Long-Term Follow-Up After Non-operative Management of Blunt Splenic and Liver Injuries: A Questionnaire-Based Survey.

BACKGROUND Non-operative management (NOM) of blunt splenic or liver injuries (solid organ injury, SOI) has become the standard of care in hemodynamically stable patients. However, the incidence of long-term symptoms in these patients is currently not known. The aim of this study was to assess long-term symptoms in patients undergoing successful NOM (sNOM) for SOI. METHODS Long-term posttraumatic outcomes including chronic abdominal pain, irregular bowel movements, and recurrent infections were assessed using a specifically designed questionnaire and analyzed by univariable analysis. RESULTS Eighty out of 138 (58%) patients with SOI undergoing sNOM) responded to the questionnaire. Median (IQR) follow-up time was 48.8 (28) months. Twenty-seven (34%) patients complained of at least one of the following symptoms: 17 (53%) chronic abdominal pain, 13 (41%) irregular bowel movements, and 8 (25%) recurrent infections. One female patient reported secondary infertility. No significant association between the above-mentioned symptoms and the Injury Severity Score, amount of hemoperitoneum, or high-grade SOI was found. Patients with chronic pain were significantly younger than asymptomatic patients (32.1 ± 14.5 vs. 48.3 ± 19.4 years, p = 0.002). Irregular bowel movements were significantly more frequent in patients with severe pelvic fractures (15.4 vs. 0.0%, p = 0.025). A trend toward a higher frequency of recurrent infections was found in patients with splenic injuries (15.9 vs. 2.8%, p = 0.067). CONCLUSION A third of patients with blunt SOI undergoing sNOM reported long-term abdominal symptoms. Younger age was associated with chronic abdominal symptoms. More studies are warranted to investigate long-term outcomes immunologic sequelae in patients after sNOM for SOI

Cushing Syndrome in a 6-Month-Old Infant due to Adrenocortical Tumor

Cushing syndrome is rare in infancy and usually due to an adrenocortical tumor (ACT). We report an infant with Cushing syndrome due to adrenocortical carcinoma. The patient presented at six months of age with a three-month history of growth failure, rapid weight gain, acne, and irritability. Physical examination showed obesity, hypertension, and Cushingoid features. Biochemical evaluation showed very high serum cortisol, mildly elevated testosterone, and suppressed ACTH. Abdominal MRI revealed a heterogeneous right adrenal mass extending into the inferior vena cava. Evaluation for metastases was negative. The tumor was removed surgically en bloc. Pathologic examination demonstrated low mitotic rate, but capsular and vascular invasion. She received no adjuvant therapy. Her linear growth has improved and Cushingoid features resolved. Hormonal markers and quarterly PET scans have been negative for recurrence 24 months postoperatively. In conclusion, adrenocortical neoplasms in children are rare, but should be considered in the differential diagnosis of Cushing syndrome

New England Wind Energy Education Project (NEWEEP)

Project objective is to develop and disseminate accurate, objective information on critical wind energy issues impacting market acceptance of hundreds of land-based projects and vast off-shore wind developments proposed in the 6-state New England region, thereby accelerating the pace of wind installation from today's 140 MW towards the region's 20% by 2030 goals of 12,500 MW. Methodology: This objective will be accomplished by accumulating, developing, assembling timely, accurate, objective and detailed information representing the 'state of the knowledge' on critical wind energy issues impacting market acceptance, and widely disseminating such information. The target audience includes state agencies and local governments; utilities and grid operators; wind developers; agricultural and environmental groups and other NGOs; research organizations; host communities and the general public, particularly those in communities with planned or operating wind projects. Information will be disseminated through: (a) a series of topic-specific web conference briefings; (b) a one-day NEWEEP conference, back-to-back with a Utility Wind Interest Group one-day regional conference organized for this project; (c) posting briefing and conference materials on the New England Wind Forum (NEWF) web site and featuring the content on NEWF electronic newsletters distributed to an opt-in list of currently over 5000 individuals; (d) through interaction with and participation in Wind Powering America (WPA) state Wind Working Group meetings and WPA's annual All-States Summit, and (e) through the networks of project collaborators. Sustainable Energy Advantage, LLC (lead) and the National Renewable Energy Laboratory will staff the project, directed by an independent Steering Committee composed of a collaborative regional and national network of organizations. Major Participants - the Steering Committee: In addition to the applicants, the initial collaborators committing to form a Steering Committee consists of the Massachusetts Renewable Energy Trust; Maine Public Utilities Commission; New Hampshire office of Energy & Planning, the Connecticut Clean Energy Fund;, ISO New England; Utility Wind Interest Group; University of Massachusetts Wind Energy Center; Renewable Energy New England (a new partnership between the renewable energy industry and environmental public interest groups), and Lawrence Berkeley National Laboratory (conditionally). The Steering Committee will: (1) identify and prioritize topics of greatest interest or concern where detailed, objective and accurate information will advance the dialogue in the region; (2) identify critical outreach venues, influencers and experts; (3) direct and coordinate project staff; (4) assist project staff in planning briefings and conferences described below; (5) identify topics needing additional research or technical assistance and (6) identify and recruit additional steering committee members. Impacts/Benefits/Outcomes: By cutting through the clutter of competing and conflicting information on critical issues, this project is intended to encourage the market's acceptance of appropriately-sited wind energy generation

Three-Dimensional Ultrasound Guidance of Autonomous Robotic Breast Biopsy: Feasibility Study

Feasibility studies of autonomous robot biopsies in tissue have been conducted using real time 3D ultrasound combined with simple thresholding algorithms. The robot first autonomously processed 3D image volumes received from the ultrasound scanner to locate a metal rod target embedded in turkey breast tissue simulating a calcification, and in a separate experiment, the center of a water-filled void in the breast tissue simulating a cyst. In both experiments the robot then directed a needle to the desired target, with no user input required. Separate needle-touch experiments performed by the image-guided robot in a water tank yielded an rms error of 1.15 mm

Biased Signaling of CCL21 and CCL19 Does Not Rely on N-Terminal Differences, but Markedly on the Chemokine Core Domains and Extracellular Loop 2 of CCR7

Chemokine receptors play important roles in the immune system and are linked to several human diseases. Targeting chemokine receptors have so far shown very little success owing to, to some extent, the promiscuity of the immune system and the high degree of biased signaling within it. CCR7 and its two endogenous ligands display biased signaling and here we investigate the differences between the two ligands, CCL21 and CCL19, with respect to their biased activation of CCR7. We use bystander bioluminescence resonance energy transfer (BRET) based signaling assays and Transwell migration assays to determine (A) how swapping of domains between the two ligands affect their signaling patterns and (B) how receptor mutagenesis impacts signaling. Using chimeric ligands we find that the chemokine core domains are central for determining signaling outcome as the lack of β-arrestin-2 recruitment displayed by CCL21 is linked to its core domain and not N-terminus. Through a mutagenesis screen, we identify the extracellular domains of CCR7 to be important for both ligands and show that the two chemokines interact differentially with extracellular loop 2 (ECL-2). By using in silico modeling, we propose a link between ECL-2 interaction and CCR7 signal transduction. Our mutagenesis study also suggests a lysine in the top of TM3, K1303.26, to be important for G protein signaling, but not β-arrestin-2 recruitment. Taken together, the bias in CCR7 between CCL19 and CCL21 relies on the chemokine core domains, where interactions with ECL-2 seem particularly important. Moreover, TM3 selectively regulates G protein signaling as found for other chemokine receptors.publishe

Infants with esophageal atresia and right aortic arch: Characteristics and outcomes from the Midwest Pediatric Surgery Consortium

Purpose Right sided aortic arch (RAA) is a rare anatomic finding in infants with esophageal atresia with or without tracheoesophageal fistula (EA/TEF). In the presence of RAA, significant controversy exists regarding optimal side for thoracotomy in repair of the EA/TEF. The purpose of this study was to characterize the incidence, demographics, surgical approach, and outcomes of patients with RAA and EA/TEF. Methods A multi-institutional, IRB approved, retrospective cohort study of infants with EA/TEF treated at 11 children's hospitals in the United States over a 5-year period (2009 to 2014) was performed. All patients had a minimum of one-year follow-up. Results In a cohort of 396 infants with esophageal atresia, 20 (5%) had RAA, with 18 having EA with a distal TEF and 2 with pure EA. Compared to infants with left sided arch (LAA), RAA infants had a lower median birth weight, (1.96 kg (IQR 1.54–2.65) vs. 2.57 kg (2.00–3.03), p = 0.01), earlier gestational age (34.5 weeks (IQR 32–37) vs. 37 weeks (35–39), p = 0.01), and a higher incidence of congenital heart disease (90% vs. 32%, p  0.29). Conclusion RAA in infants with EA/TEF is rare with an incidence of 5%. Compared to infants with EA/TEF and LAA, infants with EA/TEF and RAA are more severely ill with lower birth weight and higher rates of prematurity and complex congenital heart disease. In neonates with RAA, surgical repair of the EA/TEF is technically feasible via thoracotomy from either chest. A higher incidence of anastomotic strictures may occur with a right-sided approach

Draft Genome Sequencing of Giardia intestinalis Assemblage B Isolate GS: Is Human Giardiasis Caused by Two Different Species?

Giardia intestinalis is a major cause of diarrheal disease worldwide and two major Giardia genotypes, assemblages A and B, infect humans. The genome of assemblage A parasite WB was recently sequenced, and the structurally compact 11.7 Mbp genome contains simplified basic cellular machineries and metabolism. We here performed 454 sequencing to 16× coverage of the assemblage B isolate GS, the only Giardia isolate successfully used to experimentally infect animals and humans. The two genomes show 77% nucleotide and 78% amino-acid identity in protein coding regions. Comparative analysis identified 28 unique GS and 3 unique WB protein coding genes, and the variable surface protein (VSP) repertoires of the two isolates are completely different. The promoters of several enzymes involved in the synthesis of the cyst-wall lack binding sites for encystation-specific transcription factors in GS. Several synteny-breaks were detected and verified. The tetraploid GS genome shows higher levels of overall allelic sequence polymorphism (0.5 versus <0.01% in WB). The genomic differences between WB and GS may explain some of the observed biological and clinical differences between the two isolates, and it suggests that assemblage A and B Giardia can be two different species

Ultra-rare genetic variation in common epilepsies: a case-control sequencing study

BACKGROUND:Despite progress in understanding the genetics of rare epilepsies, the more common epilepsies have proven less amenable to traditional gene-discovery analyses. We aimed to assess the contribution of ultra-rare genetic variation to common epilepsies. METHODS:We did a case-control sequencing study with exome sequence data from unrelated individuals clinically evaluated for one of the two most common epilepsy syndromes: familial genetic generalised epilepsy, or familial or sporadic non-acquired focal epilepsy. Individuals of any age were recruited between Nov 26, 2007, and Aug 2, 2013, through the multicentre Epilepsy Phenome/Genome Project and Epi4K collaborations, and samples were sequenced at the Institute for Genomic Medicine (New York, USA) between Feb 6, 2013, and Aug 18, 2015. To identify epilepsy risk signals, we tested all protein-coding genes for an excess of ultra-rare genetic variation among the cases, compared with control samples with no known epilepsy or epilepsy comorbidity sequenced through unrelated studies. FINDINGS:We separately compared the sequence data from 640 individuals with familial genetic generalised epilepsy and 525 individuals with familial non-acquired focal epilepsy to the same group of 3877 controls, and found significantly higher rates of ultra-rare deleterious variation in genes established as causative for dominant epilepsy disorders (familial genetic generalised epilepsy: odd ratio [OR] 2·3, 95% CI 1·7-3·2, p=9·1 × 10-8; familial non-acquired focal epilepsy 3·6, 2·7-4·9, p=1·1 × 10-17). Comparison of an additional cohort of 662 individuals with sporadic non-acquired focal epilepsy to controls did not identify study-wide significant signals. For the individuals with familial non-acquired focal epilepsy, we found that five known epilepsy genes ranked as the top five genes enriched for ultra-rare deleterious variation. After accounting for the control carrier rate, we estimate that these five genes contribute to the risk of epilepsy in approximately 8% of individuals with familial non-acquired focal epilepsy. Our analyses showed that no individual gene was significantly associated with familial genetic generalised epilepsy; however, known epilepsy genes had lower p values relative to the rest of the protein-coding genes (p=5·8 × 10-8) that were lower than expected from a random sampling of genes. INTERPRETATION:We identified excess ultra-rare variation in known epilepsy genes, which establishes a clear connection between the genetics of common and rare, severe epilepsies, and shows that the variants responsible for epilepsy risk are exceptionally rare in the general population. Our results suggest that the emerging paradigm of targeting of treatments to the genetic cause in rare devastating epilepsies might also extend to a proportion of common epilepsies. These findings might allow clinicians to broadly explain the cause of these syndromes to patients, and lay the foundation for possible precision treatments in the future. FUNDING:National Institute of Neurological Disorders and Stroke (NINDS), and Epilepsy Research UK

Réconciliation du monde et christologie cosmique

Allmen Daniel von. Réconciliation du monde et christologie cosmique. In: Revue d'histoire et de philosophie religieuses, 48e année n°1,1968. pp. 32-45