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Rationale and objectives Prostate MRI improves detection of clinically significant prostate cancer; however, its diagnostic performance has wide variation. Artificial intelligence (AI) has the potential to assist radiologists in the detection and classification of prostatic lesions. Herein, we aimed to develop and test a cascaded deep learning detection and classification system trained on biparametric prostate MRI using PI-RADS for assisting radiologists during prostate MRI read out. Materials and Methods T2-weighted, diffusion-weighted (ADC maps, high b value DWI) MRI scans obtained at 3 Tesla from two institutions (n = 1043 in-house and n = 347 Prostate-X, respectively) acquired between 2015 to 2019 were used for model training, validation, testing. All scans were retrospectively reevaluated by one radiologist. Suspicious lesions were contoured and assigned a PI-RADS category. A 3D U-Net-based deep neural network was used to train an algorithm for automated detection and segmentation of prostate MRI lesions. Two 3D residual neural network were used for a 4-class classification task to predict PI-RADS categories 2 to 5 and BPH. Training and validation used 89% (n = 1290 scans) of the data using 5 fold cross-validation, the remaining 11% (n = 150 scans) were used for independent testing. Algorithm performance at lesion level was assessed using sensitivities, positive predictive values (PPV), false discovery rates (FDR), classification accuracy, Dice similarity coefficient (DSC). Additional analysis was conducted to compare AI algorithm's lesion detection performance with targeted biopsy results. Results Median age was 66 years (IQR = 60-71), PSA 6.7 ng/ml (IQR = 4.7-9.9) from in-house cohort. In the independent test set, algorithm correctly detected 111 of 198 lesions leading to 56.1% (49.3%-62.6%) sensitivity. PPV was 62.7% (95% CI 54.7%-70.7%) with FDR of 37.3% (95% CI 29.3%-45.3%). Of 79 true positive lesions, 82.3% were tumor positive at targeted biopsy, whereas of 57 false negative lesions, 50.9% were benign at targeted biopsy. Median DSC for lesion segmentation was 0.359. Overall PI-RADS classification accuracy was 30.8% (95% CI 24.6%-37.8%). Conclusion Our cascaded U-Net, residual network architecture can detect, classify cancer suspicious lesions at prostate MRI with good detection, reasonable classification performance metrics.

Dyspnea is a common complaint in patients who present to the emergency department and can be due to numerous etiologies. This case report details a 90-year-old female with a history significant for hypertension, hyperlipidemia, and new diagnosis of ovarian malignancy whose symptoms increased over the past three days. Point-of-care Ultrasonography showed multiple B-lines, a plethoric IVC without respiratory variation, a markedly low EF and a lack of RV dilation. There was also no evidence of effusion which led the emergency medicine team to the diagnosis of acute decompensated heart failure. This quick diagnosis was possible due to using the standardized POCUS approach guided by the BEE FIRST algorithm. BEE FIRST can help physicians remember: B-lines are indicative of interstitial thickening, Effusion such as pericardial or pleural should be checked for, Ejection Fraction is useful in assessing for heart failure, IVC/Infection/Infarct correlates with central venous pressure, and can be used to assess volume status, check for enlargement, evidence of pneumonia, subpleural consolidation “shred sign”, hepatization of lung, and/or pulmonary infarction related to pulmonary embolism, Right Heart Strain can indicate pulmonary embolism or pulmonary hypertension, Sliding Lung can assess for pneumothorax and pleural characteristics, and lastly, Thrombosis/Tumor can assess for myxoma and interrogation of lower extremities for deep vein thrombosis can aid in dyspnea differentiation. In this report, we demonstrate how the framework BEE FIRST offers a standardized stepwise approach to the utilization of POCUS in a patient with acute dyspnea in the ED setting.

Emergency physicians often rely on heuristics to facilitate clinical decisions due to the large volume of patients they see daily. Consequently, they are vulnerable to error and bias. We report the case of a 69-year-old male that presented to the emergency department (ED) with shortness of breath, productive cough, and dyspnea on exertion. One day prior to ED admission, he was diagnosed with bronchitis; however, point-of-care ultrasound (POCUS) in the ED identified acute pulmonary embolism. This case illustrates the potential dangers of anchoring bias and shows the benefits of using point-of-care ultrasound of the lungs and heart to assist in the diagnosis of acute pulmonary embolism.

The fine structure of the IsoVector Giant Dipole Resonance (IVGDR) in the doubly-magic nuclei $^{40,48}$Ca observed in inelastic proton scattering experiments under $0^\circ$ is used to investigate the role of different mechanisms contributing to the IVGDR decay width. Characteristic energy scales are extracted from the fine structure by means of wavelet analysis. The experimental scales are compared to different theoretical approaches allowing for the inclusion of complex configurations beyond the mean-field level. Calculations are performed in the framework of RPA and beyond-RPA in a relativistic approach based on an effective meson-exchange interaction, with the UCOM effective interaction and, for the first time, with realistic two- plus three-nucleon interactions from chiral effective field theory employing the in-medium similarity renormalization group. All models highlight the role of Landau fragmentation for the damping of the IVGDR, while the differences in the coupling strength between one particle-one hole (1p-1h) and two particle-two hole (2p-2h) correlated (relativistic) and non-correlated (non-relativistic) configurations lead to very different pictures of the importance of the spreading width resulting in wavelet scales being a sensitive measure of their interplay. The relativistic approach with particle-vibration coupling, in particular, shows impressive agreement with the number and absolute values of the scales extracted from the experimental data., 10 pages, 4 figures

Palliative care is a field of medicine that delivers patient-centered care for individuals and their families suffering from serious illness at all stages of the disease trajectory. It addresses the major priorities of relieving suffering, establishing goals of care, and managing physical symptoms while integrating the psychosocial, cultural, spiritual, and existential complexities of coping with chronic illness. This article discusses the role of palliative care in the health care system. It reviews the importance of prognostication, disease trajectory, and communication. The role of the primary care physician as part of a multidisciplinary team member delivering primary palliative care is emphasized.

OBJECTIVE To determine the safety and efficacy of advanced practice provider (APP)-performed newborn circumcisions (NBCs), we reviewed outcomes of NBCs performed by pediatric urologists and APPs. We hypothesize comparable clinical outcomes between the groups. METHODS All urology performed NBCs during a 5-year period were reviewed, including time surrounding implementation of the APP-led clinic. Return to emergency department (ED) rates, return to operating room (OR) rates, and intraprocedure bleeding requiring intervention were reviewed. Fisher exact and Mann-Whitney testing were utilized. RESULTS There were no statistically significant differences in rates of intraprocedure bleeding, return to ED in 30days, return to OR for revision or other related penile surgery, or the overall number of patients with complications between the groups. Thirteen patients had complications in the APP cohort, compared to 8 in the urologist cohort. There was a difference in age and weight, with urologists performing NBCs on older and heavier patients. There was no difference in clinical outcomes between children over and under 10 pounds (4.5 kg). There was a significant difference in the need for revision circumcision when comparing children older vs younger than 30days (1.9% vs 0%, P = 0.034). CONCLUSION An APP-led NBC clinic is both safe and feasible. The widely used age and weight cutoffs for NBC need to be further evaluated, as there was no significant difference in clinical outcomes. This practice design provides pediatric urologists more time to focus on the most complex patients, both in the clinic and OR.

Background Patients with a prenatal diagnosis of lower urinary tract obstruction (LUTO) may undergo prenatal interventions, such as vesicoamniotic shunt (VAS) placement, as a temporary solution for relieving urinary tract obstruction. A recent FDA communication has raised awareness of the potential neurocognitive adverse effects of anesthesia in children. We hypothesized as to whether a prenatal LUTO staging system was predictive of the number of anesthesia events for prenatally diagnosed LUTO patients. Methods We retrospectively reviewed the prenatal and postnatal clinical records for patients with prenatally diagnosed LUTO from 2012 to 2015. Patients were stratified by prenatal VAS status and by LUTO disease severity according to Ruano et al. (Ultrasound Obstet Gynecol. 2016). Results 31 patients were identified with a prenatal LUTO diagnosis, and postnatal records were available for 21 patients (seven patients in each stage). When combining prenatal and postnatal anesthesia, there was a significant difference in the number of anesthesia encounters by stage (1.6, 3.7, and 6.7 for Stage I, II, and III respectively, p = .034). Upon univariate analysis, higher gestational age (GA) at birth was associated with a decreased number of anesthesia events in the first year (p = .031). Conclusions The majority of infants with prenatally diagnosed LUTO will undergo postnatal procedures with general anesthesia exposure in the first year of life. Patients with higher prenatal LUTO severity experienced a higher number of both prenatal and postnatal anesthesia encounters. In addition, higher GA at birth was associated with fewer anesthesia encounters in the first year. Level of evidence This is a prognostic study with Level IV evidence.

Objective To evaluate the management and clinical outcomes of nonfunctioning upper pole moieties treated with either upper pole heminephrectomy or upper pole preservation with lower ureteral reconstruction at a single tertiary institution. Methods After Institutional Review Board (IRB) approval, patients with duplicated systems undergoing upper pole heminephrectomy, ureteroureterostomy, or common sheath ureteral reimplantation from 2012-2017 were identified. Only patients with a nonfunctioning upper pole moiety on ultrasound or renal scan were included. Patients undergoing upper pole heminephrectomy were compared to those undergoing upper pole preservation with respect to demographics, anatomic variations preoperatively, and postoperative outcomes. Results Twenty-seven (57%) patients underwent upper pole preservation with lower ureteral reconstruction; 20 (43%) patients underwent upper pole heminephrectomy. Patients undergoing lower ureteral reconstruction were older (1.63 vs 2.76 years, P = .018) and more commonly presented with lower pole vesicoureteral reflux (67% vs 25%, P = .008). No significant difference in postoperative complications was seen between the two groups. After ureteroureterostomy, one patient developed new onset symptomatic reflux to the upper pole requiring intravesical reimplantation. In the heminephrectomy group, 4 of 11 patients with ureteroceles had ureterocelectomy with concomitant lower pole reimplantation. After heminephrectomy, two additional patients required further interventions: ureterocele excision and transurethral polyp excision. Conclusion For patients with nonfunctional upper poles, lower tract reconstruction is a safe alternative to upper pole heminephrectomy. No significant difference in outcomes was seen. Considering that nearly 1 of 3 of patients with upper pole heminephrectomy required additional lower urinary tract procedures, pursuing upper pole preservation with lower urinary tract reconstruction may be favorable.

Infrared (IR) optical materials have enabled a broad range of optical sensing and measurement applications in the mid-wave and long-wave IR. Many IR transmitting glasses are based on covalently-bonded selenides and tellurides, such as As2Se3 and GeTe2, which typically have relatively low glass transition temperatures (Tg) on the order of 200 to 350 °C. Many applications have working temperatures above the Tg of these materials, which compels the development of new IR materials. This work studies the underlying short-range order (SRO) structure and glass formability of a new family of ionically-bonded sulfide glasses, xBaS + yLa2S3 + (1 − x − y)GeS2, to develop high Tg optical materials with a broad IR transmission range. These sulfide glasses were produced by melting sulfide materials inside evacuated and sealed carbon-coated silica ampoules at 1150 °C for 12 h and quenching to room temperature to form glass. Glass samples were then characterized by IR and Raman spectroscopies and differential thermal analysis (DTA). It was found that by increasing the modifier concentration, the predominantly Ge4 SRO units, the superscript defines the number of bridging sulfur (BS) ions in the tetrahedral network found in GeS2 glasses, are ultimately converted to Ge0 units at >40 mol% network modifier content through the generation of non-bridging sulfur (NBS) ions. These molecular ionic units still form a glassy network, with some of the highest reported Tg values to date for a pure sulfide glass. This suggests that this composition has strong ionic bonds between negatively-charged tetrahedral SRO units and the positively-charged modifier cations. While the glass network is depolymerized in the high modifier content glasses though the formation of a high concentration of molecular ionic Ge0 SRO groups, they are, nevertheless, homogeneous glassy materials that exhibit the largest Tg and ΔT (difference between crystallization temperature, Tc, and Tg) values of glasses in this system, making them the optimal glasses for high Tg IR optical components, including, potentially, refractory IR optical fibers.

Loss-of-function mutations in progranulin (GRN) are a major genetic cause of frontotemporal dementia (FTD), possibly due to loss of progranulin’s neurotrophic and anti-inflammatory effects. Progranulin promotes neuronal growth and protects against excitotoxicity and other forms of injury. It is unclear if these neurotrophic effects are mediated through cellular signaling or through promotion of lysosomal function. Progranulin is a secreted proprotein that may activate neurotrophic signaling through cell-surface receptors. However, progranulin is efficiently trafficked to lysosomes and is necessary for maintaining lysosomal function. To determine which of these mechanisms mediates progranulin’s protection against excitotoxicity, we generated lentiviral vectors expressing progranulin (PGRN) or lysosome-targeted progranulin (L-PGRN). L-PGRN was generated by fusing the LAMP-1 transmembrane and cytosolic domains to the C-terminus of progranulin. L-PGRN exhibited no detectable secretion, but was delivered to lysosomes and processed into granulins. PGRN and L-PGRN protected against NMDA excitotoxicity in rat primary cortical neurons, but L-PGRN had more consistent protective effects than PGRN. L-PGRN’s protective effects were likely mediated through the autophagy-lysosomal pathway. In control neurons, an excitotoxic dose of NMDA stimulated autophagy, and inhibiting autophagy with 3-methyladenine reduced excitotoxic cell death. L-PGRN blunted the autophagic response to NMDA and occluded the protective effect of 3-methyladenine. This was not due to a general impairment of autophagy, as L-PGRN increased basal autophagy and did not alter autophagy after nutrient starvation. These data show that progranulin’s protection against excitotoxicity does not require extracellular progranulin, but is mediated through lysosomes, providing a mechanistic link between progranulin’s lysosomal and neurotrophic effects.

Conjoined twins are seen in approximately 1/500,000 live births, and therefore surgical management of urologic anomalies in conjoined twins has not been extensively reported. Various degrees of sharing of the urinary tracts and genitalia can be seen in different types of conjoined twins. Detailed preoperative imaging, including magnetic resonance imaging, computed tomography, and voiding cystourethrogram, is essential to define the anatomy and planning of a successful separation. We describe the urologic presentation, evaluation, and treatment of thoracoomphalopagus conjoined twins.

Thomas M. Franck's The Emerging Right to Democratic Governance has lived a dual existence. On the one hand, it is almost universally cited as having brought international lawyers into the freewheeling debate of the early 1990s among scholars of international relations, comparative politics, and political theory about the so-called “Third Wave” of democratization. On the other hand, the article is not infrequently described as a legal avatar of post-Cold War Western triumphalism, often sharing a sentence or a footnote with Francis Fukuyama's The End of History and the Last Man. From the standpoint of the two authors of this essay — one a long-time defender of Franck's thesis and the other a long-time critic — both of these broad-brush characterizations of the article contain elements of truth, but both are also woefully incomplete.

Coronary artery disease is a growing clinical problem in HIV-infected subjects. The increased risk of coronary events in this population has been linked to low levels of HDL, but the effects of HIV infection and anti-retroviral treatment (ART) on HDL structure and function remain unknown. Here, we aimed to determine the composition and function of HDL particles isolated from ART-naive and ART-positive HIV-infected patients.Proteomic profiling revealed decreased levels of paraoxonase (PON) 1 and PON 3 in HDL from HIV patients relative to HDL from uninfected controls (p0.0001), and PON activity of HDL from control group (0.13 ± 0.01 U/μl) was significantly higher than PON activity of HDL from HIV-infected untreated subjects (0.12 ± 0.01 U/μl, p = 0.0035), subjects treated with non-nucleoside reverse transcriptase inhibitor (NNRTI)-based therapy (0.11 ± 0.01 U/μl, p0.0001), subjects treated with protease inhibitor (PI)-based therapy with detectable viral load (0.11 ± 0.01 U/μl, p0.0001), and PI-treated patients with undetectable viral load (0.12 ± 0.01 U/μl, p = 0.0164). Lipidomic profiling uncovered a negative correlation between CD4 T cell counts and particle sphingomyelin, lyso-phosphatidylcholine and ether-linked phosphatidylserine content in the ART-naive (R(2) = 0.2611, p0.05; R(2) = 0.2722, p0.05; and R(2) = 0.3977, p0.05, respectively) but not treated HIV-infected subjects. Functional analysis demonstrated a negative correlation between cholesterol efflux capacity of HDL and viral load in the ART-naive HIV-infected group (R(2) = 0.26, p = 0.026).Taken together, these results indicate that HIV infection associates with a number of both protein and lipid compositional changes in HDL particles. Moreover, HIV infection affects cholesterol efflux function of HDL, thus contributing to an increased risk of atherosclerosis in this patient population.

For many processes with electroweak bosons in the final state, next-to-leading order QCD and, in some cases, electroweak corrections have been calculated for differential cross sections at hadron colliders. The calculational techniques and some phenomenological implications are reviewed in this contribution. Processes discussed include vector boson fusion and vector boson scattering, production of two and three electroweak bosons, potentially with jets, (VV j, VV jj and VVV events) and some Higgs production processes. All QCD corrections are implemented in the publicly available VBFNLO program package.

Objective To assess current diagnosis and management of adolescent varicoceles by pediatric urologists. Methods Online questionnaires assessing diagnosis and management approaches to pediatric and adolescent varicocele were distributed electronically to a national listing of pediatric urologists. Results Of 242 pediatric urologists surveyed, 131 (54%) responded to the survey. Only 3% of respondents operate on varicoceles at diagnosis, whereas 14% observe, and 83% base treatment on further indications. Varicocelectomy is most commonly performed for decreased ipsilateral testicular size (96%), testicular pain (79%), and altered semen analysis parameters (39%), with the mean age for varicocelectomy being 12.5 ± 3.1 years. Most physicians use ultrasonography (US) or Doppler US to aid in the diagnosis of varicoceles, and half of physicians would not repair incidental findings of varicocele on US. In an otherwise asymptomatic patient with a varicocele, 28% of physicians would consider varicocelectomy depending on varicocele grade. The most common surgical approaches to varicocelectomy were laparascopic (38%), subinguinal microsurgical (28%), inguinal (14%), and retroperitoneal (13%), and most physicians used loupes for these procedures. The most common complication experienced after adolescent varicocelectomy was hydrocele followed by hematoma, testicular atrophy, chronic pain, paresthesia, and varicocele recurrence or persistence. Only 58% of physicians had follow-up data on their varicocele patients, and 89% did not know whether patients developed infertility. Of patients who developed infertility, 39% had undergone varicocele repair. Conclusion Significant variation in diagnostic approaches, decision to treat, and operative approaches exists among pediatric urologists, and combined with a dearth of objective data, limits development of management guidelines.

This paper presents a new approach for precisely estimating the renal vascular dominant region using a Voronoi diagram. To provide computer-assisted diagnostics for the pre-surgical simulation of partial nephrectomy surgery, we must obtain information on the renal arteries and the renal vascular dominant regions. We propose a fully automatic segmentation method that combines a neural network and tensor-based graph-cut methods to precisely extract the kidney and renal arteries. First, we use a convolutional neural network to localize the kidney regions and extract tiny renal arteries with a tensor-based graph-cut method. Then we generate a Voronoi diagram to estimate the renal vascular dominant regions based on the segmented kidney and renal arteries. The accuracy of kidney segmentation in 27 cases with 8-fold cross validation reached a Dice score of 95%. The accuracy of renal artery segmentation in 8 cases obtained a centerline overlap ratio of 80%. Each partition region corresponds to a renal vascular dominant region. The final dominant-region estimation accuracy achieved a Dice coefficient of 80%. A clinical application showed the potential of our proposed estimation approach in a real clinical surgical environment. Further validation using large-scale database is our future work.

We performed a prospective study between January and November 2013 with inclusion of 84 consults encompassing 90 dermatologic conditions. This study received approval from the Philadelphia Field Initiating Group of Human Immunodeficiency Virus Trials, Philadelphia Department of Public Health, and University of Pennsylvania institutional review boards. Verbal informed consent and Health Insurance Portability and Accountability Act authorization were obtained from patients; written informed consent was obtained from providers. Consults were submitted to the University of Pennsylvania by 25 primary care providers at the Jonathan Lax Center, the Dr. Bernett L. Johnson, Jr. Sayre Health Center, and eight Philadelphia Department of Public Health centers using the AccessDerm (Vignet Corporation, Fairfax, VA) mobile platform.4 Diagnoses and management plans, initially drafted by dermatology residents, were reviewed, edited, and submitted by attending dermatologists. Nine residents and nine attending dermatologists responded to consults. For each dermatologic condition, two investigators (CAN, JT) independently determined the concordance of differential diagnoses and management plans between resident and attending dermatologists. Cohen’s κ assessing inter-rater reliability (95% confidence interval) for diagnostic and management concordance between the two investigators were 0.94 (0.91–0.98) and 0.87 (0.78–0.90), respectively. Statistical analyses were performed in Stata 12.1 (StatCorp LP, College Station, TX). Each resident responded to a median (interquartile range) of 9 (4–15) consults. The number of responses stratified by dermatology training year was: 10 (12%) first, 29 (34%) second, and 45 (54%) third year residents. Based on the leading diagnosis of the attending dermatologist or definitive diagnosis when available, dermatologic conditions were classified into the following categories: 24 (27%) eczematous conditions, 13 (14%) infectious diseases, 7 (8%) benign tumors or proliferations, 6 (7%) papulosquamous conditions, 5 (6%) pigmented disorders, 4 (4%) acneiform or follicular occlusion disorders, 4 (4%) premalignant or malignant lesions, 23 (26%) other, and 4 (4%) indeterminate. Diagnoses and management plans between resident and attending dermatologists were fully concordant for 53% and 65% of dermatologic conditions, respectively (Figure 1). Table I categorizes the changes made by attending dermatologists for those conditions with at least partial management discordance (adapted from Lamel et al5). Most changes were consistent with recommendation for education or observation (53%) and medication initiation or discontinuation (50%). Recommendation for in-person evaluation was concordant in 93% of consults. Figure 1 Diagnostic and management concordance between resident and attending dermatologists. Table I Categories of change in management With the development of sustainable teledermatology programs, it is important for dermatologists to become familiar with the strengths and limitations of this practice model. Our data revealed at least partial diagnostic and management discordance between resident and attending dermatologists for 47% and 35% of dermatologic conditions, respectively. Although limited by small sample size, this study suggests that teledermatology provides residents an opportunity for practice-based learning. Further research is required to evaluate educational outcome measures.

The availability of nitrogen (N) to plants has a profound impact on carbohydrate and protein metabolism, but little is known about its effect on membrane lipid species. This study examines the changes in galactolipid and phospholipid species in soybean as affected by the availability of N, either supplied to soil or obtained through Bradyrhizobium japonicum nodulation. When N was limited in soil, the content of galactolipids, monogalactosyldiacylglycerol (MGDG) and digalactosyldiacyglycerol (DGDG), decreased drastically in leaves, while a smaller decrease of DGDG was observed in roots. In both leaves and roots, the overall content of different phospholipid classes was largely unchanged by N limitation, although some individual phospholipid molecular species did display significant changes. Nodulation with Bradyrhizobium of soybean grown in N-deficient soil resulted in a large increase in levels of plastidic lipid classes, MGDG, DGDG, and phosphatidylglycerol, along with smaller increases in non-plastidic phospholipids in leaves. Nodulation also led to higher levels of phospholipids in roots without changes in root levels of MGDG and DGDG. Overall, N availability alters lipid content more in leaves than roots and more in galactolipids than phospholipids. Increased N availability leads to increased galactolipid accumulation in leaves, regardless of whether N is supplied from the soil or symbiotic fixation.

Graphical abstract, Highlights • Novel haustral fold matching algorithm. • Achieves 96.1% mean accuracy over 1743 reference points in 17 CTC datasets. • New initialisation to non-rigid intensity-based surface registration method. • Full method shows 6.0 mm mean error. • Use of initialisation shows significant improvement (p, Computed Tomographic (CT) colonography is a technique used for the detection of bowel cancer or potentially precancerous polyps. The procedure is performed routinely with the patient both prone and supine to differentiate fixed colonic pathology from mobile faecal residue. Matching corresponding locations is difficult and time consuming for radiologists due to colonic deformations that occur during patient repositioning. We propose a novel method to establish correspondence between the two acquisitions automatically. The problem is first simplified by detecting haustral folds using a graph cut method applied to a curvature-based metric applied to a surface mesh generated from segmentation of the colonic lumen. A virtual camera is used to create a set of images that provide a metric for matching pairs of folds between the prone and supine acquisitions. Image patches are generated at the fold positions using depth map renderings of the endoluminal surface and optimised by performing a virtual camera registration over a restricted set of degrees of freedom. The intensity difference between image pairs, along with additional neighbourhood information to enforce geometric constraints over a 2D parameterisation of the 3D space, are used as unary and pair-wise costs respectively, and included in a Markov Random Field (MRF) model to estimate the maximum a posteriori fold labelling assignment. The method achieved fold matching accuracy of 96.0% and 96.1% in patient cases with and without local colonic collapse. Moreover, it improved upon an existing surface-based registration algorithm by providing an initialisation. The set of landmark correspondences is used to non-rigidly transform a 2D source image derived from a conformal mapping process on the 3D endoluminal surface mesh. This achieves full surface correspondence between prone and supine views and can be further refined with an intensity based registration showing a statistically significant improvement (p

Dietary omega-3 fatty acids (n-3 PUFA), notably eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), impart health benefits in humans and animals. In horses, dietary n-3 PUFAs elevate EPA and DHA and may promote anti-inflammatory effects. No reports document effects of dietary n-3 PUFA on fatty acyl components of circulating and cellular phospholipids in horses nor whether responses to dietary n-3 PUFA are similar among horse breeds. Ten Quarter Horse and 10 American Miniature Horse mares were assigned to n-3 PUFA (64.4 mg· kg body weight [BW] −1 ·d −1 ) or control diet for 56 days. Blood was sampled at 0, 28, and 56 days. Apparent phospholipid molecular species from several classes (phosphatidylcholine [PC]; "ether-linked" phosphatidylcholine [i.e., alk(en)yl, acyl glycerophosphocholine] [ePC]; phosphatidylethanolamine [PE]; phosphatidylinositol [PI]; and phosphatidylserine [PS]) were determined in plasma and peripheral blood mononuclear cells (PBMC) by mass spectrometry. Statistical analysis showed that six phospholipid species had diet × day interactions ( P P

Decades after the advent of assisted reproductive technology (ART) that allows prospective parents to deselect embryos with grave genetic illnesses – a procedure called preimplantation genetic diagnosis (PGD) – it remains a tool largely of upper class whites. In the wake of the Supreme Court’s decision in Whole Woman’s Health v. Hellerstedt, I argue that the time has come to focus on access in this area of reproductive rights. The next logical step is to rebut the presumption that reproductive liberty is only a negative right that prevents government interference with decisions about whether and how to procreate or not to procreate. If liberty is tied to equality through access to medical procedures, scholars must finally answer the question of what equality requires in a system that permits the use of ARTs and frame reproductive liberty as a positive right. This Article shows how the current system of assisted reproduction already distinguishes between the “in” group and the “out” group. I use PGD here as a lens to focus on ARTs more generally. Section I explores the literature’s focus on the use and growth of PGD for genetic selection unrelated to the prevention of genetic disease (nontherapeutic PGD), including the use of PGD for sex and other physical trait selection. The scholarly overemphasis on the tricky moral quandaries associated with the nontherapeutic use of PGD where liberty concerns are at the forefront impedes any proposed solutions to unequal access to using PGD to prevent inherited illnesses. Section II explores how existing jurisprudence ignores the role of income inequality and broader social concerns in deciding disputes related to PGD. Finally, I discuss in Section III how the combined effect of the Affordable Care Act (ACA) antidiscrimination and essential health benefit mandates is to focus on ensuring equality of access to healthcare, particularly for underserved populations. Reproductive technology should be included among the essential health benefits the ACA requires, and the illustration of therapeutic PGD demonstrates why. The new eugenics privileges wealthy whites above other races and classes, and exacerbates race and class distinctions.

The patatin-related phospholipase A (pPLA) hydrolyzes membrane glycerolipids to produce monoacyl compounds and free fatty acids. Phospholipids are cleaved by pPLAIIα at the sn-1 and sn-2 positions, and galactolipids, including those containing oxophytodienoic acids, can also serve as substrates. Ablation of pPLAIIα decreased lysophosphatidylcholine and lysophosphatidylethanolamine levels, but increased free linolenic acid. pPLAIIα-deficient plants displayed a higher level of jasmonic acid and methyl jasmonate, as well as the oxylipin-biosynthetic intermediates 13-hydroperoxylinolenic acid and 12-oxophytodienoic acid than wild-type (WT) plants. The expression of genes involved in oxylipin production was also higher in the pPLAIIα-deficient mutant than in WT plants. The mutant plants lost water more quickly than WT plants. The stomata of WT and mutant plants responded similarly to abscisic acid. In response to desiccation, the mutant and WT leaves produced abscisic acid at the same rate, but, after 4 h of desiccation, the jasmonic acid level was much higher in mutant than WT leaves. These results indicate that pPLAIIα negatively regulates oxylipin production and suggest a role in the removal of oxidatively modified fatty acids from membranes.

Objectives Endoscopic injection of non–animal-stabilized hyaluronic acid/dextranomer gel is an increasingly recognized treatment option for vesicoureteral reflux. The procedure is minor compared with open surgery and, when successful, avoids the need for long-term antibiotic prophylaxis. We present data from 3 years of using non–animal-stabilized hyaluronic acid/dextranomer gel to treat children with vesicoureteral reflux. Methods Pediatric patients aged 16 years with uncomplicated primary vesicoureteral reflux were recruited for endoscopic treatment with non–animal-stabilized hyaluronic acid/dextranomer gel. A follow-up voiding cystourethrogram was scheduled at 2 weeks after treatment, and vesicoureteral reflux resolution was defined as grade 0. Repeat non–animal-stabilized hyaluronic acid/dextranomer gel treatment was offered to patients with persistent vesicoureteral reflux. Results Of 178 patients treated, 12 were lost to follow-up or yet to undergo post-treatment voiding cystourethrogram. The 166 remaining patients (efficacy population) had a mean age of 4.21 years (range: 0-16), and the median reflux grade was 3 (range: 1-5). Vesicoureteral reflux was resolved in 81.9% of patients and 86.4% of ureters after initial endoscopic treatment with non–animal-stabilized hyaluronic acid/dextranomer gel. The overall reflux resolution rate for patients increased to 89.6% after a second treatment in 19 patients, and 90.2% after a third treatment in 1 patient. No adverse events were reported. Five patients underwent open ureteral reimplantation after failed endoscopic injections. Conclusions Endoscopic treatment with non–animal-stabilized hyaluronic acid/dextranomer gel is effective in a high proportion of children with vesicoureteral reflux and, in our opinion, should be considered as a first-line treatment option.

To determine the prevalence of urologic disease among infants hospitalized for urinary tract infections (UTIs) at our institution. The prevalence of urologic anomalies among infants (400 days old) hospitalized for UTIs has not been previously reported.We retrospectively examined the records of all infants hospitalized for UTI at our institution, a free-standing children's hospital in the United States, for a 10-year period. Race, sex, and subsequent urologic diagnosis (using codes from the 9(th) edition of the International Classification of Diseases [ICD-9] were tabulated. Individual charts were reviewed to confirm documentation and workup of UTI.We identified 914 infants hospitalized at our institution from January 1996 to December 2007, with an ICD-9-coded diagnosis of UTI. Of these 914 infants, 258 were subsequently given a urologic diagnosis. However, only 130 of these patients had well-documented UTI (14.2% of 914 children). Of this cohort, 55.4% were boys. The most common diagnoses were hydronephrosis (37.7%), vesicoureteral reflux (69.2%), and obstructive uropathy (23.1%).Our data have indicated thator =14% of all infants hospitalized for UTI have urologic anomalies. Vesicoureteral reflux, obstructive uropathy, and hydronephrosis are common diagnoses. We therefore conclude that infants admitted with a diagnosis of UTI should undergo screening for anatomic abnormalities.

Objectives To use decision analysis to determine the economic benefits of early vs late orchiopexy, specifically with respect to testicular cancer development and management. Studies have suggested that prepubertal orchiopexy might confer additional protection from the development of testicular cancer compared with postpubertal orchiopexy. Infant surgery is often performed by pediatric subspecialists and hence might be more costly. Although rare, testicular cancer can require significant medical expenditures. Methods We examined the resource index (RI) (physician charges and hospital costs) from the medical establishment's perspective. Economic modeling was performed to determine whether early or late orchiopexy minimized the RI. The stage- and histologic-specific costs of subsequent testicular cancer were incorporated into our models. The variables were tested over realistic ranges in the sensitivity analysis to determine the threshold values. Results In the base case analysis, the RI for infant and postpubertal orchiopexy was $7500 and $10 928 per patient, respectively. The sensitivity analysis demonstrated that the costs for operating room time, physicians' fees, operative times, and baseline cancer risk were important parameters. However, only the surgeons' fees demonstrated threshold values. The RI for treating cancer and the cancer risk reduction after early orchiopexy did not significantly affect our models. Conclusions Our models of orchiopexy for prevention of testicular cancer showed that infant orchiopexy is less costly than later surgery, provided that the surgeons' fees are not excessive. It appears that early surgery might significantly reduce the treatment costs of testicular cancer for cryptorchid boys and supports the current standard of care in the United States.

The CINS (Combined Ion and Neutron Spectrometer) consists of three detector systems: a boron-loaded plastic scintillator for medium energy neutrons, a silicon detector system for high-energy neutrons, and a charged particle stack containing both silicon detectors and scintillators. A readout system built for the charged particle stack is described here. The stack must be able to detect particles over a wide range of charge and energy. It contains 7 detectors, including 4 silicon detectors that each have two output paths. The readout must have a large usable dynamic range and must be able to handle the relatively high event rates that occur when the stack is placed in an accelerator beam. The data acquisition system detects events (that is, compares incoming signals to user-supplied trigger definitions), proceeds to capture waveform data from the preamplifiers, and saves the data to a hard drive. Although only used with the charged particle stack to date, the system can also be used with the other elements of CINS.

The Combined Ion and Neutron Spectrometer, CINS, is designed to measure the charged and neutral particles that contribute to the radiation dose and dose equivalent received by humans in spaceflight. As the depth of shielding increases, either onboard a spacecraft or in a surface habitat, the relative contribution of neutrons increases significantly, so that obtaining accurate neutron spectra becomes a critical part of any dosimetric measurements. The spectrometer system consists of high- and medium-energy neutron detectors along with a charged-particle detector telescope based on a standard silicon stack concept. The present version of the design is intended for ground-based use at particle accelerators; future iterations of the design can easily be streamlined to reduce volume, mass, and power consumption to create an instrument package suitable for spaceflight. The detector components have been tested separately using high-energy heavy ion beams at the NASA Space Radiation Laboratory at the Brookhaven National Laboratory and neutron beams at the Radiological Research Accelerator Facility operated by Columbia University. Here, we review the progress made in fabricating the hardware, report the results of several test runs, and discuss the remaining steps necessary to combine the separate components into an integrated system. A custom data acquisition system built for CINS is described in an accompanying article.

Can fiduciaries be made to serve public goals? The movement under the Patient Protection and Affordable Care Act (“ACA”) towards universal access to health insurance requires us to focus on the fiduciary relationships between large organizations providing access to healthcare and the populations they serve. These relationships have become a collective undertaking instead of a direct, personal relationship. In this Article, I introduce the concept of the collective fiduciary in response to the shift towards uniform, national goals in the realm of health insurance and healthcare. Only through a collective approach can we hold fiduciaries accountable for the welfare of many instead of one or a few individuals. While other scholars have focused on the individual whose fortunes or health are controlled by a fiduciary, this has made it difficult to collect information about fiduciary actions and obtain consistent and coherent decisions from fiduciaries. My argument here is that this is not a problem that can be fixed at the level of the individual fiduciary or individual beneficiary. I examine the expansion of the role of the fiduciary as a result of growing demand for private welfare benefits in the United States. My concern here is with the expansion of health insurance and the administration of health benefits. If patients are denied benefits, then they are effectively denied access to service providers. In a space where the government has been, until now, largely absent both by choice and because of a lack of agreement on policy direction, individual decisions by fiduciaries add up to the only large scale policy existing for private benefits. Fiduciaries can and will undo the goal of expanding access to healthcare under the ACA unless ERISA’s fiduciary regime (the example I focus on in this Article) is altered. Though I explore several possible solutions, I ultimately argue that fiduciary duties are only meaningful when denials of benefit claims are supervised and capped by government actors.

Lipid profiling is a targeted metabolomics platform that provides a comprehensive analysis of lipid species with high sensitivity. Profiling based on electrospray ionization tandem mass spectrometry (ESI-MS/MS) provides quantitative data and is adaptable to high throughput analyses. Here we report the profiling of 140 apparent molecular species of polar glycerolipids in Arabidopsis leaves, flower stalks, flowers, siliques, roots, and seeds. Considerable differences in lipid species occur among these organs, providing insights into the different lipid metabolic activities in a specific organ. In addition, comparative profiling between wild-type and a knockout mutant pldalpha1 (locus ID: AT3G15730) provides insight into the metabolic function of phospholipase D (PLD) in different organs. PLDalpha1 contributes significantly to phosphatidic acid (PA) levels in roots, seeds, flowers, and flower stalks, but little to basal PA levels in siliques and leaves. In seeds of the pldalpha1 mutant plants, levels of PA, lysophosphatidylcholine, and lysophosphatidylethanolamine were significantly lower than those of wild-type seeds, suggesting a role for PLDalpha1 in membrane lipid degradation in seeds.

Resume Cet article, qui traite de la difficile prise en charge de la souffrance psychique dans les instituts religieux, s’inscrit dans une reflexion plus large sur les violences corporelles et symboliques dans la vie consacree catholique 1 . Mon champ d’analyse anthropologique repose sur une investigation a long terme (1997-2003), ou l’observation participante, de nombreux entretiens qualitatifs et des temoignages epistolaires me permettent, dans un monde aussi soucieux de discretion, d’apprehender, non seulement les affects mobilises ou refoules mais, egalement, la souffrance chronique. Cette demarche emprunte a l’hermeneutique son champ d’analyse, ou l’exploitation des entretiens s’articule sur de rares ouvrages medicaux psychiatriques, des autobiographies d’anciens ministres des cultes 2 et des textes normatifs de l’Eglise, afin de presenter ce « mal etre » non pas comme un phenomene marginal, mais pouvant affecter un grand nombre d’individus 3 .

The behavior of a particular bacterial genetic system has been interpreted as evidence that selective stress induces general mutagenesis or even preferentially directs mutations to sites that improve growth (adaptive mutation). It has been proposed that changes in mutability are a programmed response to stress in non-growing cells. In contrast, the amplification-mutagenesis model suggests that stress has no direct effect on the mutation rate and that mutations arise in cells growing under strong selection. In this model, stress serves only as a selective pressure that favors cells with multiple copies of a growth-limiting gene. Mutations are made more probable because more target copies are added to the selection plate-more cells with more mutational targets per cell. The amplification-mutagenesis process involves standard genetic events and therefore should apply to all biological systems. Idiosyncrasies of the particular system described here accelerate this process, allowing an evolutionary series of events to be completed in only a few days.

The extracellular AVR4 elicitor of the pathogenic fungus Cladosporium fulvum induces defense responses in the tomato genotype Cf-4. Here, the four disulfide bonds of AVR4 were identified as Cys-11-41, Cys-21-27, Cys-35-80, and Cys-57-72 by partial reduction with Tris-(2-carboxyethyl)-phosphine hydrochloride, subsequent cyanylation, and base-catalyzed chain cleavage. The resulting peptide fragments were analyzed by mass spectrometry. Sequence homology and the disulfide bond pattern revealed that AVR4 contains an invertebrate (inv) chitin-binding domain (ChBD). Binding of AVR4 to chitin was confirmed experimentally. The three disulfide bonds encompassing the inv ChBD motif are also required for protein stability of AVR4. Independent disruption of each of the three conserved disulfide bonds in AVR4 resulted in a protease-sensitive protein, whereas the fourth disulfide bond appeared not to be required for protein stability. Most strains of C. fulvum virulent on Cf-4 tomato contain Cys to Tyr substitutions in AVR4 involving two (Cys-11-41, Cys-35-80) of the three disulfide bonds present in the inv ChBD motif. These natural Cys to Tyr mutant AVR4 proteins did retain their chitin binding ability and when bound to chitin were less sensitive to proteases. Thus, the widely applied tomato Cf-4 resistance gene is circumvented by C. fulvum by amino acid substitutions affecting two disulfide bonds in AVR4 resulting in the absence of the corresponding AVR4 isoforms in apoplastic fluid. However, these natural isoforms of AVR4 appear to have retained their intrinsic function, i.e. binding to chitin present in the cell wall of C. fulvum, most likely to protect it against the deleterious effects of plant chitinases.