% (9/48), respectively. Percentage of eyes requiring retreatment within 2 months after a treatment-free interval of ≥2, ≥3, ≥4, ≥5, and ≥6 months was 73% (109/149), 53% (53/100), 53% (40/75), 47% (30/64), and 43% (20/46), respectively. After treatment-free intervals of ≥2, ≥3, ≥4, ≥5, and ≥6 months, mean (standard error of the mean) additional time treatment free was 1.3 months (0.17 month), 2.4 months (0.33 month), 2.9 months (0.44 month), 3.2 months (0.50 month), and 4.0 months (0.60 month), respectively. Conclusions Longer treatment-free intervals may indicate longer future disease-free intervals; however, this association varies. Thus, although longer intervals suggest greater likelihood of not needing retreatment within 1 to 2 months, regular assessment is warranted owing to the unpredictability of nAMD disease activity.

Mobilities has become a keyword in the agendas of policy makers and the decisions of individuals, including young people. Hong Kong as a city long defined as a hub of cross-border flows has...

Background To determine whether aflibercept (Eylea; Regeneron Pharmaceuticals, Inc., Tarrytown, NY) could continue to extend the macular edema free interval in patients on a treat and extend (TAE) with non-ischemic central retinal vein occlusions (CRVOs) previously treated with ranibizumab (Lucentis; Genentech, Inc., South San Francisco, CA) or bevacizumab (Avastin; Genentech, Inc., South San Francisco, CA) in the second year. Methods Twenty patients with macular edema secondary to non-ischemic CRVOs previously treated with ranibizumab or bevacizumab were prospectively treated with intravitreal aflibercept injection (IAI) using a TAE dosing regimen. Injection frequencies were extended 2 weeks if there were no signs of disease activity on OCT or change in visual acuity. In the second year of the study, patients who have recurrences of macular edema could be re-challenged with a longer treatment interval under the following criterion: absence of any macular edema on three consecutive visits with the same treatment interval. Results Twenty patients had an average duration of a CRVO for 22 months (range 7–90) and averaged an anti-VEGF treatment every 42 days (range 28–60 days). The macular edema free interval increased from 38 to 75 days when switched to aflibercept (p = 0.000003) at month 24. There was an average increase of 37 days (median 34 days; range 0–91 days) in the macular edema free interval with aflibercept. At the month 24 visit, 50% (8/16) went > 12 weeks with a macular edema free interval between IAI. There was an improvement in vision (+ 8 ETDRS letters, p = 0.006) and decreased retinal thickness (158 µm, p = 0.00003) with aflibercept treatment at month 24. Conclusions The 2-year results of the NEWTON study demonstrated the sustained benefits of a TAE dosing regimen with aflibercept in patients with chronic CRVOs. The visual acuity gains and anatomic improvements observed at year one were maintained through month 24 with less visits and treatments. This may help minimize the treatment burden in patients with recurrent macular edema secondary to non-ischemic CRVO. Trial Registration ClinicalTrials.gov, NCT01870427, Registered June 6, 2013, https://clinicaltrials.gov/ct2/show/NCT01870427?cond=NEWTON&rank=1. Presented at the RETICON 2017: The Retina Congress with Live Surgery, Chennai, India-April 2017.

Objective: To retrospectively analyze the clinical impact on stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma (HCC) located at lung–liver boundary due to the use of Acuros XB algorithm (AXB) in replacement of anisotropic analytical algorithm (AAA). Methods: 23 SBRT volumetric modulated arc therapy (VMAT) plans for HCC located at lung–liver boundary were calculated using AAA and AXB respectively with the same treatment parameters. The dose–volume data of the planned target volumes (PTVs) were compared. A published tumour control probability (TCP) model was used to calculate the effect of dosimetric difference between AAA and AXB on tumour control probability. Results: For dose calculated by AXB (Dose to medium), the D95% and D98% of the PTV were on average 2.4 and 3.1% less than that calculated by AAA. For dose calculated by AXB (dose to water), the D95% and D98% of the PTV were on average 1.8%, and 2.7% less than that calculated by AAA. Up to 5% difference in D95% and 8% difference in D98% were observed in the worst cases. The significant decrease in D95% calculated by AXB compared to AAA could result in a % decrease in 2 year TCP up to 8% in the worst case (from 46.8 to 42.9%). Conclusion: The difference in dose calculated by AAA and AXB could lead to significant difference in TCP for HCC SBRT located at lung–liver boundary region. Advances in knowledge: The difference in calculated dose and tumour control probability for HCC SBRT between AAA and AXB algorithm at lung–liver boundary region was compared.

Purpose To report a case of a hemi-retinal vein occlusion (HRVO) in the setting of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Observations A 32-year-old healthy male presented with a paracentral scotoma, retinal hemorrhages, and dilated and tortuous retinal vessels inferiorly in the right eye. He was diagnosed with HRVO in the setting of recent SARS-CoV-2 infection. Conclusions and importance Venous thromboembolic complications and coagulation abnormalities have been widely reported in association with SARS-CoV-2 infection. We highlight this case to raise awareness that a retinal vein occlusion in an otherwise healthy, young patient may be a potential manifestation of the thromboinflammatory state associated with SARS-CoV-2 infection.

BackgroundThe COVID-19 pandemic threatens access to sexual and reproductive health services. With global health emergencies, there is often a total reversal of priorities and access to sexual and reproductive health services may become challenging. The aim of this study was to establish the problems related to sexual and reproductive health among Ugandan youths during the COVID-19 lockdown. MethodsThis was an online cross-sectional study carried out from April 2020 to May 2020 in Uganda. An online questionnaire was used and participants aged 18years to 30 years recruited using the snowballing approach. The statistical analysis was done using STATA version 14.2.Results Out of 724 participants, 203 (28%) reported not having information and/or education concerning sexual and reproductive health (SRH). About a quarter of the participants (26.9%, n=195) reported not having testing and treatment services of sexually transmitted infections available during the lockdown. Lack of transport means was the commonest (68.7%) limiting factor to access to SRH services during the lockdown followed by the long distance from home to SRH facility (55.2%), high cost of services (42.2%) and curfew (39.1%). Sexually transmitted infections were the commonest (40.4%) problem related to SRH during the lockdown followed by unwanted pregnancy (32.4%) and sexual abuse (32.4%). The multivariate regression analysis shows that problems were more prevalent among the co-habiting youth [APR: 2.3 (1.6 - 3.29), pConclusionsThe findings of this study show that Ugandan youths have accessing SRH information and services during the COVID-19 lockdown. Cohabiting and unemployed participants were the most affected. Lack of transport means and high cost of services were the major limiting factors to access SRH services among the youths. The findings call for concerted efforts from the Uganda government and international non-governmental organisations to ensure access and availability of SRH services for Ugandan youths during the COVID-19 lockdown.

Though many service members will not directly seek mental health care due to stigma and other factors, they may interact with the healthcare system in other ways including contact with first responders, nurses and allied health care professionals. However, little attention has been spent in this regard on the educational needs of these professionals whose contact with service members and veterans may provide the opportunity to assist veterans in need with overcoming barriers to accessing mental health care. This qualitative study investigates the educational training needs of first responders and health care professionals in contact with military families and trauma survivors to determine whether, and what type, of additional training is needed. A sample of 42 first responders and health care professionals including emergency medical technicians, police officers, fire fighters, speech language pathologists, occupational therapists, physical therapists, and nurses, were recruited to participate in one of six focus groups. Sessions were audio-taped and transcribed verbatim. Data analysis was guided by a thematic analysis approach. Thematic analyses suggest there is a significant knowledge gap with unmet educational needs of these professionals such as information on the invisible wounds of war, military culture, and screening and referring patients who present symptoms falling outside professionals' scope of practice. Findings point to a need and desire for more robust education for first responders and health care providers around mental health concerns of military populations, including topics such as trauma, military culture, and screening tools. Efforts to develop curricula addressing these concerns are warranted.

James L. Januzzi, Jr, MD, FACC Luis C. Afonso, MBBS, FACC Brendan Everett, MD, FACC Adrian F. Hernandez, MD, MHS, FACC William Hucker, MD, PhD Hani Jneid, MD, FACC Dharam Kumbhani, MD, SM, FACC Joseph Edward Marine, MD, FACC Pamela Bowe Morris, MD, FACC Robert N. Piana, MD, FACC Karol E.

James L. Januzzi, Jr, MD, FACC Luis C. Afonso, MBBS, FACC Brendan Everett, MD, FACC Adrian F. Hernandez, MD, MHS, FACC William Hucker, MD, PhD Hani Jneid, MD, FACC Dharam Kumbhani, MD, SM, FACC Joseph Edward Marine, MD, FACC Pamela Bowe Morris, MD, FACC Robert N. Piana, MD, FACC Karol E.

James L. Januzzi, Jr, MD, FACC Luis C. Afonso, MBBS, FACC Brendan Everett, MD, FACC Adrian F. Hernandez, MD, MHS, FACC William Hucker, MD, PhD Hani Jneid, MD, FACC Dharam Kumbhani, MD, SM, FACC Joseph Edward Marine, MD, FACC Pamela Bowe Morris, MD, FACC Robert N. Piana, MD, FACC Karol E.

PURPOSE Use standardized methods to determine how assessment of protective value of radiation-protective garments changes under conditions employing standard beam qualities, scatter-mimicking primary beams, and a modified Hp (10) measurement. METHODS The shielding properties of radiation-protective garments depend on the spectrum of beam energies striking the garment and the attenuation properties of materials used to construct the garment, including x-ray fluorescence produced by these materials. In this study the primary beam spectra employed during clinical interventional radiology and cardiology procedures (clinical primary beams, CPB) were identified using radiation dose structured reports (RDSR) and fluoroscope log data. Monte Carlo simulation was used to determine the scattered radiation spectra produced by these CPB during typical clinical application. For these scattered spectra, scatter-mimicking primary beams (SMPB) were determined using numerical optimization-based spectral reconstruction that adjusted kV and filtration to produce the SMPB that optimally matched the scattered spectrum for each CPB. The penetration of a subset of SMPB through four radiation-protective garments of varying compositions and nominal thicknesses was measured using a geometry specified by the International Electrotechnical Commission (IEC). The diagnostic radiological index of protection (DRIP), which increases with increasing penetration through a garment, was calculated using these measurements. Penetration through the same garments was measured for standard beams specified by the American Society of Testing and Materials (ASTM). Finally, 10 mm of PMMA was affixed to the inside of each garment and the DRIP remeasured in this configuration to simulate Hp (10). RESULTS The SMPB based on actual CPB were in general characterized by lower kV (range 60-76) and higher half-value layer (HVL, range 3.44-4.89 mm Al) than standard beam qualities specified by ASTM (kV range 70-85; HVL range 3.4-4.0 mm Al). A lead garment of nominal thickness 0.5 mm (D) had a DRIP of 0.8%, two lead-free garments of 0.5 mm nominal thickness had DRIPs of 1.2% (A) and 2.2% (B), and a lead-free bilayer (C) had a DRIP of 1.4%. When standard beam qualities specified by the ASTM were used, the DRIP for D was 2.2%, 175% higher than the DRIP measured using SMPB, and for A, B, and C was 2.8%, 3.2%, and 2.9%, respectively. This was 133%, 45%, and 107% higher than the DRIP measured using SMPB. Differences between the DRIP of lead-alternative garments and the lead garment were reduced when measured with 10 mm of PMMA. Using this method, the measured DRIPs were 2.2% (A), 3.1% (B), 2.5% (C), and 2.3% (D). CONCLUSIONS Penetration of radiation through radiation-protective garments depended strongly on the methods and X-ray spectra used for evaluation. The DRIP was higher (i.e., protective value was lower) for lead-alternative garments than for lead garments in this evaluation. The DRIP was lower for all garments when SMPB based on actual clinical beam quality data were used to measure penetration compared to ASTM standard beams. Differences in penetration between lead-alternative and lead garments were less when the DRIP was measured with 10 mm of PMMA between the garment and the chamber.

Objective.The feasibility of magnetic-field-modulated radiotherapy (MagMRT) with an MR-LINAC was investigated by studying the effects of dose enhancement and reduction using a transverse magnetic field with a longitudinal gradient applied along a photon radiation beam.Approach.Geant4 simulation toolkit was used to perform Monte Carlo simulations on a water phantom with the energy spectrum of a 7 MV flattening-filter-free photon beam from an Elekta Unity system as the source of radiation. Linear magnetic field gradients with magnitudes ranged from 1 to 6 T cm-1and spatial extents of 1-3 cm were used to study the dependence of dose modulation on these two parameters. The effects of radiation field size and the ability of dose modulation through optimizing the waveform of magnetic field variation were also explored.Main results.Our results show that dose enhancement and reduction can be achieved by applying a transverse magnetic field with a longitudinal field gradient along a photon beam. The steeper the gradient, the more prominent is the effect. A dose enhancement of 33% and a dose reduction of 22% are found for a magnetic gradient of 6 T cm-1and -6 T cm-1respectively. The spatial extent of the dose modulation effect which is greater than 3% is found to be around 1-2 cm. Both the dose enhancement and reduction effects are independent of the radiation field sizes, but they exhibit different behaviors with the spatial extents of the gradient. Multiple locations of dose enhancement and reduction can be produced by modulating the waveform of the magnetic field variation along the radiation beam, demonstrating a vast degree of freedom in the modulation aspect of MagMRT.Significance.MagMRT is a conceptually feasible and promising new radiotherapy modulation technique along the direction of the radiation beam.

Patient-derived tumor xenograft (PDTX) mouse models were used to discover new therapies for naive and drug resistant BRAFV600E -mutant melanoma. Tumor histology, oncogenic protein expression, and antitumor activity were comparable between patient and PDTX-matched models thereby validating PDTXs as predictive preclinical models of therapeutic response in patients. PDTX models responsive and non-responsive to BRAF/MEK standard of care (SOC) therapy were used to identify efficacious combination therapies. One such combination includes a CDK4/6 inhibitor that blocks cell cycle progression. The rationale for this is that the retinoblastoma protein (pRb) is 95% wildtype in BRAF mutant melanoma. We discovered that 77/77 stage IV metastatic melanoma tissues were positive for inactive phosphorylated pRb (pRb-Ser780). Rb is hyperphosphorylated and inactivated by CDK4/6:cyclin D1 and when restored to its hypophosphorylated active form blocks cell cycle progression. The addition of a CDK4/6 inhibitor to SOC therapy was superior to SOC. Importantly, triple therapy in an upfront treatment and salvage therapy setting provided sustained durable response. We also showed that CDK4/6 blockade resensitized drug resistant melanoma to SOC therapy. Durable response was associated with sustained suppression of pRb-Ser780. Thus, reactivation of pRb may prove to be a clinical biomarker of response and the mechanism responsible for durable response. In light of recent clinical trial data using this triple therapy against BRAFV600E -mutant melanoma, our findings demonstrating superior and prolonged durable response in PDTX models portend use of this therapeutic strategy against naive and SOC resistant BRAFV600E -mutant metastatic melanoma coupled with pRB-Ser780 as a biomarker of response.

Oral and maxillofacial surgeons have been providing safe anesthesia to their patients using the anesthesia team model; this has allowed access to care for patients that have significant anxiety. The AAOMS strives to maintain the excellent safety record of the anesthesia team model by creating simulation programs in anesthesia, regularly updating the office anesthesia evaluation program, convening anesthesia safety conferences and strengthening the standards in our training programs. Through these efforts, our delivery of anesthesia to our patients will remain safe and effective.

BackgroundThe United States Department of Agriculture (USDA) National Plant Germplasm System (NPGS) sorghum core collection contains 3011 accessions randomly selected from 77 countries. Genomic and phenotypic characterization of this core collection is necessary to encourage and facilitate its utilization in breeding programs and to improve conservation efforts. In this study, we examined the genome sequences of 318 accessions belonging to the NPGS Sudan sorghum core set, and characterized their agronomic traits and anthracnose resistance response.ResultsWe identified 183,144 single nucleotide polymorphisms (SNPs) located within or in proximity of 25,124 annotated genes using the genotyping-by-sequencing (GBS) approach. The core collection was genetically highly diverse, with an average pairwise genetic distance of 0.76 among accessions. Population structure and cluster analysis revealed five ancestral populations within the Sudan core set, with moderate to high level of genetic differentiation. In total, 171 accessions (54%) were assigned to one of these populations, which covered 96% of the total genomic variation. Genome scan based on Tajima’s D values revealed two populations under balancing selection. Phenotypic analysis showed differences in agronomic traits among the populations, suggesting that these populations belong to different ecogeographical regions. A total of 55 accessions were resistant to anthracnose; these accessions could represent multiple resistance sources. Genome-wide association study based on fixed and random model Circulating Probability (farmCPU) identified genomic regions associated with plant height, flowering time, panicle length and diameter, and anthracnose resistance response. Integrated analysis of the Sudan core set and sorghum association panel indicated that a large portion of the genetic variation in the Sudan core set might be present in breeding programs but remains unexploited within some clusters of accessions.ConclusionsThe NPGS Sudan core collection comprises genetically and phenotypically diverse germplasm with multiple anthracnose resistance sources. Population genomic analysis could be used to improve screening efforts and identify the most valuable germplasm for breeding programs. The new GBS data set generated in this study represents a novel genomic resource for plant breeders interested in mining the genetic diversity of the NPGS sorghum collection.

The neural circuits responsible for behavior remain largely unknown. Previous efforts have reconstructed the complete circuits of small animals, with hundreds of neurons, and selected circuits for larger animals. Here we (the FlyEM project at Janelia and collaborators at Google) summarize new methods and present the complete circuitry of a large fraction of the brain of a much more complex animal, the fruit fly Drosophila melanogaster. Improved methods include new procedures to prepare, image, align, segment, find synapses, and proofread such large data sets; new methods that define cell types based on connectivity in addition to morphology; and new methods to simplify access to a large and evolving data set. From the resulting data we derive a better definition of computational compartments and their connections; an exhaustive atlas of cell examples and types, many of them novel; detailed circuits for most of the central brain; and exploration of the statistics and structure of different brain compartments, and the brain as a whole. We make the data public, with a web site and resources specifically designed to make it easy to explore, for all levels of expertise from the expert to the merely curious. The public availability of these data, and the simplified means to access it, dramatically reduces the effort needed to answer typical circuit questions, such as the identity of upstream and downstream neural partners, the circuitry of brain regions, and to link the neurons defined by our analysis with genetic reagents that can be used to study their functions.Note: In the next few weeks, we will release a series of papers with more involved discussions. One paper will detail the hemibrain reconstruction with more extensive analysis and interpretation made possible by this dense connectome. Another paper will explore the central complex, a brain region involved in navigation, motor control, and sleep. A final paper will present insights from the mushroom body, a center of multimodal associative learning in the fly brain.

Due to technological advances in electron microscopy (EM) and deep learning, it is now practical to reconstruct a connectome, a description of neurons and the connections between them, for significant volumes of neural tissue. The limited scope of past reconstructions meant they were primarily used by domain experts, and performance was not a serious problem. But the new reconstructions, of common laboratory creatures such as the fruit fly Drosophila melanogaster, upend these assumptions. These natural neural networks now contain tens of thousands of neurons and tens of millions of connections between them, with yet larger reconstructions pending, and are of interest to a large community of non-specialists. This requires new tools that are easy to use and efficiently handle large data. We introduce neuPrint to address these data analysis challenges. neuPrint is a database and analysis ecosystem that organizes connectome data in a manner conducive to biological discovery. In particular, we propose a data model that allows users to access the connectome at different levels of abstraction primarily through a graph database, neo4j, and its powerfully expressive query language Cypher. neuPrint is compatible with modern connectome reconstruction workflows, providing tools for assessing reconstruction quality, and offering both batch and incremental updates to match modern connectome reconstruction flows. Finally, we introduce a web interface and programmer API that targets a diverse user skill set. We demonstrate the effectiveness and efficiency of neuPrint through example database queries.

Ovarian cystic teratomas consist of germ cell tumors. They appear in female patients aged 20-40 years, comprising 15% of all ovarian neoplasms.

This study examines changes in the cultural policy in Hong Kong amid the transformations of political economy in the 1990s, following the handover in 1997, and under the administration of three Chief Executives (and their teams) up to 2015. When reviewing the literature on cultural policies in Hong Kong, this study examines the interaction the policies have with the political-economic development in Hong Kong (within the scope of this study) and subsequently explores changes in the principles of the policies. In other words, this study attempts to understand the conditions under which cultural policies were formulated in Hong Kong (the conditions of the production of local culture). The analytical framework of this study is based on two observations of the political and social changes occurring in Hong Kong (1997–2015): (1) changes in the government’s governance attitude since the handover in 1997, and (2) a series of economic blows Hong Kong has endured since 1998. Differing from the ‘descriptive literature’ defined by Schuster, this study understands that these changes are a result of the influence of a postcolonial state and neo-liberalism on public policy formulation. It is argued that the Hong Kong cultural policy framework has shifted from checks-and-balances towards centralised market orientation.

Purpose: To evaluate the sensitivity of the diagnostic radiological index of protection (DRIP), used to quantify the protective value of radioprotective garments, to procedural factors in fluoroscopy in an effort to determine an appropriate set of scatter-mimicking primary beams to be used in measuring the DRIP. Methods: Monte Carlo simulations were performed to determine the shape of the scattered x-ray spectra incident on the operator in different clinical fluoroscopy scenarios, including interventional radiology and interventional cardiology (IC). Two clinical simulations studied the sensitivity of the scattered spectrum to gantry angle and patient size, while technical factors were varied according to measured automatic dose rate control (ADRC) data. Factorial simulations studied the sensitivity of the scattered spectrum to gantry angle, field of view, patient size, and beam quality for constant technical factors. Average energy (Eavg) was the figure of merit used to condense fluence in each energy bin to a single numerical index. Results: Beam quality had the strongest influence on the scattered spectrum in fluoroscopy. Many procedural factors affect the scattered spectrum indirectly through their effect on primary beam quality through ADRC, e.g., gantry angle and patient size. Lateral C-arm rotation, common in IC, increased the energy of the scattered spectrum, regardless of the direction of rotation. The effect of patient size on scattered radiation depended on ADRC characteristics, patient size, and procedure type. Conclusions: The scattered spectrum striking the operator in fluoroscopy is most strongly influenced by primary beam quality, particularly kV. Use cases for protective garments should be classified by typical procedural primary beam qualities, which are governed by the ADRC according to the impacts of patient size, anatomical location, and gantry angle.

OBJECTIVE Extensive research supports the use of prolonged exposure (PE) and cognitive processing therapy (CPT), for posttraumatic stress disorder (PTSD) in veterans and service members. PE and CPT have been disseminated nationally across the Department of Veterans Affairs (VA) facilities. Many service members and veterans receive care outside the VA where access to these gold standard psychotherapies can be limited. This paper presents a novel program developed to train community providers in the use of PE and CPT and their application to veterans with PTSD through the use of a medium-touch approach to consultation. METHOD Four 2-day trainings (2 in PE, 2 in CPT) were delivered to a total of 170 participants over an 8-month period. A subset of approximately 10 providers per training (n = 42) received 6 months of weekly, group phone consultation following the 2-day training. All providers were assessed pre- and posttraining, as well as 3 and 6 months after their training. Outcomes for the training workshop alone and the training plus 6 months of consultation were compared. RESULTS While participant knowledge, t = -22.57, p < .001 and comfort (χ² = 74.00, p < .001) with PE and CPT significantly increased immediately following the 2-day training, those who received consultation were more likely to implement (χ² = 20.88, p < .001) and either complete or be close to completing PE or CPT with patients (χ² = 20.57, p < .001) 6 months following training. CONCLUSIONS Despite some limitations, these preliminary data support that consultation is an important component to include in PTSD therapy training and implementation in the community. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Extracting a connectome from an electron microscopy (EM) data set requires identification of neurons and determination of connections (synapses) between neurons. As manual extraction of this information is very time-consuming, there has been extensive research efforts to automatically segment the neurons to help guide and eventually replace manual tracing. Until recently, there has been comparatively little research on automatic detection of the actual synapses between neurons. This discrepancy can, in part, be attributed to several factors: obtaining neuronal shapes is a prerequisite for the first step in extracting a connectome, manual tracing is much more time-consuming than annotating synapses, and neuronal contact area can be used as a proxy for synapses in determining connections. However, recent research has demonstrated that contact area alone is not a sufficient predictor of a synaptic connection. Moreover, as segmentation improved, we observed that synapse annotation consumes a more significant fraction of overall reconstruction time (upwards of 50% of total effort). This ratio will only get worse as segmentation improves, gating the overall possible speed-up. Therefore, we address this problem by developing algorithms that automatically detect presynaptic neurons and their postsynaptic partners. In particular, presynaptic structures are detected using a U-Net convolutional neural network (CNN), and postsynaptic partners are detected using a multilayer perceptron (MLP) with features conditioned on the local segmentation. This work is novel because it requires minimal amount of training, leverages advances in image segmentation directly, and provides a complete solution for polyadic synapse detection. We further introduce novel metrics to evaluate our algorithm on connectomes of meaningful size. When applied to the output of our method on EM data from Drosphila, these metrics demonstrate that a completely automatic prediction can be used to effectively characterize most of the connectivity correctly.

Design Flows. Logic Synthesis. Power Analysis and Optimization from Circuit to Register Transfer Levels. Equivalence checking. Digital Layout - Placement. Static Timing Analysis. Structured Digital Design. Routing. Exploring Challenges of Libraries for Electronic Design. Design Closure. Tools for Chip-Package Codesign. Design Databases. FPGA Synthesis and Physical Design. Simulation of Analog and Radio Frequency Circuits and Systems. Simulation and Modeling for Analog and Mixed-Signal Integrated Circuits. Layout Tools for Analog ICs and Mixed-Signal SoCs. Design Rule Checking. Resolution Enhancement Technology and Mask Data Preparation. Design for Manufacturability in the Nanometer Era. Power Supply Network Design and Analysis. Noise Considerations in Digital ICs. Layout Extraction. Mixed-Signal Noise Coupling in System-on-Chip Design: Modeling, Analysis and Validation. Process Simulation. Device Modeling: From Physics to Electrical Parameter Extraction. High-Accuracy Parasitic Extraction.

New reconstruction techniques are generating connectomes of unprecedented size. These must be analyzed to generate human comprehensible results. The analyses being used fall into three general categories. The first is interactive tools used during reconstruction, to help guide the effort, look for possible errors, identify potential cell classes, and answer other preliminary questions. The second type of analysis is support for formal documents such as papers and theses. Scientific norms here require that the data be archived and accessible, and the analysis reproducible. In contrast to some other ``omic'' fields such as genomics, where a few specific analyses dominate usage, connectomics is rapidly evolving and the analyses used are often specific to the connectome being analyzed. These analyses are typically performed in a variety of conventional programming language, such as Matlab, R, Python, or C++, and read the connectomic data either from a file or through database queries, neither of which are standardized. In the short term we see no alternative to the use of specific analyses, so the best that can be done is to publish the analysis code, and the interface by which it reads connectomic data. A similar situation exists for archiving connectome data. Each group independently makes their data available, but there is no standardized format and long-term accessibility is neither enforced nor funded. In the long term, as connectomics becomes more common, a natural evolution would be a central facility for storing and querying connectomic data, playing a role similar to the National Center for Biotechnology Information for genomes. The final form of analysis is the import of connectome data into downstream tools such as neural simulation or machine learning. In this process, there are two main problems that need to be addressed. First, the reconstructed circuits contain huge amounts of detail, which must be intelligently reduced to a form the downstream tools can use. Second, much of the data needed for these downstream operations must be obtained by other methods (such as genetic or optical) and must be merged with the extracted connectome.

The stimulus to create this document was the recognition that ionizing radiation-guided cardiovascular procedures are being performed with increasing frequency, leading to greater patient radiation exposure and, potentially, to greater exposure for clinical personnel. Although the clinical benefit of these procedures is substantial, there is concern about the implications of medical radiation exposure. The American College of Cardiology leadership concluded that it is important to provide practitioners with an educational resource that assembles and interprets the current radiation knowledge base relevant to cardiovascular procedures. By applying this knowledge base, cardiovascular practitioners will be able to select procedures optimally, and minimize radiation exposure to patients and to clinical personnel. Optimal Use of Ionizing Radiation in Cardiovascular Imaging: Best Practices for Safety and Effectiveness is a comprehensive overview of ionizing radiation use in cardiovascular procedures and is published online. To provide the most value to our members, we divided the print version of this document into 2 focused parts. Part I: Radiation Physics and Radiation Biology addresses the issue of medical radiation exposure, the basics of radiation physics and dosimetry, and the basics of radiation biology and radiation-induced adverse effects. Part II: Radiological Equipment Operation, Dose-Sparing Methodologies, Patient and Medical Personnel Protection covers the basics of operation and radiation delivery for the 3 cardiovascular imaging modalities (x-ray fluoroscopy, x-ray computed tomography, and nuclear scintigraphy) and will be published in the next issue of the Journal.

The stimulus to create this document was the recognition that ionizing radiation-guided cardiovascular procedures are being performed with increasing frequency, leading to greater patient radiation exposure and, potentially, to greater exposure to clinical personnel. While the clinical benefit of these procedures is substantial, there is concern about the implications of medical radiation exposure. ACC leadership concluded that it is important to provide practitioners with an educational resource that assembles and interprets the current radiation knowledge base relevant to cardiovascular procedures. By applying this knowledge base, cardiovascular practitioners will be able to select procedures optimally, and minimize radiation exposure to patients and to clinical personnel. "Optimal Use of Ionizing Radiation in Cardiovascular Imaging - Best Practices for Safety and Effectiveness" is a comprehensive overview of ionizing radiation use in cardiovascular procedures and is published online. To provide the most value to our members, we divided the print version of this document into 2 focused parts. "Part I: Radiation Physics and Radiation Biology" addresses radiation physics, dosimetry and detrimental biologic effects. "Part II: Radiologic Equipment Operation, Dose-Sparing Methodologies, Patient and Medical Personnel Protection" covers the basics of operation and radiation delivery for the 3 cardiovascular imaging modalities (x-ray fluoroscopy, x-ray computed tomography, and nuclear scintigraphy). For each modality, it includes the determinants of radiation exposure and techniques to minimize exposure to both patients and to medical personnel.

A Toure Offianan1, Louis K Penali1, MA Coulibaly1, NL Tiacoh1, AAB Ako1, EG Adji1, B Coulibaly1, D Koffi1, D Sarr2, R Jambou3, M Kone41Department of Malariology, Institut Pasteur of Côte d’Ivoire, 2Department of Infectious Diseases, University of Georgia, Athens, GA, 3Department of Immunology, Institut Pasteur of Madagascar, Tananarive, Madagascar, 4UFR Sciences Pharmaceutiques et Biologiques, University of Cocody, Abidjan, Côte d’IvoireIntroduction: In recent years, intermittent preventive treatment for pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) has become policy in much of sub-Saharan Africa. But resistance to SP has been spreading across sub-Saharan Africa and thus the effectiveness of IPTp-SP has been questioned. The present study therefore sought to assess the incidence of placental malaria, low birth weight, and anemia of two IPTp-SP approaches (directly observed treatment scheme versus no directly observed treatment) in Anonkoua-Kouté and Samo, Côte d’Ivoire where the reported prevalence of dfr single mutant 108 was 62% and 52.2%, respectively.Methods: The study was a longitudinal design involving pregnant women and was conducted in Anonkoua-Kouté, a suburban area, and Samo, a rural area, from January 2008 through March 2009. Women of a pregnancy less than 28 weeks duration were randomized to receive SP (1.5 g/0.075 g SP) in a single intake twice and were followed up monthly until delivery. Doses were administered under supervision in the controlled IPTp group, while SP was given free to women in the uncontrolled IPTp group with a recommendation to take it at home. The primary end point was the proportion of low birth weight infants (body weight < 2500 g) and the secondary end point was the rate of severe anemia and placental malaria detected at delivery.Results: A total of 420 pregnant women were enrolled (212 and 208, respectively, in the controlled and uncontrolled groups). Delivery outcome was available for 378 women. In the modified intention-to-treat analysis, low birth weight infants were born from 15.5% of women of the uncontrolled IPTp group and from 11.9% of women in the controlled IPTp group (P = 0.31). The per-protocol population analysis showed consistent results. The proportion of women with placental malaria infection, moderate anemia (hemoglobin < 11 g/dL), and severe anemia (hemoglobin < 8 g/dL) at delivery were similar between the two groups (P > 0.05).Conclusion: The study showed that the two approaches were equivalent, suggesting that unsupervised IPTp-SP free of charge should be used in areas where implementation of the directly observed treatment scheme suffers from many constraints.Keywords: IPTp, SP efficacy, DOT scheme, resistance, Côte d’Ivoire&nbsp

The peer review process screens scientific articles for merit prior to acceptance or rejection for publication. After publication the process continues with scrutiny by other researchers as expressed in letters to the editor and other scientific research that either affirms or denies findings. Research into radiation effects directly affects the use of ionizing radiations in medicine. The quality of peer review of articles on radiation effects is therefore critical to the practice of medicine. This presentation will examine adequacy of peer review regarding recent articles on radiation effects that have appeared in the peer-reviewed literature. The purpose is to examine what factors in research techniques and analyses contribute to the quality and believability of the findings. Learning Objectives 1. To gain insight into the critical evaluation of scientific literature on bio effect s 2. To understand how to distinguish causation from correlation or association.

Analysing computations in neural circuits often uses simplified models because the actual neuronal implementation is not known. For example, a problem in vision, how the eye detects image motion, has long been analysed using Hassenstein-Reichardt (HR) detector or Barlow-Levick (BL) models. These both simulate motion detection well, but the exact neuronal circuits undertaking these tasks remain elusive. We reconstructed a comprehensive connectome of the circuits of Drosophila‘s motion-sensing T4 cells using a novel EM technique. We uncover complex T4 inputs and reveal that putative excitatory inputs cluster at T4’s dendrite shafts, while inhibitory inputs localize to the bases. Consistent with our previous study, we reveal that Mi1 and Tm3 cells provide most synaptic contacts onto T4. We are, however, unable to reproduce the spatial offset between these cells reported previously. Our comprehensive connectome reveals complex circuits that include candidate anatomical substrates for both HR and BL types of motion detectors.

Epidemiological research correlating cancer rates in a population of patients with radiation doses from medical X-rays is fraught with confounding factors that obfuscate the likelihood that any positive relationship is causal. This is a review of four studies involving some of those confounding factors. Comparisons of findings with other studies not encumbered by similar confounding factors can enhance assertions of causation between medical X-rays and cancer rates. Even so, such assertions rest significantly on opinions of researchers regarding the degree of consistency between findings among various studies. The question as to what degree any findings truly represent cause and effect will likely still meet with controversy. The importance of these findings to medicine should therefore not lie in any controversy regarding causation, but in what the findings potentially mean with regard to benefit and risk for patients and the professional practice of medicine.

Diagnostic radiology has an image problem. In its effort to develop a better understanding of benefit-risk in medical radiology, data on potential risks associated with medical imaging have been welcomed into the medical community. As such, risk perspectives and mantras from the occupational health profession have been adopted and applied to patients. These perspectives often focus on risk with only casual, incidental, or no reference to the benefits experienced by patients. These occupational health viewpoints have accumulated over decades, have overshadowed a very limited perspective about the benefits of medical X-rays, and have become an integrated part of our profession. This review argues that the medical profession should abandon perspectives on risk that are adopted from occupational health professions and focus on perspectives that realistically focus on the medical benefit-risk for patients.

The original conceptualization of usability was ease of use, this was later expanded into a multi-dimensional construct in ISO standards and usability literature. Such an expansion is seen as an improvement, since cross-study comparison or benchmarking cannot objectively be done without a common set of usability components being defined. The current issue lies in how these components are operationalized, measured and validated. Although ISO standards ties usability to contextual situations, recent research has started to also recognize psychographic and demographic variations within the same context. The purpose of this study is to review web site usability as it relates to ISO standards (more specifically ISO 9126, ISO 9241 and ISO/IEC 25010) and existing usability studies. Implications for researchers and practitioners are provided.

Recent results have shown the possibility of both reconstructing connectomes of small but biologically interesting circuits and extracting from these connectomes insights into their function. However, these reconstructions were heroic proof-of-concept experiments, requiring person-months of effort per neuron reconstructed, and will not scale to larger circuits, much less the brains of entire animals. In this paper we examine what will be required to generate and use substantially larger connectomes, finding five areas that need increased attention: firstly, imaging better suited to automatic reconstruction, with excellent z-resolution; secondly, automatic detection, validation, and measurement of synapses; thirdly, reconstruction methods that keep and use uncertainty metrics for every object, from initial images, through segmentation, reconstruction, and connectome queries; fourthly, processes that are fully incremental, so that the connectome may be used before it is fully complete; and finally, better tools for analysis of connectomes, once they are obtained.

Louis K Chang1, David Sarraf1,21Jules Stein Eye Institute, Department of Ophthalmology, University of California, Los Angeles, Los Angeles, CA, USA; 2Department of Ophthalmology, Greater LA VA Healthcare Center, Los Angeles, CAAbstract: Diabetic retinopathy (DR) is a major cause of blindness worldwide and is the number one cause of blindness in working-age individuals in developed countries. We review the current literature and discuss the pathogenesis, modifying risk factors, genetics, and treatment of DR. Special focus is placed on the rationale and effectiveness of therapeutic modalities, both current and future.