Timing resolution studies of the optical part of the AFP Time-of-flight detector.

We present results of the timing performance studies of the optical part and front-end electronics of the time-of-flight subdetector prototype for the ATLAS Forward Proton (AFP) detector obtained during the test campaigns at the CERN-SPS test-beam facility (120 GeV π+ particles) in July 2016 and October 2016. The time-of-flight (ToF) detector in conjunction with a 3D silicon pixel tracker will tag and measure protons originating in central exclusive interactions p + p → p + X + p, where the two outgoing protons are scattered in the very forward directions. The ToF is required to reduce so-called pileup backgrounds that arise from multiple proton interactions in the same bunch crossing at high luminosity. The background can fake the signal of interest, and the extra rejection from the ToF allows the proton tagger to operate at the high luminosity required for the measurement of the processes. The prototype detector uses fused silica bars emitting Cherenkov radiation as a relativistic particle passes through them. The emitted Cherenkov photons are detected by a multi-anode micro-channel plate photomultiplier tube (MCP-PMT) and processed by fast electronics.

Construction of the optical part of a time-of-flight detector prototype for the AFP detector.

We present the construction of the optical part of the ToF (time-of-flight) subdetector prototype for the AFP (ATLAS Forward Proton) detector. The ToF detector in conjunction with a 3D silicon pixel tracker will tag and measure protons originating in central exclusive interactions p + p → p + X + p, where the two outgoing protons are scattered in the very forward directions. The ToF is required to reduce so-called pileup backgrounds that arise from multiple proton interactions in the same bunch crossing at high luminosity. The background can fake the signal of interest, and the extra rejection from the ToF allows the proton tagger to operate at the high luminosity required for measurement of the processes. The prototype detector uses fused silica bars emitting Cherenkov radiation as a relativistic particle passes through it. The emitted Cherenkov photons are detected by a micro-channel plate multi-anode Photomultiplier Tube (MCP-PMT) and processed by fast electronics.

Amnion-derived multipotent progenitor cells support allograft tolerance induction.

Donor-specific immunological tolerance using high doses of bone marrow cells (BMCs) has been demonstrated in mixed chimerism-based tolerance induction protocols; however, the development of graft versus host disease remains a risk. Here, we demonstrate that the co-infusion of limited numbers of donor unfractionated BMCs with human amnion-derived multipotent progenitor cells (AMPs) 7 days post-allograft transplantation facilitates macrochimerism induction and graft tolerance in a mouse skin transplantation model. AMPs + BMCs co-infusion with minimal conditioning led to stable, mixed, multilineage lymphoid and myeloid macrochimerism, deletion of donor-reactive T cells, expansion of CD4(+)CD25(+)Foxp3(+) regulatory T cells (T(regs)) and long-term allograft survival (>300 days). Based on these findings, we speculate that AMPs maybe a pro-tolerogenic cellular therapeutic that could have clinical efficacy for both solid organ and hematopoietic stem cell transplant applications.

The elastic modulus, percolation, and disaggregation of strongly interacting, intersecting antiplane cracks.

We study the modulus of a medium containing a varying density of nonintersecting and intersecting antiplane cracks. The modulus of nonintersecting, strongly interacting, 2D antiplane cracks obeys a mean-field theory for which the mean field on a crack inserted in a random ensemble is the applied stress. The result of a self-consistent calculation in the nonintersecting case predicts zero modulus at finite packing, which is physically impossible. Differential self-consistent theories avoid the zero modulus problem, but give results that are more compliant than those of both mean-field theory and computer simulations. For problems in which antiplane cracks are allowed to intersect and form crack clusters or larger effective cracks, percolation at finite packing is expected when the shear modulus vanishes. At low packing factor, the modulus follows the dilute, mean-field curve, but with increased packing, mutual interactions cause the modulus to be less than the mean-field result and to vanish at the percolation threshold. The "nodes-links-blobs" model predicts a power-law approach to the percolation threshold at a critical packing factor of p(c) = 4.426. We conclude that a power-law variation of modulus with packing, with exponent 1.3 drawn tangentially to the mean-field nonintersecting relation and passing through the percolation threshold, can be expected to be a good approximation. The approximation is shown to be consistent with simulations of intersecting rectangular cracks at all packing densities through to the percolation value for this geometry, p(c) = 0.4072.

Retinoic acid and vitamin E modulate expression and release of CD178 in carcinoma cells: consequences for induction of apoptosis in CD95-sensitive cells.

CD178 (CD95-ligand) is expressed on several tumor cells and likely influences the interaction of the tumor with the host immune system. However, little is known about the mechanisms that regulate its expression on the cell surface. We have evaluated the ability of various compounds and cytokines to regulate cell surface expression and release of soluble CD178 in various carcinoma cell lines. Vitamin E succinate (VES) and retinoic acid (RA) were found to reduce CD178 surface expression, whereas interferon-gamma stimulated a slight upregulation. At 48 h, the regulation of surface CD178 by VES and RA arose from a small decrease in CD178 mRNA and to a greater extent due to an increase in the release of soluble CD178; the latter was blocked by addition of a metalloproteinase inhibitor. Accordingly, VES and RA treatment diminished the ability of tumor cells to kill CD95-sensitive cells and this effect was markedly reduced by the presence of a metalloproteinase inhibitor. Our results indicate that, in vitro, CD178 expression on the cell surface of tumor cells can be regulated by agents that alter both expression and release of the ligand. In vivo, such treatments may play an important role in the outcome of tumor sensitivity or resistance to host immune mechanisms.

Stimulation of inflammatory responses in vitro and in vivo by lipophilic HMG-CoA reductase inhibitors.

The enzyme 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase catalyses the rate limiting step in cholesterol biosynthesis and is markedly inhibited by the statin family of drugs. The effect of statins on lipid lowering is clearly defined, but the ability of the drugs to directly regulate inflammatory functions has not been well explored. In this report, we show that there are differences among the statins in their capacity to induce proinflammatory responses both in human monocytes in vitro, and in leukocytes in mice in vivo. Treatment of human monocytes with lipophilic statins alone stimulated the production of MCP-1, IL-8, TNF-alpha and IL-1 beta and markedly sensitized the cells to subsequent challenge with inflammatory agents. Lipophilic statins also increased the production of reactive oxygen species in monocytes. In contrast, pretreatment of cells with the hydrophilic pravastatin did not induce these heightened inflammatory responses. Furthermore, treatment of mice with lipophilic statins caused a markedly higher influx of leukocytes into the inflamed peritoneal cavity following challenge with thioglycollate. Overall, these results demonstrate that the lipophilic statins influence a regulatory pathway in monocytes that controls cytokine production and that the statins induce different pro-inflammatory responses both in vitro and in vivo.

Life history attributes of Indian meal moth (Lepidoptera: Pyralidae) and Angoumois grain moth (Lepidoptera: Gelechiidae) reared on transgenic corn kernels.

The Indian meal moth, Plodia interpunctella (Hübner), and Angoumois grain moth, Sitotroga cerealella (Olivier), are two globally distributed stored-grain pests. Laboratory experiments were conducted to examine the impact that corn (Zea mays L.) kernels (i.e., grain) of some Bacillus thuringiensis Berliner (Bt) corn hybrids containing CrylAb Bt delta-endotoxin have on life history attributes of Indian meal moth and Angoumois grain moth. Stored grain is at risk to damage from Indian meal moth and Angoumois grain moth; therefore, Bt corn may provide a means of protecting this commodity from damage. Thus, the objective of this research was to quantify the effects of transgenic corn seed containing CrylAb delta-endotoxin on Indian meal moth and Angoumois grain moth survival, fecundity, and duration of development. Experiments with Bt grain, non-Bt isolines, and non-Bt grain were conducted in environmental chambers at 27 +/- 1 degrees C and > or = 60% RH in continuous dark. Fifty eggs were placed in ventilated pint jars containing 170 g of cracked or whole corn for the Indian meal moth and Angoumois grain moth, respectively. Emergence and fecundity were observed for 5 wk. Emergence and fecundity of Indian meal moth and emergence of Angoumois grain moth were significantly lower for individuals reared on P33V08 and N6800Bt, MON 810 and Bt-11 transformed hybrids, respectively, than on their non-Bt transformed isolines. Longer developmental times were observed for Indian meal moth reared on P33V08 and N6800Bt than their non-Bt-transformed isolines. These results indicate that MON 810 and Bt-11 CrylAb delta-endotoxin-containing kernels reduce laboratory populations of Indian meal moth and Angoumois grain moth. Thus, storing Bt-transformed grain is a management tactic that warrants bin scale testing and may effectively reduce Indian meal moth and Angoumois grain moth populations in grain without application of synthetic chemicals or pesticides.

Seed mixtures as a resistance management strategy for European corn borers (Lepidoptera: Crambidae) infesting transgenic corn expressing Cry1Ab protein.

Dispersal of neonate European corn borers, Ostrinia nubilalis (Hübner), in seed mixtures of transgenic corn expressing Cry1Ab protein (Bt+) and nontransgenic corn (Bt-) was evaluated in a 2-yr field study. The main objective was to determine if larval dispersal limits the effectiveness of seed mixtures as a resistance management strategy. Mixtures evaluated included (1) all Bt+ plants, (2) every fifth plant Bt- with remaining plants Bt+, (3) every fifth plant Bt+ with remaining plants Bt-, and (4) all Bt- plants. The transformation events MON 802 (B73 BC1F2 x Mol7) and MON 810 (B73 BC1F1 x Mo17), which express the Cry1Ab endotoxin isolated from Bacillus thuringiensis subsp. kurstaki, were used as the sources of Bt+ seed in 1994 and 1995, respectively (YieldGard, Monsanto, St. Louis, MO). At corn growth stage V6-V8, subplots within each mixture (15-20 plants each) were infested so that every fifth plant in mixtures 1 and 4, every Bt- plant in mixture 2, and every Bt+ plant in mixture 3 received two egg masses. Larval sampling over a 21-d period indicated increased neonate dispersal off of Bt+ plants, reduced survival of larvae that dispersed from Bt+ plants to Bt- plants, and a low incidence of late-instar movement from Bt- plants to Bt+ plants. Computer simulations based on mortality and dispersal estimates from this study indicate that seed mixtures will delay the evolution of resistant European corn borer populations compared with uniform planting of transgenic corn. However, resistant European corn borer populations likely will develop faster in seed mixes compared with separate plantings of Bt and non-Bt corn.

The results of in situ prosthetic replacement for infected aortic grafts.

BACKGROUND: Treatment of aortic graft infection with graft excision and axillofemoral bypass may carry an increased risk of limb loss, aortic stump blowout, and pelvic ischemia. A review of patients with aortic graft infection treated with in situ prosthetic graft replacement was undertaken to determine if mortality, limb loss, and reinfection rates were improved with this technique. METHODS: The clinical data of 25 patients, 19 males and 6 females, with a mean age of 68 years (range 35 to 83), with aortic graft infection, treated between January 1, 1989, and December 31, 1998, by in situ prosthetic graft replacement were reviewed. Follow-up was complete in the 23 surviving patients and averaged 36 months (range 4 to 103). RESULTS: Twenty aortofemoral, 3 aortoiliac, and 2 straight aortic graft infections were treated with excision and in situ replacement with standard polyester grafts in 16 patients (64%), or with rifampin-soaked collagen or gelatin-impregnated polyester grafts in 9 patients (36%). Fifteen patients (60%) had aortic graft enteric fistulas, 8 patients (32%) had abscesses or draining sinuses, and 2 patients (8%) had bacterial biofilm infections. Thirty-day mortality was 8% (2 of 25). There were no early graft occlusions or amputations. There was one late graft occlusion. There were no late amputations. The reinfection rate was 22% (5 grafts). All reinfections occurred in patients operated upon for occlusive disease. Only one reinfection occurred in the rifampin-soaked graft group (11% versus 29%, P = NS). Reinfection tended to be lower in patients with aortoenteric fistulas and without abscess. Autogenous tissue coverage provided statistically significant protection against reinfection. There were no late deaths related to in situ graft infection. CONCLUSIONS: Patients treated with in situ graft replacement had an 8% mortality and 100% limb salvage rate. Reinfection rates were similar to those of extra-anatomic bypass, but a trend of lower reinfection rates with rifampin-impregnated grafts was apparent. Patients with aortoenteric fistula and without abscess appear to be well treated by the technique of in situ prosthetic grafting and autogenous tissue coverage.

Hyperplastic gastric polyp causing progressive gastric outlet obstruction.

Hyperplastic polyps represent 75 to 90% of gastric polypoid lesions. The manifestations of these unique gastric neoplasms vary, including abdominal pain, nausea, and vomiting or gastrointestinal bleeding. The vast majority of these lesions are small, asymptomatic, and found incidentally on radiologic evaluation or endoscopic examination of the upper gastrointestinal tract. Herein we describe a large, benign, pedunculated hyperplastic polyp that led to progressive gastric outlet obstruction. In addition, we provide an overview of gastric polyps and a review of the literature. Excision of gastric polyps by endoscopic or surgical means is recommended as prudent treatment to eliminate occurrence of malignant foci.

Aorto-caval and ilio-iliac arteriovenous fistulae.

BACKGROUND: To determine optimal management of major abdominal arteriovenous fistulae and define factors affecting outcome. METHODS: We reviewed clinical data of 18 patients, 16 males and 2 females, who underwent repair of major abdominal arteriovenous fistulae between 1970 and 1997. RESULTS: Sixteen patients had primary fistula, caused by rupture of an atherosclerotic aortic or aortoiliac aneurysm into the inferior vena cava (IVC), iliac, or left renal vein. Two had secondary, iatrogenic arteriovenous fistulae. Seventeen patients (94%) were symptomatic, 11 (62%) had acute presentation. Fistula was diagnosed preoperatively in 8 (44%). Fistula closure (direct suture 16, patch 1, iliac vein ligation 1) was followed by aortoiliac reconstruction in all patients. Caval clip was placed in 3 patients. Early mortality was 6%; 7 patients had major complications. During follow-up (mean 6.1 years) 2 patients died of causes related to fistula closure. CONCLUSIONS: Rupture of aortoiliac aneurysms into the iliac veins or IVC carries a better prognosis than intraperitoneal, retroperitoneal, or enteric rupture. Although preoperative diagnosis is ideal, a high index of suspicion, careful repair avoiding pulmonary embolization, and blood salvage were all helpful in keeping morbidity and mortality low. Our data suggest that IVC interruption is seldom warranted.

Chronic appendicitis: does it exist?

The typical presentation of acute appendicitis is well known. A few patients, however, have had an atypical clinical course suggestive of recurrent appendiceal inflammation, which has been confirmed by appendectomy. Therefore, in the evaluation of a patient with abdominal pain, a history of similar episodes should not preclude a diagnosis of appendicitis.

Medicolegal aspects of athletic head injury.

This article reviews the legal aspects of head injuries resulting from a variety of athletic activities, focusing primarily on head and brain injuries resulting from the playing of football, boxing, horseback riding, winter sports (hockey and skiing), and soccer. Part 1 give a general overview of the occurrence of head injuries in athletics and the potential for litigation. Part 2 reviews the history of and increase in sports injury litigation, as well as resulting changes in the law. In Part 3, the current status of athletic head injury litigation, the parties involved, types of claims brought, and viable defenses are discussed. Finally, Part 4 reviews different ways to reduce athletic head injury litigation through better equipment design and adequate warning and instructions for users and coaches.

Medicolegal aspects of athletic cervical spine injury.

Approximately 10,000 Americans suffer catastrophic cervical spinal cord injuries each year. Most are caused by automobile accidents; however, many of these crippling injuries are related to participation in sports. This article evaluates the legal aspects of neck injury resulting from participation in a number of athletic events, including football, wrestling, gymnastics, snow skiing, ice hockey, diving, and surfing.

Human monocytic cells contain high levels of intracellular Fas ligand: rapid release following cellular activation.

Human monocytes express both Fas and Fas ligand (FasL) on the cell surface, and the interaction of these molecules induces spontaneous apoptosis. In this report we present a study of monocytic cells by FACS and confocal microscopy using anti-FasL Abs that reveals high levels of preformed FasL within the intracellular compartment. Further analysis by immunoblotting of cell cytoplasmic proteins confirmed the presence of a 37-kDa protein recognized by anti-FasL Abs. Stimulation of the monocytic cells with immune complexes, PHA, or superantigen gave rise to the rapid release of soluble FasL from within the cells. The presence of high levels of FasL within human monocytes suggests that, upon stimulation, the cells can rapidly translocate intracellular FasL to the cell surface and release it into the extracellular milieu. These findings indicate a novel mechanism for monocytes to respond rapidly to environmental changes, resulting in the release of active, soluble FasL.

Differential induction of apoptosis by Fas-Fas ligand interactions in human monocytes and macrophages.

Human monocytes undergo spontaneous apoptosis upon culture in vitro; removal of serum from the media dramatically increases the rate of this process. Monocyte apoptosis can be significantly abrogated by the addition of growth factors or proinflammatory mediators. We have evaluated the role of the endogenous Fas-Fas ligand (FasL) interaction in the induction of this spontaneous apoptosis and found that a Fas-immunoglobulin (Ig) fusion protein, an antagonistic anti-Fas monoclonal antibody and a rabbit anti-FasL antibody all greatly reduced the onset of apoptosis. The results indicate that spontaneous death of monocytes is mediated via an autocrine or paracrine pathway. Treatment of the cells with growth factors or cytokines that prevented spontaneous apoptosis had no major effects on the expression of Fas or FasL. Additionally, monocyte-derived macrophages were found to express both Fas and FasL but did not undergo spontaneous apoptosis and were not sensitive to stimulation by an agonistic anti-Fas IgM. These results indicate that protective mechanisms in these cells exist at a site downstream of the receptor-ligand interaction.

Abdominal pain and irritable bowel syndrome in adolescents: a community-based study.

OBJECTIVES: This study was undertaken to determine (1) the prevalence of gastrointestinal symptoms including abdominal pain in a community-based population of adolescents, (2) whether a subgroup of these subjects have symptoms resembling Irritable bowel syndrome (IBS), and (3) whether anxiety and depression are more commonly found in adolescents with IBS-type symptoms compared with unaffected adolescents. METHODS: We collected data by administration of a gastrointestinal symptoms questionnaire, State-Trait Anxiety Inventory, and Children's Depression Inventory to middle school and high school students. RESULTS: A total of 507 subjects participated (mean age of middle school students 12.6 years; mean age of high school students 15.6 years). Abdominal pain was noted by 75% of all students. The pain occurred weekly in 13% to 17% of the subjects and was severe enough to affect activities in approximately 21%. Irritable bowel syndrome-type symptoms were noted by 17% of high school students and 8% of middle school students (p <0.01) who reported abdominal pain (n = 381), representing 14% and 6% of all high school and middle school students (p <0.005), respectively. Anxiety and depression scores were significantly higher for students with IBS-type symptoms compared with those without symptoms. Eight percent of all students had seen a physician for abdominal pain in the previous year. These visits were correlated with abdominal pain severity, frequency, duration, and disruption of normal activities but not with anxiety, depression, gender, family structure, or ethnicity. CONCLUSION: Recurrent abdominal pain and symptoms of IBS are commonly noted in a community-based adolescent population and frequently result in use of health care resources. Health care providers who work with this age group need to be able to recognize the symptom complex associated with IBS, as well as the possible relationship to anxiety and depression.

Epidemiology of Munchausen syndrome by proxy, non-accidental poisoning, and non-accidental suffocation.

A two year prospective study was performed to determine the epidemiology of Munchausen syndrome by proxy, non-accidental poisoning, and non-accidental suffocation in the UK and the Republic of Ireland. Cases were notified to the British Paediatric Association Surveillance Unit from September 1992 to August 1994 if a formal case conference had been held for the first time during that period to discuss any of the above conditions. A total of 128 cases were identified: 55 suffered Munchausen syndrome by proxy alone, 15 poisoning, and 15 suffocation; 43 suffered more than one type of abuse. The majority of children were aged under 5 years, the median age being 20 months. On 85% of occasions the perpetrator was the child's mother. In 42% of families with more than one child, a sibling had previously suffered some form of abuse. Eighty five per cent of notifying paediatricians considered the probability of their diagnosis as virtually certain before a case conference was convened. The commonest drugs used to poison were anticonvulsants; opiates were the second commonest. Sixty eight children suffered severe illness of whom eight died. The combined annual incidence of these conditions in children aged under 16 years is at least 0.5/100,000, and for children aged under 1, at least 2.8/100,000.