3,210 research outputs found

    Evaluation of Road Roughness and Road Deterioation

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    There are two road condition survey methods commonly used, the roughness-based equipment such as NAASRA and the distress and severity type road evaluation method as presented by ASTM D-6433. The objective of the study is to evaluate the relationship between road condition obtained from roughness type equipment and road distress. To achieve the objective, a condition survey using the two methods were performed on two road segments in the East Java Provincial road system. Data obtained from the field was evaluated to obtain International Roughness Index (from NAASRA) and Present Condition Index value (from field condition survey). The results show that the two methods provide a comparable result when the distress type is of un-even surface such as rutting and bumping. A slight different result is observed when the major distress occurred in the road is of crack-type such as fatigue and block cracking

    Creep modelling of 316H stainless steel over a wide range of stress

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    Abstract Investigation of material creep behaviour in the diffusion controlled creep regime is often unfeasible because of the long duration associated with low stress levels. On the other side, extrapolation from higher creep rates usually provides inaccurate results because of the sharp change in the data trend as a result of the change in the governing deformation mechanism from dislocation to diffusion type controlled creep. Similarly, extrapolation based on creep models, which have been formulated and validated mainly for dislocation type creep (such power law creep with the creep exponent ranging from 6 to 9), underestimates the actual creep rate significantly. Recently, Bonora and Esposito (2010) developed a mechanism-based model (BE model) capable to account for deformation and damage mechanism occurring in creep. In this work the BE model was applied to AISI 316H stainless steel for which considerable creep data in both dislocation and diffusion temperature/stress controlled regime were available. Using the same data set, the predictive capabilities of several models were compared

    Health-related quality of life and functional changes in DMD:A 12-month longitudinal cohort study

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    Family caregivers of people with amyotrophic lateral sclerosis (ALS) live stressful lives in which they spend most of their time caring for their loved ones and managing difficult situations, thereby reducing the time spent in taking care of themselves. This situation may last several years. Previous literature has widely highlighted that this situation reduces caregivers' quality of life and increases their psychological distress and risk of health problems, but there is a lack of studies that focus on psychological interventions for these situations. This qualitative study examined a pilot experience of two mutual support groups for family caregivers of people with ALS. The aim was to identify caregivers' needs, the prominent aspects of their experience, and to understand whether and how this intervention strategy might help them. Six partners (four men and two women) and six adult children (five women and one man) participated in the groups, which were conducted in northern Italy. After the support groups finished, participants underwent semi-structured interviews. The authors conducted a content analysis of the transcripts of the interviews and the 20 group sessions. The thematic areas identified were "caregiving," "being the son/daughter of a person with ALS," "being the partner of a person with ALS," "group experience" and "group evaluation." The caregiving experience was profoundly different depending on whether the caregiver was a son/daughter or a partner of a patient with ALS. Moreover, comparison with peers and mutual support helped participants to better cope with ALS and its consequences, to improve their care for their relatives and to overcome typical caregiver isolation. These results suggest the usefulness of involving communities in caregiver support in order to create new networks and activate personal and social resources for well-being

    Prospective study on nanoparticle albumin-bound paclitaxel in advanced breast cancer. Clinical results and biological observations in taxane-pretreated patients

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    Background: There is a deep need to improve the care of metastatic breast cancer (MBC) patients, since even today it remains an incurable disease. Taxanes are considered the most effective cytotoxic drugs for the treatment of MBC, both in monotherapy and in combined schedules, but the need for synthetic solvents contributes to the severe toxicities and may have a negative impact on the efficacy. Nanoparticle albumin-bound paclitaxel (Nab-paclitaxel) is a colloidal suspension of paclitaxel and human serum albumin initially developed to avoid the toxicities associated with conventional taxanes. Patients and methods: The aim of this prospective, single-center open-label, noncomparative study was to evaluate the efficacy and safety of nab-paclitaxel in MBC patients pretreated with taxanes. The patients were treated with nab-paclitaxel as a single agent, 260 mg/m2 on day 1 of each 3-week cycle or 125 mg/m2 weekly. The primary endpoint was the overall response rate (ORR). Secondary objectives were duration of response, clinical benefit rate, progression-free survival (PFS), overall survival, and safety. Results: A total of 42 patients (median age 48 years, median Eastern Cooperative Oncology Group performance status 0, triple-negative MBC 19%, all pretreated with a taxane-based therapy, mainly in advanced disease) were enrolled in the study. The ORR was 23.8%, including one complete response (2.4%) and nine partial responses (21.4%); the disease control rate was 50%. The median duration of response was 7.2 months. After a median follow-up of 9 months, the median PFS was 4.6 months. ORR and PFS were similar irrespective of the previous chemotherapy lines, metastatic sites, and biomolecular expression. Nab-paclitaxel was well tolerated, and the most frequent treatment-related toxicities were mild to moderate (grades 1–2). Conclusion: This real-life study shows that nab-paclitaxel has a significant antitumor activity and a manageable safety profile in patients pretreated with taxanes and experiencing a treatment failure after at least one line of chemotherapy

    Laparoscopic versus open distal gastrectomy for locally advanced gastric cancer in middle–low-volume centers in Western countries. a propensity score matching analysis

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    Background: Gastrectomy with D2 lymphadenectomy is the standard treatment for patients with resectable gastric cancer. Laparoscopic distal gastrectomy (LDG) is routinely performed for early gastric cancer, and its indications are increasing even for locally advanced gastric cancer. The aim of this study is to compare two middle–low-volume centers in Western countries experience on LDG versus open distal gastrectomy (ODG) for locally advanced gastric cancer in terms of surgical and oncological outcomes. Methods: We reviewed the data of 123 consecutive patients that underwent LDG and ODG with D2 lymphadenectomy between 2009 and 2014. Among them, 91 were eligible for inclusion (46 LDG and 45 ODG). After propensity score matching analysis, using a 1:1 case-control match, 34 patients were stratified for each group. Results: The mean operative time was significantly longer in the LDG group (257.2 vs. 197.2, p < 0.001). No differences were observed in terms of intraoperative blood loss, average number of lymph nodes removed, and lymph node metastases. The postoperative morbidity was comparable in the two groups. LDG group had a significant faster bowel canalization and soft oral intake (p < 0.001). The 5-year overall and disease-free survival were higher for patients treated by laparoscopy, but the post-hoc subgroups analysis revealed that the advantage of LDG was significant just in N0 and stage IB-II patients, whereas N+ and stage III patient’s survival curves were perfectly superimposable. Conclusions: LDG for locally advanced gastric cancer seems to be feasible and safe with surgical and long-term oncological outcomes comparable with open surgery, even in medium–low-volume centers

    Genetic modifiers of Duchenne muscular dystrophy and dilated cardiomyopathy

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    OBJECTIVE: Dilated cardiomyopathy (DCM) is a major complication and leading cause of death in Duchenne muscular dystrophy (DMD). DCM onset is variable, suggesting modifier effects of genetic or environmental factors. We aimed to determine if polymorphisms previously associated with age at loss of independent ambulation (LoA) in DMD (rs28357094 in the SPP1 promoter, rs10880 and the VTTT/IAAM haplotype in LTBP4) also modify DCM onset. METHODS: A multicentric cohort of 178 DMD patients was genotyped by TaqMan assays. We performed a time-to-event analysis of DCM onset, with age as time variable, and finding of left ventricular ejection fraction 70 mL/m2 as event (confirmed by a previous normal exam < 12 months prior); DCM-free patients were censored at the age of last echocardiographic follow-up. RESULTS: Patients were followed up to an average age of 15.9 \ub1 6.7 years. Seventy-one/178 patients developed DCM, and median age at onset was 20.0 years. Glucocorticoid corticosteroid treatment (n = 88 untreated; n = 75 treated; n = 15 unknown) did not have a significant independent effect on DCM onset. Cardiological medications were not administered before DCM onset in this population. We observed trends towards a protective effect of the dominant G allele at SPP1 rs28357094 and recessive T allele at LTBP4 rs10880, which was statistically significant in steroid-treated patients for LTBP4 rs10880 (< 50% T/T patients developing DCM during follow-up [n = 13]; median DCM onset 17.6 years for C/C-C/T, log-rank p = 0.027). CONCLUSIONS: We report a putative protective effect of DMD genetic modifiers on the development of cardiac complications, that might aid in risk stratification if confirmed in independent cohorts

    Predicting lymphoma development in patients with Sjögren's syndrome

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    ABSTRACTIntroduction: The issue of predicting lymphoma in primary Sjogren's syndrome (pSS) starts from its clinical and biologic essence, i.e., an autoimmune exocrinopathy with sicca syndrome, infl..

    Activity of drugs against dormant Mycobacterium tuberculosis.

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    Objective/background: Heterogeneous mixtures of cellular and caseous granulomas coexist in the lungs of tuberculosis (TB) patients, with Mycobacterium tuberculosis (Mtb) existing from actively replicating (AR) to dormant, nonreplicating (NR) stages. Within cellular granulomas, the pH is estimated to be less than 6, whereas in the necrotic centres of hypoxic, cholesterol/triacylglycerol-rich, caseous granulomas, the pH varies between 7.2 and 7.4. To combat TB, we should kill both AR and NR stages of Mtb. Dormant Mtb remodels lipids of its cell wall, and so lipophilic drugs may be active against NR Mtb living in caseous, lipid-rich, granulomas. Lipophilicity is expressed as logP, that is, the logarithm of the partition coefficient (P) ratio P octanol/P water. In this study, the activity of lipophilic drugs (logP>0) and hydrophilic drugs (logP ≤0) against AR and NR Mtb was measured in hypoxic conditions under acidic and slightly alkaline pHs. Methods: The activity of drugs was determined against AR Mtb (5-day-old aerobic cells: A5) and NR Mtb (12- and 19-day-old hypoxic cells: H12 and H19) in a Wayne dormancy model of Mtb H37Rv at pH 5.8, to mimic the environment of cellular granulomas. Furthermore, AR and NR bacilli were grown for 40 days in Wayne models at pH 6.6, 7.0, 7.4, and 7.6, to set up conditions mimicking the caseous granulomas (hypoxia+slightly alkaline pH), to measure drug activity against NR cells. Mtb viability was determined by colony-forming unit (CFU) counts. Results: At pH 5.8, lipophilic drugs (rifampin, rifapentine, bedaquiline, PA-824, clofazimine, nitazoxanide: logP ≥2.14) reduced CFU of all cells (H12, H19, and A5) by ≥2log10. Among hydrophilic drugs (isoniazid, pyrazinamide, ethambutol, amikacin, moxifloxacin, metronidazole: logP ≤0.01), none reduced H12 and H19 CFUs by ≥2log10, with the exception of metronidazole. When Mtb was grown at different pHs the following Mtb growth was noted: at pH 6.6, AR cells grew fluently while NR cells grew less, with a CFU increase up to Day 15, followed by a drop to Day 40. AR and NR Mtb grown at pH 7.0, 7.4, and 7.6 showed up to 1 log10 CFU lower than their growth at pH 6.6. The pHs of all AR cultures tended to reach pH 7.2–7.4 on Day 40. The pHs of all NR cultures remained stable at their initial values (6.6, 7.0, 7.4, and 7.6) up to Day 40. The activity of drugs against H12 and H19 cells was tested in hypoxic conditions at a slightly alkaline pH. Under these conditions, some lipophilic drugs were more active (>5 log CFU decrease after 21 days of exposure) against H12 and H19 cells than clofazimine, nitazoxanide, isoniazid, pyrazinamide, amikacin (<1 log CFU decrease after 21 days of exposure). Testing of other drugs is in progress. Conclusion: Lipophilic drugs were more active than hydrophilic agents against dormant Mtb in hypoxic conditions at pH 5.8. The Wayne model under slightly alkaline conditions was set up, and in hypoxic conditions at a slightly alkaline pH some lipophilic drugs were more active than other drugs against NR Mtb. Overall, these models can be useful for testing drug activity against dormant Mtb under conditions mimicking the environments of cellular and caseous granulomas
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