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Contains fulltext : 288035.pdf (Publisher’s version ) (Open Access) BACKGROUND: T1 colorectal cancer (CRC) without histological high-risk factors for lymph node metastasis (LNM) can potentially be cured by endoscopic resection, which is associated with significantly lower morbidity, mortality and costs compared to radical surgery. An important prerequisite for endoscopic resection as definite treatment is the histological confirmation of tumour-free resection margins. Incomplete resection with involved (R1) or indeterminate (Rx) margins is considered a strong risk factor for residual disease and local recurrence. Therefore, international guidelines recommend additional surgery in case of R1/Rx resection, even in absence of high-risk factors for LNM. Endoscopic full-thickness resection (eFTR) is a relatively new technique that allows transmural resection of colorectal lesions. Local scar excision after prior R1/Rx resection of low-risk T1 CRC could offer an attractive minimal invasive strategy to achieve confirmation about radicality of the previous resection or a second attempt for radical resection of residual luminal cancer. However, oncologic safety has not been established and long-term data are lacking. Besides, surveillance varies widely and requires standardization. METHODS/DESIGN: In this nationwide, multicenter, prospective cohort study we aim to assess feasibility and oncological safety of completion eFTR following incomplete resection of low-risk T1 CRC. The primary endpoint is to assess the 2 and 5 year luminal local tumor recurrence rate. Secondary study endpoints are to assess feasibility, percentage of curative eFTR-resections, presence of scar tissue and/or complete scar excision at histopathology, safety of eFTR compared to surgery, 2 and 5 year nodal and/or distant tumor recurrence rate and 5-year disease-specific and overall-survival rate. DISCUSSION: Since the implementation of CRC screening programs, the diagnostic rate of T1 CRC is steadily increasing. A significant proportion is not recognized as cancer before endoscopic resection and is therefore resected through conventional techniques primarily reserved for benign polyps. As such, precise histological assessment is often hampered due to cauterization and fragmentation and frequently leads to treatment dilemmas. This first prospective trial will potentially demonstrate the effectiveness and oncological safety of completion eFTR for patients who have undergone a previous incomplete T1 CRC resection. Hereby, substantial surgical overtreatment may be avoided, leading to treatment optimization and organ preservation. Trial registration Nederlands Trial Register, NL 7879, 16 July 2019 ( https://trialregister.nl/trial/7879 ).

A talk given in Hamburg about bilingualism and young children's language awareness&nbsp

Sotolensis keltoni sp. nov. (Figs 1���5) HOLOTYPE : MEXICO: Durango: ��� 5 mi W of Durango [24.03325 �� N 104.73274 �� W] Dgo. MEX. 6500��� [198 m] 14 June 1964 L.A. Kelton; sotol [Dasylirion sp. (Asparagaceae), det. field id]���, 1;m (AMNH _ PBI 00418775). Holotype Sotolensis keltoni n. sp. det. K.L. Menard & M.D. Schwartz, 2018 [red label]. Deposited in the collection of the Instituto de Biologia, Universidad Nacional Autonoma de Mexico, Mexico City, D.F. (IBUNAM). Paratypes: MEXICO: Durango: 5 mi W of Durango, 24.03325 �� N 104.73274 �� W, 198 m, 11 Jun 1964, H. F. Howden, Dasylirion sp. (Asparagaceae), det. field id, 6;m (00418784���00418789), 27;f (00418790���00418804, 00420079���00420090) (CNC), 1;f (00418747) (UOSN), 1;m (00418753), 1;f (00418754) (USNM); 14 Jun 1964, L.A. Kelton, Dasylirion sp. (Asparagaceae), det. field id, 22;m (00418755���00418774, 0 0 418776, 00418777), 33;f (00420111���00420143) (CNC), 3;m (00418746, 0 0 418748, 00418749), 3;f (00418750���00418752) (UOSN). Durango, 24.0333 �� N 104.6667 �� W, 1890 m, 22 Jun 1964, L.A. Kelton, 2;m (00418781, 00418782), 2;f (00420091, 00420092) (AMNH), 4;m (00418778���00418780, 00418783), 18;f (00420093���00420110) (CNC). DIAGNOSIS : Same as generic diagnosis. DESCRIPTION : Coloration, surface, vestiture, structure, and genitalia: As in generic description. MEASUREMENTS : MALE (holotype /range; N=4): total body length 2.46/2.55-2.70, clypeus to cuneus length 1.75/1.70-1.90, body width 1.06/1.10-1.30, pronotal length 0.43/0.45, head width 0.81/ 0.75-0.83, pronotal width 0.98/0.85-1.00, antennal segment lengths: AS I 0.35/0.40, AS II 0.60/0.60-0.65, AS III 0.35/0.35-0.37, AS IV 0.36/ 0.35, and interocular distance 0.47/0.45-0.47. FEMALE (range; N=3): total body length 2.2���2.65, clypeus to cuneus length 1.6-1.9, pronotal length 0.45-0.47, head width 0.83-0.87, pronotal width 0.93-0.97, antennal segment lengths: AS I 0.40-0.43, AS II 0.6-0.63, AS III 0.35-0.37, AS IV 0.35, and interocular distance 0.45-0.5. ETYMOLOGY : Named after the late Leonard A. Kelton, whose work in Durango, Mexico, led to the capture of these specimens. HOST : The majority of the specimens collected of this species were labeled as collected on sotol, genus Dasylirion sp. (Asparagales: Asparagaceae: Notinoideae). There are currently about 22 species of sotol, of which two are known from Durango: D. durangense Trel., and D. simplex Trel. (WSCP 2018). This group of plants is native to Mexico, all have tough leaves with serrated edges that provide a natural defense., Published as part of Menard, K. L. & Schwartz, M. D., 2018, A description of a new genus and new species of sotol-feeding Eccritotarsini (Hemiptera: Heteroptera: Miridae: Bryocorinae) from Durango, Mexico, pp. 283-292 in Zootaxa 4514 (2) on pages 287-288, DOI: 10.11646/zootaxa.4514.2.11, http://zenodo.org/record/2607852

Sotolensis gen. nov. (Figs 1���5) Type species: Sotolensis keltoni sp. nov. DIAGNOSIS : Recognized by small size, large eyes with posterior margin overlapping anterior margin of pronotum, deep punctation on posterior margin of pronotum, weakly developed tubercle on dorso-lateral margin of gonopore in males, presence of a supragenital bridge, and presence of modified dorsal surface of ventral labiate plate forming spines in females. DESCRIPTION : MALE : COLORATION: Dorsum primarily castaneous with whitish-yellow and dark brown markings on pronotum and hemelytron, venter dark brown; clypeus and labrum brown (Fig. 1A); antennal segments I and II pale castaneous, segment II paler medially, or sometimes pale on apical one third; antennal segment III pale castaneous basally, dark castaneous distally; segment IV dark castaneous; pronotal collar yellowcastaneous, calli and area between calli dark castaneous, posterior lobe of pronotum cream, propleuron orangecastaneous; metepimeron pale brown to castaneous, remainder of thorax dark brown; mesoscutum and scutellum dark castaneous with dark longitudinal medial stripe; coxae and femora pale castaneous, tibiae yellow, tarsal segments pale yellow transitioning to dark brown towards claws; hemelytron primarily cream with anterior one third of clavus transitioning to darker brown, corium pale brown at base, dark brown medially, and approximately posterior one-third cream, costal margin primarily castaneous with posterior one-fourth lightening to cream, cuneus dark brown; membrane within cell dark brown, pale cream posteriad of cell, veins dark brown; pregenital abdominal segment dark brown. SURFACE AND VESTITURE: Head, pronotal collar, calli and anterior or pronotum smooth and weakly shiny; reminder of pronotum, scutellum and hemelytron matte; thoracic pleura and abdomen shiny, smooth to weakly rugose; head, pronotum, except anterior margin of collar, mesoscutum, scutellum, and base of clavus punctate; each puncture bearing a recessed seta. Dorsum and appendages with dense, relatively short, semi-adpressed pale simple setae (Fig. 3A); thoracic pleura with a few similar setae; abdomen with dense simple setae; tibial spines absent, tibiae with dense pale simple setae only. STRUCTURE: Body short and parallel sided, macropterous. Head: (Figs 2 A���D) Comparatively large compared with body, nearly as long as wide and high, almost triangular in frontal view, clypeus and frons anterior to eyes prominent in lateral view; vertex broad and weakly convex; frons strongly convex; clypeus prominent, oriented ventroposteriorly, clearly differentiated from mandibular plates and labrum; mandibular plate broadly triangular; maxillary plate rectangular, twice as long as high; buccula short, merging behind base of labium; gula reduced, one half length of buccula; eyes small, less than half height of head in lateral view, not stylate, posterior margins projecting beyond collar and anterolateral margins of pronotum; antennal fossa located slightly above ventral margin of eye; antennal segment I thickest segment, narrowing just at joint with antennal fossa; antennal segment II thin with width increasing distally to match approximate width of first; segments III and IV filiform; labium thick, reaching to base of abdomen, segment IV short, nearly twice as long as broad at base, apically blunt. Thorax: (Figs 2A, B) Pronotum trapeziform, lateral margins strongly concave, posterior angles rounded, posterior margin weakly convex; pronotal collar demarcated by flat surface anteriad of calli, nonpunctate portion of collar short and narrow, width approximately equal to diameter of antennal segments III or IV; calli weakly raised, not touching medially; posterior lobe of pronotal disc only slightly raised; peritreme of metathoracic scent-gland lanceolate, extended posteriorly along ventral margin of metapleuron; evaporative area reduced to narrow falciform area along dorsal margin of peritreme, with scalloped surface devoid of characteristic mushroom bodies (Fig. 3B); separation between mesoscutum and scutellum denoted by short suture on extreme lateral margin; scutellum weakly bulbous at apex, somewhat depressed in middle. Legs: All femora comparatively short, cylindrical, hind femur not swollen; tibiae straight and rather short; hind femora with trichobothria (tb) deeply recessed, tuberculate and trichoma well developed (Fig. 3C); tarsus three segmented, segments I���III almost equal in length, combined II and III slightly fusiform (Fig 2D), III with long guard setae. Pretarsus: (Figs 3D, E) Claw falcate, strongly and gradually curved (cl); inner surface of claw with large subquadrate pulvillus (pul), ventral surface with fringe of very small trichia; pulvillar comb of 5 relatively large trichia behind each pulvillus (pulcmb); parempodia asymmetrical, with outer parempodium reduced, shorter than inner (par) [of 9 pretarsi examined with SEM, all apices broken]. Hemelytron: Opaque, corium with nearly straight lateral margin, R+M vein weakly demarcated and terminating at approximate median of corium; costal vein indented at basal one-half of length; cuneus as long as wide; membrane with single cell not surpassing apex of cuneus. GENITALIA: Pygophore: Comparatively large, about half of abdomen, short, about twice as wide as long, with base partly retracted into abdominal segment VIII (Fig. 3F); dorsal wall straight, with quadrate tergal process on posterior edge of aperture (Fig. 4B); ventral wall strongly sloping and extending caudally; subgenital plate with internal process protruding medial to right paramere insertion (Fig. 4B); left lateral margin of pygophore opening with weakly developed tubercle; supragenital bridge present (Fig. 4B); aperture of genital capsule wide; plane of phallic structures turned slightly more than 20��. Parameres: Left paramere: Small, weakly scythe-shaped (Figs 3E, F, 4E). Right paramere: Large, long, L-shaped with the apex hook-like (Figs 3E, F, 4C, D), in repose placed behind tubercle of pygophore (Fig 3E). Aedeagus: Small and simple; eversible, projecting ventrad through supragenital bridge. Phallobase: With well-developed capitate processes (Fig 4F, G). Phallotheca: Dorsal and ventral walls sclerotized, ventral wall expanded apically, approximately twice as long as dorsal wall (Fig 4G, H). Ductus seminis: Attached to middle of phallobase, proximal one third with rings, distal two thirds sclerotized, narrow, approximately as long as ventral wall of phallotheca, base swollen, apical portion needlelike, enclosed in thin transparent membrane projecting free of main endosomal membrane (Fig 4 F���H; mds); opening of secondary gonopore simple, without ring-like structure (Fig 4G, H; 2 ��gp). Endosoma: (or vesica sensu Konstantinov 2000) Small, wrinkled, predominately membranous with apex sclerotized, cap-like (Fig 4 F���H; mpes). FEMALE : COLORATION: Specimens with reduced membrane without dark median patch of coloration on corium. SURFACE AND VESTITURE: As in male. STRUCTURE: Hemelytron with varying degrees of wing membrane reduction and shortening of the cuneus (Figs 1 B���D). GENITALIA: Posterior margin of sternite 7: With broad triangular projection, reaching posteriad one-half length of lateral margins (Fig 5A). Dorsal wall of genital chamber: Dorsal sac: Membranous, small, pediculate, located posteriorly; anterior margin terminates even with posterior end of ventral labiate plates. Dorsal labiate plate and sclerotized rings absent. Lateral oviducts: Short, attached contiguously. Spermathecal gland: Attached posteriad of oviducts. Seminal depository: Posterior margin begins level with posterolateral margins of ventral labiate plate, continues anteriorly as thin clear membranous bag spanning length and width of sclerotized portion of bursa copulatrix, extending anteriorly for length equal to length of bursa copulatrix as slightly thicker winkled sac; lateral surface of anterior portion of seminal depository with two large thin rings with wavy border (Fig 5D). Vestibular sclerites: Formed by strongly sclerotized, asymmetrical left and right sides of ventral labiate plate (Fig 5E) and base of left first gonapophysis (Fig 5F); apical portion of left ventral labiate plate with spinelike anterior and posterior apices; right ventral labiate plate with spinelike apex; base of left first gonapophysis with ventroposterior tubercle. Medial surface of rami membranous, extending ventroanteriad and forming thickened membranous border of vulva (Fig 5G). Posterior wall: Membranous without interramal lobes or sclerites; covering anterior surface of ovipositor base and large sclerotized prominence on anterior surface of ovipositor base (Fig 5 H���J). Gonapophyses: First: Gradually tapering, with outer surface clothed with dense minute teeth. Second: Apically twisted, with peculiar row of large teeth on inner surface and finely dentate outer surface (Fig 5B, C)., Published as part of Menard, K. L. & Schwartz, M. D., 2018, A description of a new genus and new species of sotol-feeding Eccritotarsini (Hemiptera: Heteroptera: Miridae: Bryocorinae) from Durango, Mexico, pp. 283-292 in Zootaxa 4514 (2) on pages 284-286, DOI: 10.11646/zootaxa.4514.2.11, http://zenodo.org/record/2607852, {"references":["Konstantinov, F. V. (2000) Stroenie genital'nogo apparata samtsov klopov-slepnyakov (Heteroptera: Miridae) i ego znachenie dlya nadrodovoj klassifikatsii. [Structure of the male genitalia in plant bugs (Heteropetra: Miridae) and its bearing to suprageneric classification]. PhD thesis, St Petersburg State University, St Petersburg, 179 pp."]}

Background: Recurrent type 1 and 2 microdeletions of NF1 (neurofibromatosis, type 1) gene leads to a more severe phenotype than heterozygous point mutations. The associated deletion of RNF135 (Ring Finger protein 135), a flanking NF1 gene, is known to be responsible for the childhood overgrowth syndrome but its implication in tumoral severity has never been proven.Methods and Results: A Single Nucleotide Polymorphisms array (715K) was performed in a patient with a very severe form of type 1 neurofibromatosis, as revealed by massive cervico-mediastinal plexiform neurofibromas. It showed a small 126kb atypical deletion encompassing only RNF135 and the first exon of NF1.Conclusion: This observation highlights the possible role of RNF135 in tumoral severity in type 1 neurofibromatosis caused by recurrent type 1 and type 2 microdeletions.

Prolyl endopeptidase (PREP) is a phylogenetically conserved serine protease and, in humans and rodents, is highly expressed in the brain. Several neuropeptides associated with learning and memory and neurodegenerative disorders have been proposed to be the substrates for PREP, suggesting a possible role for PREP in these processes. However, its physiological function remains elusive. Combining genetic, anatomical, electrophysiological, and behavioral approaches, we show that PREP genetrap mice have decreased synaptic spine density in the CA1 region of the hippocampus, reduced hippocampal long-term potentiation, impaired hippocampal-mediated learning and memory, and reduced growth-associated protein-43 levels when compared with wild-type controls. These observations reveal a role for PREP in mediating hippocampal plasticity and spatial memory formation, with implications for its pharmacological manipulation in diseases related to cognitive impairment.

BACKGROUND: A therapy that slows disease progression is the major unmet need in Parkinson's disease. METHODS: In this double-blind trial, we examined the possibility that rasagiline has disease-modifying effects in Parkinson's disease. A total of 1176 subjects with untreated Parkinson's disease were randomly assigned to receive rasagiline (at a dose of either 1 mg or 2 mg per day) for 72 weeks (the early-start group) or placebo for 36 weeks followed by rasagiline (at a dose of either 1 mg or 2 mg per day) for 36 weeks (the delayed-start group). To determine a positive result with either dose, the early-start treatment group had to meet each of three hierarchical end points of the primary analysis based on the Unified Parkinson's Disease Rating Scale (UPDRS, a 176-point scale, with higher numbers indicating more severe disease): superiority to placebo in the rate of change in the UPDRS score between weeks 12 and 36, superiority to delayed-start treatment in the change in the score between baseline and week 72, and noninferiority to delayed-start treatment in the rate of change in the score between weeks 48 and 72. RESULTS: Early-start treatment with rasagiline at a dose of 1 mg per day met all end points in the primary analysis: a smaller mean (+/-SE) increase (rate of worsening) in the UPDRS score between weeks 12 and 36 (0.09+/-0.02 points per week in the early-start group vs. 0.14+/-0.01 points per week in the placebo group, P=0.01), less worsening in the score between baseline and week 72 (2.82+/-0.53 points in the early-start group vs. 4.52+/-0.56 points in the delayed-start group, P=0.02), and noninferiority between the two groups with respect to the rate of change in the UPDRS score between weeks 48 and 72 (0.085+/-0.02 points per week in the early-start group vs. 0.085+/-0.02 points per week in the delayed-start group, P

Las algas marinas se han consumido en Asia desde tiempos remotos, mientras que en países occidentales su principal aplicación ha sido como agente gelificante y coloide para la industria de alimentos, farmacéutica y cosmética. Las algas son buena fuente de nutrientes como proteínas, vitaminas, minerales y fibra dietética, al respecto, la fibra dietética de algas es particularmente rica en fracción soluble. Si se comparan las algas con vegetales terrestres, se encuentran más componentes beneficiosos para la salud, como ácidos grasos a>-3 y moléculas bioactivas. Las algas sintetizan diversos metabolitos secundarios que presentan actividad antioxidante, antiinflamatoria, anticancerígena y antidiabética. Por lo tanto, las algas se pueden considerar una fuente natural de gran interés ya que contienen compuestos con numerosas actividades biológicas y pueden ser usadas como ingrediente funcional en muchas aplicaciones industriales como en alimentos funcionales.

This chapter draws on the work of the Australian Justice Reinvestment Project (AJRP) (Brown et al., 2015). The AJRP examined the development of justice reinvestment particularly in the context of it’s alignment with broad social justice values. We are also specifically interested in how and whether justice reinvestment can meet the needs of those social groups that have been adversely affected by mass imprisonment and hyper-incarceration, particularly racial and Indigenous minorities, women and people with mental health issues and cognitive impairment (Cunneen et al., 2013). We argue that justice reinvestment was in its early development strongly tied to civil rights, particularly with the focus on imprisonment and racialization, and social justice for communities where large numbers of residents were recycled in and out of prison.

Although liver transplantation is a widely accepted treatment for hepatocellular carcinoma (HCC), much controversy remains and there is no generally accepted set of guidelines. An international consensus conference was held on Dec 2–4, 2010, in Zurich, Switzerland, with the aim of reviewing current practice regarding liver transplantation in patients with HCC and to develop internationally accepted statements and guidelines. The format of the conference was based on the Danish model. 19 working groups of experts prepared evidence-based reviews according to the Oxford classification, and drafted recommendations answering 19 specific questions. An independent jury of nine members was appointed to review these submissions and make final recommendations, after debates with the experts and audience at the conference. This report presents the final 37 statements and recommendations, covering assessment of candidates for liver transplantation, criteria for listing in cirrhotic and non-cirrhotic patients, role of tumour downstaging, management of patients on the waiting list, role of living donation, and post-transplant management.

✓ Patients with Turcot syndrome (TS) are predisposed to colon tumors and primary brain tumors, typically glioblastomas or medulloblastomas. The authors describe a patient with TS featuring a known germline mutation of exon 5 of the hPMS2 mismatch repair gene who developed two metachronous glioblastomas, both with distinct oligodendroglial features. Molecular genetic analysis revealed allelic loss of chromosome 19q in the patient's second tumor but no allelic loss of chromosome 1p. Prominent microsatellite instability was also found in this tumor, consistent with a germline mismatch repair defect. Because this patient had an unusual underlying condition and his tumor had a unique histological appearance for TS, it was hypothesized that this genetic defect may predispose to malignant gliomas with oligodendroglial features. The authors therefore evaluated whether sporadic glioblastomas and oligodendrogliomas undergo mutations of this region of the hPMS2 gene. However, single-strand conformation polymorphism analysis of hPMS2 exon 5 failed to reveal mutations in 20 sporadic glioblastomas and 16 sporadic oligodendroglial gliomas. Thus, although it is possible that the germline hPMS2 exon 5 mutation may predispose to glioblastomas with an oligodendroglial component, the same genetic defect is not commonly involved in sporadic oligodendrogliomas or glioblastomas.

The shift from inpatient to ambulatory settings and the increasingly large and diverse numbers of ambulatory clients require reengineering and cost-effective approaches to managing ambulatory care. With data on 921 encounters in 12 ambulatory clinics, we developed CARE TRACKER, an instrument to describe nursing encounters by type, intervention, staff, time, and cost. Distinguishing nursing from medical interventions is an appreciable improvement over the traditional practice of bundling nursing as part of overhead costs. If managers can track the care delivered, they can better calculate staffing requirements, staff mix, inservice needs, and the costs of their existing and projected services.

This report of the BOOST2012 workshop presents the results of four working groups that studied key aspects of jet substructure. We discuss the potential of the description of jet substructure in first-principle QCD calculations and study the accuracy of state-of-the-art Monte Carlo tools. Experimental limitations of the ability to resolve substructure are evaluated, with a focus on the impact of additional proton proton collisions on jet substructure performance in future LHC operating scenarios. A final section summarizes the lessons learnt during the deployment of substructure analyses in searches for new physics in the production of boosted top quarks., Comment: Report of BOOST2012, held at IFIC Valencia, 23$^{rd}$-27$^{th}$ of July 2012

Crohn's disease and ulcerative colitis, the two common forms of inflammatory bowel disease (IBD), affect over 2.5 million people of European ancestry, with rising prevalence in other populations(1). Genome-wide association studies and subsequent meta-analyses of these two diseases(2,3) as separate phenotypes have implicated previously unsuspected mechanisms, such as autophagy(4), in their pathogenesis and showed that some IBD loci are shared with other inflammatory diseases(5). Here we expand on the knowledge of relevant pathways by undertaking a meta-analysis of Crohn's disease and ulcerative colitis genome-wide association scans, followed by extensive validation of significant findings, with a combined total of more than 75,000 cases and controls. We identify 71 new associations, for a total of 163 IBD loci, that meet genome-wide significance thresholds. Most loci contribute to both phenotypes, and both directional (consistently favouring one allele over the course of human history) and balancing (favouring the retention of both alleles within populations) selection effects are evident. Many IBD loci are also implicated in other immune-mediated disorders, most notably with ankylosing spondylitis and psoriasis. We also observe considerable overlap between susceptibility loci for IBD and mycobacterial infection. Gene co-expression network analysis emphasizes this relationship, with pathways shared between host responses to mycobacteria and those predisposing to IBD.

This is the summary and introduction to the proceedings contributions for the Les Houches 2009 "Tools and Monte Carlo" working group., Comment: 144 Pages. Workshop site http://wwwlapp.in2p3.fr/conferences/LesHouches/Houches2009/ . Conveners were Butterworth, Maltoni, Moortgat, Richardson, Schumann and Skands

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In 2003.5 Eta Carinae was expected to undergo an X-ray eclipse (Damineli et al., 2000). In the framework of an international campaign to obtain multi-wavelength observations of this event, we have obtained optical CCD images of Eta Carinae. Here, we present the B, V, R, I, data of Eta Car obtained before and during the X-ray eclipse., Comment: 4 pages, 3 figures, accepted by IBVS

The ability of rats or mice to withstand the consequences of injury to myelinated axons in the CNS was previously shown to depend on the ability to manifest a T cell-mediated protective immune response, which is amenable to boosting by myelin-specific T cells. Here we show that this ability, assessed by retinal ganglion cell survival after optic nerve injury or locomotor activity after spinal cord contusion, is decreased if the animals were immunized as neonates with myelin proteins (resulting in their nonresponsiveness as adults to myelin proteins) or injected with naturally occurring regulatory CD4 + CD25 + T cells immediately after the injury, and is improved by elimination of these regulatory T cells. In nude BALB/c mice replenished with a splenocyte population lacking CD4 + CD25 + regulatory T cells, significantly more neurons survived after optic nerve injury than in nude mice replenished with a complete splenocyte population or in matched wild-type controls. In contrast, neuronal survival in wild-type BALB/c mice injected with CD4 + CD25 + regulatory T cells immediately after injury was significantly worse than in noninjected controls. These findings suggest that the ability to cope with the sequelae of a CNS insult is affected unfavorably by nonresponsiveness to myelin self-antigens and favorably by conditions allowing rapid expression of an autoimmune response. The regulatory T cells might represent an evolutionary compromise between the need to avoid autoimmune diseases and the need for autoimmunity on alert for the purpose of tissue maintenance.

Two 42-d floor pen studies were conducted with commercial broiler chickens to measure the efficacy of 1 ppm diclazuril in the starter or grower diet in shuttle programs with 66 ppm salinomycin. Study 1 compared a salinomycin to diclazuril (starter to grower diet) shuttle treatment with salinomycin to salinomycin, salinomycin to 100 ppm monensin, salinomycin to 99.8 ppm lasalocid, and unmedicated treatments. Study 2 compared a diclazuril to salinomycin (starter to grower) shuttle treatment with 125 ppm nicarbazin to salinomycin, 79.2 ppm narasin + nicarbazin to salinomycin, 125 ppm zoalene to salinomycin, and unmedicated treatments. Fifty 1-d-old chicks were randomly allotted to each of 10 pens per treatment in each study using a randomized complete block design. Starter (Days 0 to 21) and grower (Days 22 to 37) diets in each study contained 55 ppm bacitracin methylene disalicylate. The finisher diet (Days 38 to 42) in each study was unmedicated. Birds were inoculated via their feed on Day 22 (Study 1) or Day 15 (Study 2) with a mixed inoculum of Eimeria acervulina, Eimeria maxima, and Eimeria tenella. Four birds per pen (two male and two female) were randomly selected in each study for coccidial lesion scores on Day 6 postinoculation. These studies demonstrated that the use of 1 ppm diclazuril in shuttle programs was highly efficacious against a mixed inoculum of Eimeria spp. in comparison with nicarbazin, narasin + nicarbazin, and zoalene in starter diets and salinomycin, monensin, and lasalocid in grower diets.

We consider the exactly soluble Edwards-Wilkinson Model in one dimension and demonstrate explicitly, that it is possible to construct a field, that does not depend explicitly on time, such that the corresponding time dependent correlation function,, is dominated at long times by a stretched exponential decay. The difference between this and the stretched exponential decay present in truly non linear systems is discussed., Comment: 9 pages

Partial injury to the spinal cord can propagate itself, sometimes leading to paralysis attributable to degeneration of initially undamaged neurons. We demonstrated recently that autoimmune T cells directed against the CNS antigen myelin basic protein (MBP) reduce degeneration after optic nerve crush injury in rats. Here we show that not only transfer of T cells but also active immunization with MBP promotes recovery from spinal cord injury. Anesthetized adult Lewis rats subjected to spinal cord contusion at T7 or T9, using the New York University impactor, were injected systemically with anti-MBP T cells at the time of contusion or 1 week later. Another group of rats was immunized, 1 week before contusion, with MBP emulsified in incomplete Freund's adjuvant (IFA). Functional recovery was assessed in a randomized, double-blinded manner, using the open-field behavioral test of Basso, Beattie, and Bresnahan. The functional outcome of contusion at T7 differed from that at T9 (2.9 ± 0.4, n = 25, compared with 8.3 ± 0.4, n = 12; p < 0.003). In both cases, a single T cell treatment resulted in significantly better recovery than that observed in control rats treated with T cells directed against the nonself antigen ovalbumin. Delayed treatment with T cells (1 week after contusion) resulted in significantly better recovery (7.0 ± 1; n = 6) than that observed in control rats treated with PBS (2.0 ± 0.8;n = 6; p < 0.01; nonparametric ANOVA). Rats immunized with MBP obtained a recovery score of 6.1 ± 0.8 (n = 6) compared with a score of 3.0 ± 0.8 (n = 5; p < 0.05) in control rats injected with PBS in IFA. Morphometric analysis, immunohistochemical staining, and diffusion anisotropy magnetic resonance imaging showed that the behavioral outcome was correlated with tissue preservation. The results suggest that T cell-mediated immune activity, achieved by either adoptive transfer or active immunization, enhances recovery from spinal cord injury by conferring effective neuroprotection. The autoimmune T cells, once reactivated at the lesion site through recognition of their specific antigen, are a potential source of various protective factors whose production is locally regulated.

Several hypotheses have explained the beneficial effect of adding bromocriptine (BR) to levodopa (LD) in Parkinson's disease (PD) by interaction at the striatal level. In the present study we show the influence of BR on plasma LD values in an acute loading experiment (125 mg LD + 12.5 mg carbidopa [DCI] given alone and together with 2.5 mg BR at 0 time; 4 h observation). On the basis of this influence we have been able to differentiate between three groups of patients: (a) in six patients (five of them with frequent off episodes) LD values were significantly lower (p less than 0.05) when both drugs were given together (area under the curve [AUC] +/- SE 2.10 +/- 0.42 micrograms/ml/h vs. 4.96 +/- 1.10 micrograms/ml/h); (b) in eight patients (one with frequent akinesia) LD levels were significantly higher (p less than 0.003) when both drugs were given together (AUC +/- SE 4.05 +/- 0.51 micrograms/ml/h vs. 1.94 +/- 0.19 micrograms/ml/h); (c) in six patients (without motor fluctuations) no difference in LD levels was noted (AUC +/- SE 3.91 + 0.62 micrograms/ml/h vs. 3.81 +/- 0.70 micrograms/ml/h). The clinical evaluation (Webster scale) did not show substantial differences, except for increased dyskinesia, which correlated with higher LD levels. In summary, we suggest that the diminution of motor fluctuations and the occurrence of dyskinesias when BR is added to LD may stem from changes in LD plasma levels. These findings would be taken into consideration in the interpretation of therapeutic response fluctuations under combined treatment.

The present investigation was motivated from the consideration that a host environment rich in iron, represented by high serum transferrin saturation (TS) and high serum iron and serum ferritin levels might offer favorable growth conditions for leukemic cells in addition to infection, thus affecting survival. Serum measurements were obtained on 113 pediatric patients with acute lymphoblastic leukemia (ALL), seen at Memorial Sloan-Kettering Cancer Center between May 20, 1981 and August 8, 1983. A significant difference (p less than 0.001) was found between the survival of patients according to whether their first measured TS was greater than 36% or less than 36%, with fewer deaths in the group with TS less than 36. The relationship between TS and survival was still observed when patients were stratified according to length of time from diagnosis, risk group, French-American-British (FAB) classification, or presence of organomegaly at diagnosis (p less than 0.001). Similar differences were observed between survival of patients grouped according to their first measured serum ferritin. These results independently confirm and extend observations presented earlier and support the consideration that motivated this study. The value of serum iron-related measurements as prognostic variables cannot be established from this type of study; however, these findings suggest the need for a prospective study.

We report cytogenetic and DNA studies in three XX males. Two males seemed to have extra chromosomal material on the tip of one X chromosome. All three males were shown to have Y chromosome material as indicated by hybridization of Y-specific DNA probes to genomic DNA. One male was unusual in that as he showed the 15-kb fragment detected by pDP34 that is thought to map close to the Y centromere. It is suggested that this finding might point to an inversion on the Y chromosome.

The reproducible inflammatory changes caused by infection with herpes simplex virus (Eidolon-Virus) in the anterior segment in mice represent a useful model. They are very similar to severe inflammation of the eye, as seen in herpes simplex infection. The method used by the authors to damage the corneal epithelium with a local anesthetic is similar to human pathology, in which a disturbance of the protective function of the corneal epithelium also facilitates infection by herpes simplex virus as well. The changes described are a starting point for further investigations.

During 6 weeks of lithium treatment, the RBC glycine and choline levels of five cognitively impaired geriatric subjects without affective disorders increased significantly and correlated with RBC and plasma lithium levels. The subjects' cognitive processes did not improve.

In March 2012, the Wyoming Department of Health was notified by Natrona County public health officials regarding three patients hospitalized for unexplained acute kidney injury (AKI), all of whom reported recent use of synthetic cannabinoids (SCs), sometimes referred to as "synthetic marijuana." SCs are designer drugs of abuse typically dissolved in a solvent, applied to dried plant material, and smoked as an alternative to marijuana. AKI has not been reported previously in users of SCs and might be associated with 1) a previously unrecognized toxicity, 2) a contaminant or a known nephrotoxin present in a single batch of drug, or 3) a new SC compound entering the market. After the Wyoming Department of Health launched an investigation and issued an alert, a total of 16 cases of AKI after SC use were reported in six states. Review of medical records, follow-up interviews with several patients, and laboratory analysis of product samples and clinical specimens were performed. The results of the investigation determined that no single SC brand or compound explained all 16 cases. Toxicologic analysis of product samples and clinical specimens (available from seven cases) identified a fluorinated SC previously unreported in synthetic marijuana products: (1-(5-fluoropentyl)-1H-indol-3-yl)(2,2,3,3-tetramethylcyclopropyl) methanone, also known as XLR-11, in four of five product samples and four of six patients' clinical specimens. Public health practitioners, poison center staff members, and clinicians should be aware of the potential for renal or other unusual toxicities in users of SC products and should ask about SC use in cases of unexplained AKI.

Biodiversity underpins ecosystem goods and services and hence protecting it is key to achieving sustainability. However, the persistence of many species is threatened by habitat loss and fragmentation due to human land use and climate change. Conservation efforts are implemented under very limited economic resources, and therefore designing scalable, cost-efficient and systematic approaches for conservation planning is an important and challenging computational task. In particular, preserving landscape connectivity between good habitat has become a key conservation priority in recent years. We give an overview of landscape connectivity conservation and some of the underlying graph-theoretic optimization problems. We present a synthetic generator capable of creating families of randomized structured problems, capturing the essential features of real-world instances but allowing for a thorough typical-case performance evaluation of different solution methods. We also present two large-scale real-world datasets, including economic data on land cost, and species data for grizzly bears, wolverines and lynx.