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Repeated gesturing on touchscreen computing devices has become part of professional, personal, or school use by persons of all ages. Few studies have compared kinematics among joint motions and gestures during touchscreen interaction. We aimed to quantify the relative contributions of the shoulder, elbow and wrist to completion of several gestures to aid understanding of touchscreen ergonomics. Joint angles of the shoulder, elbow, and wrist were recorded for 22 seated participants while they interacted with a 10.1″ tablet computer held on an easel. Joint excursions at the shoulder, elbow, and wrist were all on average ≤20° during touchscreen interaction. The greatest excursion measured was shoulder rotation for swipe right with a mean of 15.5(±6.0)°. Index finger tap on a touchscreen was completed by participants with less than 5° of mean joint excursion at the shoulder, elbow and wrist. Tap, pinch and stretch gestures demonstrated significantly more wrist flexion/extension (p 0.05) than shoulder flexion/extension, ab/adduction and rotation. Also, swipe left, right and up involved more shoulder rotation (p 0.05) than wrist flexion/extension. These results suggest that when gestures are repeated frequently, the relative risk of overuse injury at the shoulder, elbow, or wrist may depend on the gesture being repeated.

Introduction/Background We compared muscle activation during in- and out-of-water gait of SCI patients to understand the influence of the aquatic ambient on rehabilitation programme. Material and method Twenty healthy subjects and 20 SCI patients were enrolled. All patients had retained walking ability (AIS C and D, lesion level C4-L2, age 18–70 years) and could ambulate indipendently for a minimum of 5 m with or without walking aids. We analyzed, with an surface 8 channel wireless EMG, the following muscles of the right leg: rectus femoris, vastus medialis, vastus lateralis, gluteus maximus, gluteus medius, biceps femoris, tibialis anterior, gastrocnemius medialis. Results In both healthy and affected subjects in water the walking speed decreases whereas the duration of gait cycle increases. Furthermore in SCI patients we found out an increase of the swing phase. Comparing in- and out-of-water results for SCI subjects the maximum muscle activation peak in water occurred before than on dry land; at the opposite in healthy subjects we registered that the maximum muscle activation peak occurred earlier out of the pool. Conclusion The in-water gait cycle is much more similar between SCI and healthy subjects than the out-of-water one. These results suggest that aquatic ambient could positively influence muscle recruitment in SCI patient. Moreover these data give us the opportunity to design water-based exercises that can enrich the tailored rehabilitation programme for every patient.

e18759Background: Clinical cancer trials suffer from underrepresentation of racial and ethnic minorities as well as subjects with low socioeconomic status (SES). Here we examine if these disparitie...

Colon cancer comprises a small population of cancer stem cells (CSC) that is responsible for tumor maintenance and resistant to cancer therapies, possibly allowing for tumor recapitulation once treatment stops. We previously demonstrated that such chemoresistance is mediated by autocrine production of IL-4 through the up-regulation of antiapoptotic proteins. Several innate and adaptive immune effector cells allow for the recognition and destruction of cancer precursors before they constitute the tumor mass. However, cellular immune-based therapies have not been experimented yet in the population of CSCs. Here, we show that the bisphosphonate zoledronate sensitizes colon CSCs to Vγ9Vδ2 T cell cytotoxicity. Proliferation and production of cytokines (TNF-α and IFN-γ) and cytotoxic and apoptotic molecules (TRAIL and granzymes) were also induced after exposure of Vγ9Vδ2 T cells to sensitized targets. Vγ9Vδ2 T cell cytotoxicity was mediated by the granule exocytosis pathway and was highly dependent on isoprenoid production by of tumor cells. Moreover, CSCs recognition and killing was mainly TCR mediated, whereas NKG2D played a role only when tumor targets expressed several NKG2D ligands. We conclude that intentional activation of Vγ9Vδ2 T cells by zoledronate may substantially increase antitumor activities and represent a novel strategy for colon cancer immunotherapy.

The potent anti-tumour activities of gamma delta T cells have prompted the development of protocols in which gamma delta-agonists are administered to cancer patients. Encouraging results from small Phase I trials have fuelled efforts to characterize more clearly the application of this approach to unmet clinical needs such as metastatic carcinoma. To examine this approach in breast cancer, a Phase I trial was conducted in which zoledronate, a V gamma 9V delta 2 T cell agonist, plus low-dose interleukin (IL)-2 were administered to 10 therapeutically terminal, advanced metastatic breast cancer patients. Treatment was well tolerated and promoted the effector maturation of V gamma 9V delta 2 T cells in all patients. However, a statistically significant correlation of clinical outcome with peripheral V gamma 9V delta 2 T cell numbers emerged, as seven patients who failed to sustain V gamma 9V delta 2 T cells showed progressive clinical deterioration, while three patients who sustained robust peripheral V gamma 9V delta 2 cell populations showed declining CA15-3 levels and displayed one instance of partial remission and two of stable disease, respectively. In the context of an earlier trial in prostate cancer, these data emphasize the strong linkage of V gamma 9V delta 2 T cell status to reduced carcinoma progression, and suggest that zoledronate plus low-dose IL-2 offers a novel, safe and feasible approach to enhance this in a subset of treatment-refractory patients with advanced breast cancer.

Imatinib mesylate (imatinib), a competitive inhibitor of the BCR-ABL tyrosine kinase, is highly effective against chronic myelogenous leukemia (CML) cells. However, because 20–30% of patients affected by CML display either primary or secondary resistance to imatinib, intentional activation of Vγ9Vδ2 T cells by phosphoantigens or by agents that cause their accumulation within cells, such as zoledronate, may represent a promising strategy for the design of a novel and highly innovative immunotherapy capable to overcome imatinib resistance. In this study, we show that Vγ9Vδ2 T lymphocytes recognize, trogocytose, and efficiently kill imatinib-sensitive and -resistant CML cell lines pretreated with zoledronate. Vγ9Vδ2 T cell cytotoxicity was largely dependent on the granule exocytosis- and partly on TRAIL-mediated pathways, was TCR-mediated, and required isoprenoid biosynthesis by zoledronate-treated CML cells. Importantly, Vγ9Vδ2 T cells from patients with CML can be induced by zoledronate to develop antitumor activity against autologous and allogeneic zoledronate-treated leukemia cells, both in vitro and when transferred into immunodeficient mice in vivo. We conclude that intentional activation of Vγ9Vδ2 T cells by zoledronate may substantially increase their antileukemia activities and represent a novel strategy for CML immunotherapy.

In humans, the selective depletion of CD8+ cells may prevent GVHD after allogeneic transplantation. These cells can infiltrate and damage target tissues. It is of interest to investigate the phenotypical characteristics and cytotoxic properties of the different CD8+ subsets in cGVHD patients. In a preliminary study we found that patients with cGVHD had a markedly elevated percentage of peripheral blood CCR7−/CD45RA+ cells compared to patients without cGVHD; conversely, the CCR7+/CD45RA+ subsets of CD8+ cells was significantly decreased. In this study, we report in depth on the phenotype of effector T cell subsets in cGVHD patients, as well as their proliferative capability, cytotoxic properties and cellular turnover. We confirm a predominance of effector T cell subsets in cGVHD patients and show that a large fraction of these cells down-regulate CCR7 and re-express CD45RA, thus approaching end-stage differentiation. Moreover CD8+ cells of cGVHD patients have low CD8 coreceptor expression, reduced proliferative potential and a high content of perforin and granzyme A. They also have a lower cell turnover and have more propensity to apoptosis, as demonstrated by BrdU incorporation. Taken together, our findings indicate a perturbation of the balance between naive/memory and effector/CD45RA+ CD8+ T cells, and suggest an involvement of the latter compartment characterized by a high content of cytotoxic equipment, in the pathogenesis of cGVHD.

This paper describes an exploratory case-study of information retrieval practices in one specific discipline, materials science and engineering. In particular, we examine how do the information retrieval practices of practicing professionals compare to those of undergraduate seniors? The preliminary findings provide provisional insights into the concrete retrieval skills students have and need, and suggest teaching practices (particularly in design courses) faculty can employ to help students build such skills.

This document describes the results of a DOE funded joint effort of Membrane Technology and Research Inc. (MTR), SRI International (SRI), and ABB Lummus (ABB) to develop facilitated transport membranes for olefin/paraffin separations. Currently, olefin/paraffin separation is done by distillation—an extremely energy-intensive process because of the low relative volatilities of olefins and paraffins. If facilitated transport membranes could be successfully commercialized, the potential energy savings achievable with this membrane technology are estimated to be 48 trillion Btu per year by the year 2020. We discovered in this work that silver salt-based facilitated transport membranes are not stable even in the presence of ideal olefin/paraffin mixtures. This decline in membrane performance appears to be caused by a previously unrecognized phenomenon that we have named olefin conditioning. As the name implies, this mechanism of performance degradation becomes operative once a membrane starts permeating olefins. This project is the first study to identify olefin conditioning as a significant factor impacting the performance of facilitated olefin transport membranes. To date, we have not identified an effective strategy to mitigate the impact of olefin conditioning. other than running at low temperatures or with low olefin feed pressures. In our opinion, this issue must be addressed before further development of facilitated olefin transport membranes can proceed. In addition to olefin conditioning, traditional carrier poisoning challenges must also be overcome. Light, hydrogen, hydrogen sulfide, and acetylene exposure adversely affect membrane performance through unwanted reaction with silver ions. Harsh poisoning tests with these species showed useful membrane lifetimes of only one week. These tests demonstrate a need to improve the stability of the olefin complexing agent to develop membranes with lifetimes satisfactory for commercial application. A successful effort to improve membrane coating solution stability resulted in the finding that membrane performance loss could be reversed for all poisoning cases except hydrogen sulfide exposure. This discovery offers the potential to extend membrane lifetime through cyclic regeneration. We also found that certain mixed carriers exhibited greater stability in reducing environments than exhibited by silver salt alone. These results offer promise that solutions to deal with carrier poisoning are possible. The main achievement of this program was the progress made in gaining a more complete understanding of the membrane stability challenges faced in the use of facilitated olefin transport membranes. Our systematic study of facilitated olefin transport uncovered the full extent of the stability challenge, including the first known identification of olefin conditioning and its impact on membrane development. We believe that significant additional fundamental research is required before facilitated olefin transport membranes are ready for industrial implementation. The best-case scenario for further development of this technology would be identification of a novel carrier that is intrinsically more stable than silver ions. If the stability problems could be largely circumvented by development of a new carrier, it would provide a clear breakthrough toward finally recognizing the potential of facilitated olefin transport. However, even if such a carrier is identified, additional development will be required to insure that the membrane matrix is a benign host for the olefin-carrier complexation reaction and shows good long-term stability.

The increasing evidence that γδ T cells have potent antitumor activity suggests their value in immunotherapy, particularly in areas of unmet need such as metastatic carcinoma. To this end, we initiated a phase I clinical trial in metastatic hormone-refractory prostate cancer to examine the feasibility and consequences of using the γδ T-cell agonist zoledronate, either alone or in combination with low-dose interleukin 2 (IL-2), to activate peripheral blood γδ cells. Nine patients were enlisted to each arm. Neither treatment showed appreciable toxicity. Most patients were treated with zoledronate + IL-2, but conversely only two treated with zoledronate displayed a significant long-term shift of peripheral γδ cells toward an activated effector-memory–like state (TEM), producing IFN-γ and perforin. These patients also maintained serum levels of tumor necrosis factor–related apoptosis inducing ligand (TRAIL), consistent with a parallel microarray analysis showing that TRAIL is produced by γδ cells activated via the T-cell receptor and IL-2. Moreover, the numbers of TEM γδ cells showed a statistically significant correlation with declining prostate-specific antigen levels and objective clinical outcomes that comprised three instances of partial remission and five of stable disease. By contrast, most patients treated only with zoledronate failed to sustain either γδ cell numbers or serum TRAIL, and showed progressive clinical deterioration. Thus, zoledronate + IL-2 represents a novel, safe, and feasible approach to induce immunologic and clinical responses in patients with metastatic carcinomas, potentially providing a substantially increased window for specific approaches to be administered. Moreover, γδ cell phenotypes and possibly serum TRAIL may constitute novel biomarkers of prognosis upon therapy with zoledronate + IL-2 in metastatic carcinoma. [Cancer Res 2007;67(15):7450–7]

In this study we have evaluated the in vitro effects of four different aminobisphosphonates, alendronate, risedronate, neridronate and zoledronate, on Vγ9Vδ2 T cell activation and differentiation. All tested aminobisphosphonates induce an IL-2-dependent activation and expansion of Vγ9Vδ2 T lymphocytes in primary PBMC cultures of healthy donors. Most notably, they also determine a different distribution of Vγ9Vδ2 T cell subsets, with decrease of Tnaive and TCM cells and increase of TEM and TEMRA Vγ9Vδ2 cells, indicating that in vitro treatment with aminobisphosphonates induces Vγ9Vδ2 T lymphocytes to differentiate towards an effector/cytotoxic phenotype. Accordingly, Vγ9Vδ2 T lymphocytes cultured with aminobisphosphonates and IL-2 showed a major content of IFN-γ and acquired the ability to kill tumor target cells.

Among the late effects of hematopoietic stem cell transplantation (HSCT), chronic graft-vs-host disease (cGVHD) still remains as the major determinant of long-term outcome and quality of life. The disease typically appears between 3 months to 1.5 years following an allogeneic transplantation and is characterized by symptoms similar to those of autoimmune disease.

The objectives of this project were to develop feasible synthetic routes to produce (1) 4(4{prime}-hydroxy-5{prime}6{prime},7{prime}8{prime}-tetrahydro-1{prime}-naphthylmethyl)-6-methyldibenzothiophene, and (2) a 1-hydroxynaphthalene-dibenzothiophene polymer. These compounds are thought to be representative of sulfur containing molecules in coal. The program was divided into two technical tasks. Unfortunately, the attempted syntheses of these compounds was unsuccessful due to their unusual reactivities. Attempted synthetic routes and possible future routes are described, and Appendix A lists the compounds that were synthesized during this program.

Introduction: The imbalance in the coagulative function can increase the risk of bleeding in cirrhotic patients after hepatic surgery; as no data or specific guidelines are available, prophylaxis of venous thromboembolism could be hazardous. Objective: To assess the effect of venous thrombosis prophylaxis after hepatic resection for hepatocellular carcinoma (HCC) in cirrhotic patients. Patients and Methods: 229 consecutive cirrhotic patients with HCC who underwent hepatic resection over a 10-year period were retrospectively evaluated to assess whether there was any difference in the incidence of thrombotic or hemorrhagic complications between those who received prophylaxis with lowmolecular weight heparin and those who did not. Differences and possible effect of the following parameters were investigated: age, sex, Child–Pugh and MELD score, platelet count, presence of esophageal varices, type of hepatic resection, duration of surgery, intraoperative transfusion of blood and fresh-frozen plasma (FFP), body mass index (BMI), diabetes and previous cardiovascular disease. Results: 157 out of 229 (68.5%) patients received antithromboembolic prophylaxis (group A) while the other 72 (31.5%) did not (group B). Patients in group B had higher Child–Pugh and MELD scores, lower platelet counts, a higher prevalence of esophageal varices and higher requirements of intraoperative transfusion of FFP. Incidence of venous thromboembolism and postoperative hemorrhage was respectively 0.63% and 3.18 in group A and 1.38% and 1.38% in group B; these differences were not significant. None of the variables analyzed including prophylaxis proved to be risk factors for venous thromboembolism while only the presence of esophageal varices was associated with an increased risk of bleeding. Conclusions: Prophylaxis is safe in cirrhotic patients without esophageal varices; its real need has to be better assessed.

Twenty-three patients who had undergone surgery for non-neoplastic pathologies of the terminal choledochus were studied using 99mTc Br-IDA. This method is used to study patients operated for PST of CDS because: 1) is not invasive and does not cause allergies; 2) it allows a physiological evaluation of biliary flow to be obtained; 3) it is not influenced by the patient's body structure, by the presence of intestinal gas or costo-chondral calcification; 4) the radiation dose absorbed by the patient is very low; 5) it does not require any special preparation of the patient. Papillosphincterotomy was performed in 16 patients and choledochoduodenostomy in 7 patients. Follow-up varied between a minimum of two and maximum of eight years. The morphology of the biliary tract remained normal in all cases or was only slightly dilated. Captation and excretion time remained within normal values. Marker activity in the duodenum appeared early in all cases. A duodenogastric reflux was only observed in one patient among those undergoing PST, whereas it was observed almost constantly following CDS.

The gastric emptying has been studied with 99Tc labelled in 35 patients followed for 2-8 years after duodenogastric resection. All patients had been undergone a gastric resection of 2/3 of stomach. In 18 had been performed a Billroth II (BII) and in 17 a gastrojejunostomy with a Roux-en-Y anastomosis. The jejunal loop had been carried out about 25-35 cm from the Treitz, the mesenteric margin isolated for 2-3 cm and the jejunojejunostomy performed about 50 cm from the gastrojejunostomy. Nobody complained symptoms from altered gastric emptying. In all patients with Roux-en-Y anastomosis there was an intense radioactivity in the new stoma till the 150th minute, and peristaltic activity was valid and coordinated. In patients with BII there was no radioactivity in the new stoma before the 150th minute, and peristaltic activity was always convulsive and uncoordinated.

The objectives of this project are to develop feasible synthetic routes to produce (1) 4(4`-hydroxy-5`,6`,7`,8`-tetrahydro-l`-naphthylmethyl )- 6-methyldibenzothiophene, and (2) a 1-hydroxynaphthalene-benzothiophene polymer. Our experimental work during this quarter concentrated on. As several possible synthetic routes to the target molecule, 4(4`-hydroxy-5`,6`,7`,8`-tetrahydro- l`-naphthylmethyl )-6-methyldibenzothiophene. We tried synthesizing the intermediates for our first method, in which we couple a metalated 4-methyldibenzothiophene with 4-formyl-5,6,7,8-tetrahydro-1-naphthol. We found that we could easily metalate dibenzothiophene, and then add a methyl group to the 4-position to give 4-methyldibenzothiophene in greater than 80% yield by using t-butyllithium in tetrahydropyran followed by dimethylsulfate. However, adding the second metal to the desired 4` position using the same method was more difficult, and instead the reaction occurred on the methyl group. Therefore, we will investigate an alternative method, in which a hydroxy group is added in order to help direct the second metalation step to the 4` position on 4-methyldibenzothiophene.

The objectives of this project are to develop feasible synthetic routes to produce (1) 4(4{prime}- hydroxy- 5{prime},6{prime},7{prime},8{prime}- tetrahydro-1{prime}- naphthylmethyl)- 6-methyl dibenzothiophene, and (2) a 1-hydroxy naphthalene- dibenzothiophene polymer. These compounds are thought to be representative of sulfur containing molecules in coal. The program is divided into three tasks, the first of which is a project work plan that we have already submitted. Our experimental work during this quarter concentrated on Task 2: Synthesis of 4(4{prime}- hydroxy- 5{prime},6{prime},7{prime},8{prime}- tetrahydro-1{prime}- naphthylmethyl)- 6-methyldibenzothiophene. 11 refs.

Three cases of leiomyosarcomas of the small bowel, two localized in the jejunum and one in the ileum are reported. In the light of reported data, stress is laid on the anatomicopathological aspects and it is pointed out that the symptomatology is not specific and is comparable to that characterising the other neoplasms of the small bowel. The usefulness of the various diagnostic investigations are analysed and it is maintained that surgery plays a primary role in the treatment of such neoformations. It is maintained, finally, that further studies are needed to pinpoint the factors that may be correlated with the prognosis.

The role of aminophylline in the re-formation of peritoneal adhesions was considered in 23 rats. Since the adhesions were obtained, the animals were subsequently divided into three groups, the first one containing seven units, the others containing eight animals each. During the four days prior the surgery, allopurinol at the dose of 50 mg/kg/die was added to the regular ground laboratory chow in the animals of the second group; aminophylline at the dose of 40 mg/kg/die was administered four hours and immediately prior the surgery, to the animals of the third group. The adhesions that we observed, were graded and evaluated assigning them a score. At the moment of the lysis of adhesions, we observed the score of 2.71 +/- 1.11 in the first group, 3.12 +/- 1.13 in the second group, and 2.75 +/- 1.03 in the third one. Matching each group one another no statistically significant difference was found. At the end the experiment, we observed a score of 3.71 +/- 0.49 for the adhesions in the first group, 2 +/- 0.75 in the second group, and 3.87 +/- 0.35 in the third one. Matching these scores with those observed at the moment of their lysis, they appeared significantly higher in the animals of the first group (p less than 0.02) and of the third group (p less than 0.05), but they were lower in the second group (p less than 0.05). Such results indicate that the re-formation of peritoneal adhesions following their lysis is constant, that allopurinol decreases the intensity of the process, while aminophylline increases it.

Background The purpose of this study was to describe fractures sustained by children and to analyze the associated costs when a caretaker falls down stairs while holding a child. Materials and methods Between 2004 and 2012, 16 children who sustained a fracture after a fall down stairs while being carried by a caregiver were identified. Parents/caregivers were interviewed to see how the fall occurred, and a cost analysis was performed. Results The average age of the patients was 14.5 months (7–51 months). The lower extremity was involved in 15 of 16 fractures, with 8 involving the femur. The majority were buckle fractures, but all diaphyseal femur fractures were spiral. Three patients required a reduction in the operating room. All fractures healed with cast immobilization. Five patients underwent skeletal surveys, as the treating physicians were concerned about potential child abuse. The average cost of treatment was $6785 (range $948–45,876). Detailed histories from the caregivers showed that they “missed a step” due to the child being carried in front of the caregiver, obscuring their vision. Conclusions A fall in a caregiver's arms while going down stairs can result in multiple orthopedic injuries. The costs of treating these injuries are not insignificant, and the suspicion of child abuse can be both costly and unnecessary in the case of a true accident. While descending the stairs with a child in their arms, the caregiver should hold the child to the side so as not to obscure their vision of the step with one arm, ideally holding the handrail with the other. Level of evidence IV case series.

A case of cancer of the small bowel associated with Crohn's disease with onset 21 years after the first clinical signs of the latter is reported. The patient survived for 20 months after cancer diagnosis. After noting the rare association between the two conditions, the aetiopathogenetic relations that can be called on to explain relations of causality are analysed and it is emphasised that it is impossible to distinguish symptoms from those of cancer due to the renewed inflammatory activity. Finally it is considered that to clarify unequivocably the relations between the two conditions further studies are required.

Cancer of the small bowel observed at the 1st Surgical Clinic of Palermo University between 1964 and 1985 have been examined. In the light of reported data, the various factors that might explain the low frequency are analysed, stress being laid on the fact that non-pathognomonic clinical features present considerable diagnostic problems for an early diagnosis. The primary role of surgery in the treatment of such cancers is emphasised.