Search

We propose a new implicit–explicit scheme to address the challenge of modeling wave propagation within thin structures using the time‐domain finite element method. Compared to standard explicit schemes, our approach renders a time marching algorithm with a time step independent of the plate thickness and its associated discretization parameters (mesh step and order of approximation). Relying on the standard three dimensional elastodynamics equations, our strategy can be applied to any type of material, either isotropic or anisotropic, with or without discontinuities in the thickness direction. Upon the assumption of an extruded mesh of the plate‐like geometry, we show that the linear system to be solved at each time step is partially lumped thus efficiently treated. We provide numerical evidence of an adequate convergence behavior, similar to a reference solution obtained using the well‐known leapfrog scheme. Further numerical investigations show significant speed up factors compared to the same reference scheme, proving the efficiency of our approach for the configurations of interest. [ABSTRACT FROM AUTHOR]

Enhancing disaster risk reduction (DRR) and community resilience are fundamental for sustainable development. However, cultural and political‐institutional barriers hinder governments from progressing towards sustainability. We propose a redesign of social impact assessment (SIA) to make it more applicable to the field of regional and urban planning, and we discuss the role SIA can have in enhancing community resilience to achieve DRR and sustainable development in localities. We argue that, to convert SIA into a tool that can inform regional recovery and development planning, a rethinking of SIA and of the role of SIA practitioners is needed. We therefore expound the SIA Framework for Action and we enhance it to be a community‐based process focussed on informing regional policies and plans and decisions about the projects to be included in such plans. Application of the SIA Framework for Action will help governments overcome the barriers to DRR and sustainable development. [ABSTRACT FROM AUTHOR]

This special issue contributes to building an integrated social science perspective on resilience and resilience‐building. The articles in this issue provide theoretical reflections and empirical insights on two dimensions that characterize resilience in society. The first (local community dimension) comprises the set of community resources, services, adaptive, transformative and coping capacities, processes, actions and behaviors that enable communities to learn from crises, disasters and past failures and transform toward sustainability in localities (community resilience). The second (governance dimension) comprises the set of adaptive and transformative governance strategies and assessment frameworks that enable social learning and sustainability transformation to be strengthened in localities and scaled up across multiple governance levels (social resilience). This special issue provides a theoretical common‐ground and practical pathways to define resilience and to support recovery and development planning to enhance resilience in society in order to achieve effective disaster risk reduction and climate action for sustainable development. [ABSTRACT FROM AUTHOR]

Lysosomal enzyme deficiency in mucopolysaccharidosis (MPS) I results in glycosaminoglycan (GAG) accumulation leading to pain and limited physical function. Disease‐modifying treatments for MPS I, enzyme replacement, and hematopoietic stem cell therapy (HSCT), do not completely resolve MPS I symptoms, particularly skeletal manifestations. The GAG reduction, anti‐inflammatory, analgesic, and tissue remodeling properties of pentosan polysulfate sodium (PPS) may provide disease‐modifying treatment for musculoskeletal symptoms and joint inflammation in MPS I following ERT and/or HSCT. The safety and efficacy of PPS were evaluated in four subjects with MPS I aged 14–19 years, previously treated with ERT and/or HSCT. Subjects received doses of 0.75 mg/kg or 1.5 mg/kg PPS via subcutaneous injections weekly for 12 weeks, then every 2 weeks for up to 72 weeks. PPS was well tolerated at both doses with no serious adverse events. MPS I GAG fragment (UA‐HNAc [1S]) levels decreased at 73 weeks. Cartilage degradation biomarkers serum C‐telopeptide of crosslinked collagen (CTX) type I (CTX‐I) and type II (CTX‐II) and urine CTX‐II decreased in all subjects through 73 weeks. PROMIS scores for pain interference, pain behavior, and fatigue decreased in all subjects through 73 weeks. Physical function, measured by walking distance and dominant hand function, improved at 49 and 73 weeks. Decreased GAG fragments and cartilage degradation biomarkers, and positive PROMIS outcomes support continued study of PPS as a potential disease‐modifying treatment for MPS I with improved pain and function outcomes. [ABSTRACT FROM AUTHOR]

The aim of this work was to evaluate the resistance of two pathogenic bacteria (Listeria monocytogenes and Salmonella enterica subsp. enterica serotype Senftenberg), and three airborne food‐spoiling filamentous fungi (Hyphopichia burtonii, Penicillium nordicum, and Aspergillus brasiliensis ATCC 16404) to gaseous ozone on stainless steel. Tests were carried out by exposing inoculated tiles to gaseous ozone in a laboratorial chamber at concentrations up to 50 mg/L and at times up to 180 min (bacteria) or 300 min (filamentous fungi). For bacteria, the resistance to gaseous ozone of L. monocytogenes proved markedly higher than that of S. enterica. Their D‐values increased by seven times (from 27.3 to 200.7 min for the strain of L. monocytogenes studied; from 7.3 to 48.0 min for the Salmonella species studied) when the ozone concentration were reduced from 12 to 4 mg/L. For filamentous fungi, a substantial effect was observed only at 50 mg/L on single‐layered inocula: at these conditions, A. brasiliensis ATCC 16404 proved the most resistant strain to gaseous ozone, its D‐value (134.4 min) being higher than those registered for the tested strains of H. burtonii (9.9 min) and P. nordicum (17.1 min). The results demonstrated that the use of gaseous ozone as a sanitizing agent for environments and working surfaces seems to be a potential alternative to chemical sanitizers against the two pathogens studied, whereas it seemed effective against the three filamentous fungi studied only in limited circumstances. [ABSTRACT FROM AUTHOR]

We previously reported that patients with multidrug‐resistant tuberculosis (MDR‐TB) showed low systemic and Mtb‐induced Th22 responses associated to high sputum bacillary load and severe lung lesions suggesting that Th22 response could influence the ability of these patients to control bacillary growth and tissue damage. In MDR‐TB patients, the percentage of IL‐22+ cells inversely correlates with the proportion of senescent PD‐1+ T cells. Herein, we aimed to evaluate the pathways involved on the regulation of systemic and Mtb‐induced Th22 response in MDR‐TB and fully drug‐susceptible TB patients (S‐TB) and healthy donors. Our results show that while IL‐1β and IL‐23 promote Mtb‐induced IL‐22 secretion and expansion of IL‐22+ cells, TGF‐β inhibits this response. Systemic and in vitro Mtb‐induced Th22 response inversely correlates with TGF‐β amounts in plasma and in PBMC cultures respectively. The number of circulating PD‐1+ T cells directly correlates with plasmatic TGF‐β levels and blockade of PD‐1/PD‐L1 signalling enhances in vitro Mtb‐induced expansion of IL‐22+ cells. Thus, TGF‐β could also inhibit Th22 response through upregulation of PD‐1 expression in T cells. Higher percentage of IL‐23+ monocytes was observed in TB patients. In contrast, the proportion of IL‐1β+ monocytes was lower in TB patients with bilateral lung cavities (BCC) compared to those patients with unilateral cavities (UCC). Interestingly, TB patients with BCC showed higher plasmatic and Mtb‐induced TGF‐β secretion than patients with UCC. Thus, high TGF‐β secretion and subtle differences in IL‐23 and IL‐1β expression could diminish systemic and in vitro Mtb‐induced Th22 response along disease progression in TB patients. [ABSTRACT FROM AUTHOR]

The editorial discusses the trade-offs involved in determining the positivity threshold for faecal immunochemical tests (FIT) used in colorectal cancer (CRC) screening. A study of 47,265 Norwegians examined the impact of different positivity thresholds on colonoscopy demand, detection rates of CRC, advanced adenomas, and adverse events. The findings suggest that as the threshold increases, positivity rates decrease, while PPVs for CRC and AAs increase, but not for ASLs. The study highlights the need for countries and healthcare systems to optimize colonoscopy resources based on FIT thresholds, although the results may not be generalizable to other populations or FIT brands. [Extracted from the article]

Background: Standardized patient‐specific pretreatment dosimetry planning is mandatory in the modern era of nuclear molecular radiotherapy, which may eventually lead to improvements in the final therapeutic outcome. Only a comprehensive definition of a dosage therapeutic window encompassing the range of absorbed doses, that is, helpful without being detrimental can lead to therapy individualization and improved outcomes. As a result, setting absorbed dose safety limits for organs at risk (OARs) requires knowledge of the absorbed dose–effect relationship. Data sets of consistent and reliable inter‐center dosimetry findings are required to characterize this relationship. Purpose: We developed and standardized a new pretreatment planning model consisting of a predictive dosimetry procedure for OARs in patients with neuroendocrine tumors (NETs) treated with 177Lu‐DOTATATE (Lutathera). In the retrospective study described herein, we used machine learning (ML) regression algorithms to predict absorbed doses in OARs by exploiting a combination of radiomic and dosiomic features extracted from patients' imaging data. Methods: Pretreatment and posttreatment data for 20 patients with NETs treated with 177Lu‐DOTATATE were collected from two clinical centers. A total of 3412 radiomic and dosiomic features were extracted from the patients' computed tomography (CT) scans and dose maps, respectively. All dose maps were generated using Monte Carlo simulations. An ML regression model was designed based on ML algorithms for predicting the absorbed dose in every OAR (liver, left kidney, right kidney, and spleen) before and after the therapy and between each therapy session, thus predicting any possible radiotoxic effects. Results: We evaluated nine ML regression algorithms. Our predictive model achieved a mean absolute dose error (MAE, in Gy) of 0.61 for the liver, 1.58 for the spleen, 1.30 for the left kidney, and 1.35 for the right kidney between pretherapy 68Ga‐DOTATOC positron emission tomography (PET)/CT and posttherapy 177Lu‐DOTATATE single photon emission (SPECT)/CT scans. Τhe best predictive performance observed was based on the gradient boost for the liver, the left kidney and the right kidney, and on the extra tree regressor for the spleen. Evaluation of the model's performance according to its ability to predict the absorbed dose in each OAR in every possible combination of pretherapy 68Ga‐DOTATOC PET/CT and any posttherapy 177Lu‐DOTATATE treatment cycle SPECT/CT scans as well as any 177Lu‐DOTATATE SPECT/CT treatment cycle and the consequent 177Lu‐DOTATATE SPECT/CT treatment cycle revealed mean absorbed dose differences ranges from −0.55 to 0.68 Gy. Incorporating radiodosiomics features from the 68Ga‐DOTATOC PET/CT and first 177Lu‐DOTATATE SPECT/CT treatment cycle scans further improved the precision and minimized the standard deviation of the predictions in nine out of 12 instances. An average improvement of 57.34% was observed (range: 17.53%–96.12%). However, it's important to note that in three instances (i.e., Ga,C.1 → C3 in spleen and left kidney, and Ga,C.1 → C2 in right kidney) we did not observe an improvement (absolute differences of 0.17, 0.08, and 0.05 Gy, respectively). Wavelet‐based features proved to have high correlated predictive value, whereas non‐linear‐based ML regression algorithms proved to be more capable than the linear‐based of producing precise prediction in our case. Conclusions: The combination of radiomics and dosiomics has potential utility for personalized molecular radiotherapy (PMR) response evaluation and OAR dose prediction. These radiodosiomic features can potentially provide information on any possible disease recurrence and may be highly useful in clinical decision‐making, especially regarding dose escalation issues. [ABSTRACT FROM AUTHOR]

We are interested in providing an efficient numerical scheme to represent wave propagation in time domain for configurations where a fluid domain and a solid domain are separated by a thin coating layer. Various computational challenges and bottlenecks occur in this context: incorporating fluid–solid coupling, enabling non‐conform space discretization when wavelengths greatly differ from the fluid and the solid domain, and rendering robust time discretization w.r.t. the thin layer thickness. In order to address these issues, the proposed approach combines the mortar element method with so‐called effective transmission conditions, where the effect of the coating layer is incorporated through spring—mass coefficients at the interface between the fluid and solid domain. Using discrete energy arguments, we are able to prove that the associated fully discrete scheme is stable upon a stability condition independent of the thin coating layer. Moreover, we provide an efficient time marching algorithm leading to significantly improved performances, illustrated in 2D and 3D configurations linked to ultrasonic testing experiments modeling. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study is to scrutinize whether psychopathology symptom networks differ between those with and without lifetime: treatment seeking, treatment and treatment of longer duration. Methods: We created non‐exclusive groups of subjects with versus without lifetime treatment seeking, treatment and treatment of mid‐long‐term duration. We estimated Ising models and carried out network comparison tests (NCTs) to compare (a) overall connectivity and (b) network structure. Furthermore, we examined node strength. We used propensity score matching (PSM) to minimize potential confounding by indication for service use. Results: Based on data from 9,172 participants, there were no statistically significant differences in overall connectivity and network structure in those with versus without lifetime: treatment seeking (p =.75 and p =.82, respectively), treatment (p =.63 and p =.49, respectively) and treatment of mid‐longterm duration (p =.15 and p =.62, respectively). Notably, comparing networks with versus without service use consistently revealed higher node strength in 'obsessions' and 'aggression' and lower node strength in 'elevated mood' in all networks with service use. Conclusions: Findings suggest that after adjusting for potential confounding by indication for service use, there was no indication of an association in overall connectivity or network structure for lifetime treatment seeking, treatment and treatment of longer duration. However, selected structurally important symptoms differed consistently in all three comparisons. Our findings highlight the potential of network analysis methods to examine treatment mechanisms and outcomes. Specifically, more granular network characteristics on the node level may complement and enrich traditional outcomes in clinical research. [ABSTRACT FROM AUTHOR]

Introduction: Despite the increasing use of 18F‐fluorocholine (18F‐FCH) positron emission tomography (PET) in patients with prostate cancer, the acquisition protocol remains debated. We have evaluated the influence of the pelvic dynamic phase on the final reading of whole‐body 18F‐FCH PET, to assess the need for a two‐stage protocol. Reading the physician's experience and patient's previous treatment profile was also considered as potential influencing factors on final PET interpretation. Methods: All 18F‐FCH PET/CT performed from January 2018 to September 2019 in patients with prostate cancer and including a pelvic dynamic phase followed by a delayed whole‐body acquisition were retrospectively retrieved. PET/CT were analysed by one expert nuclear medicine physician and one resident. The whole‐body scan was analysed blinded (first reading) and nonblinded from the results of the dynamic phase. Results: 221 consecutive PET/CT were selected from 201 patients previously treated by radical prostatectomy (n = 31), pelvic radiation therapy (n = 60), or both (n = 94). 24 patients had no previous treatments, and 12 benefited from other focal treatments. In the whole population, dynamic acquisition modified final interpretation of 32/221 scans (14.5%) for residents, 26 (11.8%) for experts and 19 (8.6%) for consensual reading. No influence of previous treatments was found. The availability of a dynamic phase would have been responsible for treatment modification in 5/221 scans (2.3%). Considering only the prostate bed, dynamic acquisition modified the final interpretation in 7/125 (5.6%) studies (consensual reading) from patients with previous prostatic surgery and 4/84 (4.8%) scans from patients without a history of prostatic surgical intervention. No significant influence of dynamic acquisition was found on the final PET interpretation on prostate lodge accordingly to previous prostatic surgery. Conclusion: The dynamic phase changes the interpretation of 18F‐FCH PET in about 9% of cases and the therapeutic strategy in <3% of patients. The influence of the early phase reduces with physician experience. Patient's treatment profile does not appear to have a significant influence on the variability of interpretation, also including the prostate bed. [ABSTRACT FROM AUTHOR]

(2B) Reangulated 99mTc-tetrofosmin single photon emission computed tomography (SPECT/CT) rest perfusion images (short, vertical and horizontal axis) signifies a large perfusion deficit involving the inferolateral wall with mild extension inferiorly and apically associated with corresponding abnormal 18F-FDG uptake on PET/CT images. Cardiac sarcoidosis activity is commonly seen in the basal segments of the septum or lateral wall but may affect also any other myocardial segments like in inflammatory cardiomyopathy,9,10 while normal perfusion and no abnormal SP 18 sp F-FDG reliably rules out cardiac sarcoid disease. Notably, reduced regional perfusion correlating with an abnormal SP 18 sp F-FDG uptake indicates a "mismatch" between a focal decrease in myocardial perfusion and abnormal SP 18 sp F-FDG uptake (inflammation) (Figure 2). [Extracted from the article]

Introduction: The identification of dementia cases through routinely collected health data represents an easily accessible and inexpensive method to estimate the prevalence of dementia. In Italy, a project aimed at the validation of an algorithm was conducted. Methods: The project included cases (patients with dementia or mild cognitive impairment [MCI]) recruited in centers for cognitive disorders and dementias and controls recruited in outpatient units of geriatrics and neurology. The algorithm based on pharmaceutical prescriptions, hospital discharge records, residential long-term care records, and information on exemption from health-care co-payment, was applied to the validation population. Results: The main analysis was conducted on 1110 cases and 1114 controls. The sensitivity, specificity, and positive and negative predictive values in discerning cases of dementia were 74.5%, 96.0%, 94.9%, and 79.1%, respectively, whereas in detecting cases of MCI these values were 29.7%, 97.5%, 92.2%, and 58.1%, respectively. The variables associated with misclassification of cases were also identified. Discussion: This study provided a validated algorithm, based on administrative data, which can be used to identify caseswith dementia and, with lower sensitivity, also early onset dementia but not cases withMCI. [ABSTRACT FROM AUTHOR]

Crises and disasters are windows of opportunity to learn and transform toward enhancing disaster risk reduction (DRR) and resilience. However, a poor understanding of community resilience and the social dimensions of risk, the lack of a methodology to engage and empower resilience in society, and business‐as‐usual together limit the implementation of effective DRR and resilience‐building strategies. In this reflection paper, we discuss the main elements of the DRR and resilience paradigm. By analyzing the failures in disaster management, we identified the cultural and political barriers to enhancing DRR and community resilience as being: a paternalistic social protection culture; and the command‐and‐control approach to knowledge and resources for risk reduction. We reflect on the implications of this for sustainable development and argue that building a glocal culture of community wellbeing and resilience and a socially sustainable risk governance is needed to overcome the cultural and political barriers to DRR and sustainable development. [ABSTRACT FROM AUTHOR]

This paper reflects on what materialised during recovery operations following the earthquake in L'Aquila, Italy, on 6 April 2009. Previous critiques have focused on the actions of the Government of Italy and the Department of Civil Protection (Protezione Civile), with little attention paid to the role of local authorities. This analysis sheds light on how the latter used emergency powers, the command‐and‐control approach, and top‐down planning to manage the disaster context, especially in terms of removal of rubble, implementing safety measures, and allocating temporary accommodation. It discusses how these arrangements constituted the mechanism via which 'disaster capitalism' took hold at the local and national level, and how it violated human rights, produced environmental and social impacts, hindered local communities from learning, transforming, and building resilience, and facilitated disaster capitalism and corruption. To make the disaster risk reduction and resilience paradigm more effective, a shift from centralised civil protection to decentralised, inclusive community empowerment systems is needed. [ABSTRACT FROM AUTHOR]

The evaluation of new therapeutic resources against coronavirus disease 2019 (COVID‐19) represents a priority in clinical research considering the minimal options currently available. To evaluate the adjuvant use of systemic oxygen‐ozone administration in the early control of disease progression in patients with COVID‐19 pneumonia. PROBIOZOVID is an ongoing, interventional, randomized, prospective, and double‐arm trial enrolling patient with COVID‐19 pneumonia. From a total of 85 patients screened, 28 were recruited. Patients were randomly divided into ozone‐autohemotherapy group (14) and control group (14). The procedure consisted in a daily double‐treatment with systemic Oxygen–ozone administration for 7 days. All patients were treated with ad interim best available therapy. The primary outcome was delta in the number of patients requiring orotracheal‐intubation despite treatment. Secondary outcome was the difference of mortality between the two groups. Moreover, hematological parameters were compared before and after treatment. No differences in the characteristics between groups were observed at baseline. As a preliminary report we have observed that one patient for each group needed intubation and was transferred to ITU. No deaths were observed at 7–14 days of follow up. Thirty‐day mortality was 8.3% for ozone group and 10% for controls. Ozone therapy did not significantly influence inflammation markers, hematology profile, and lymphocyte subpopulations of patients treated. Ozone therapy had an impact on the need for the ventilatory support, although did not reach statistical significance. Finally, no adverse events related to the use of ozone‐autohemotherapy were reported. Preliminary results, although not showing statistically significant benefits of ozone on COVID‐19, did not report any toxicity. [ABSTRACT FROM AUTHOR]

The aim of the present study was to in vitro evaluate the effect of dentin conditioning with hydroabrasion on the microtensile bond strengths of three adhesive systems, compared to the standard etch-and-rinse technique. Sixty extracted human third molars were collected, and their midcoronal occlusal dentin was used for the microtensile bond strength test. Teeth were randomly assigned to three groups according to the adhesive system used: ExciTE F DSC, ENA Bond, and Scotchbond Universal. Specimens from each group were further divided into four subgroups: control specimens were treated with standard adhesive procedures; hydroabraded (HA) specimens were subjected to preventive hydroabrasion with three different intensity levels. After bonding procedures, composite crowns were incrementally built up. After thermocycling, specimens were subsequently sectioned into 1 × 1 mm sticks, and microtensile bond strengths were measured. Data were statistically analyzed. Failure mode analysis was performed. There were no significant differences in terms of bond strength between standard adhesion protocols and adhesion with HA preconditionings. On the other hand, the type of adhesive used had a significant effect on the tensile bond strength. Subgroups treated with hydroabrasion at higher intensity showed a slightly increased frequency of cohesive fractures. In conclusion, hydroabrasion can be used for dentin cavity preparation or finishing, since it does not seem to affect the bonding effectiveness. [ABSTRACT FROM AUTHOR]

Introduction: In patients with ileal neuroendocrine tumours (ileal NETs), head‐to‐head evaluation of diagnostic performances of 68Ga‐DOTA‐peptides and 18F‐fluorodihydroxyphenylalanine (18F‐FDOPA) positron emission tomography/computed tomography (PET/CT) has been performed in only few small patients' cohorts. The aim of this retrospective study was to compare 68Ga‐DOTATOC and 18F‐FDOPA PET/CT for metastatic disease assessment in a homogeneous large series of patients with well‐differentiated ileal NETs. Methods: All patients with ileal NETs who underwent both 18F‐FDOPA and 68Ga‐DOTATOC PET/CT within a 3‐month period and no therapeutic change between the two studies were retrospectively included. The detection rates of both modalities were calculated using per‐patient, per‐region and per‐lesion analyses. Results: Forty one patients with ileal NETs were evaluated. 18F‐FDOPA and 68Ga‐DOTATOC showed similar detection rates according to per‐patient (97% for both) and per‐region analyses (94% for 18F‐FDOPA vs 88% for 68Ga‐DOTATOC, P =.35). For a total of 605 positive lesions, 458 (76%) were detected by both modalities, 122 (20%) exclusively by 18F‐FDOPA PET/CT, and 25 (4%) by 68Ga‐DOTATOC PET/CT only. In a per‐lesion analysis, 18F‐FDOPA PET/CT performed better than 68Ga‐DOTATOC PET/CT (overall detection rates of 96% vs 80%; P <.001). 18F‐FDOPA PET/CT detected significantly more metastases than 68Ga‐DOTATOC PET/CT in the liver, peritoneum, abdominal and supra‐diaphragmatic lymph nodes. Conclusion: 18F‐FDOPA PET/CT seems not inferior than 68Ga‐DOTATOC PET/CT for the delineation of metastatic spread of ileal NETs. Therefore, according to local expertise and technical availability, 18F‐FDOPA should be considered as a valid clinical diagnostic option for exhaustive metastatic assessment in patients with ileal NETs. Obviously, 68Ga‐DOTATOC PET/CT remains mandatory for PRRT assessment. Further comparative studies are needed to determine the optimal approach in various clinical scenarios such as preoperative staging and primary tumour detection. [ABSTRACT FROM AUTHOR]

Few reports described the outcome of kidney transplanted patients (KTs) affected by COVID‐19 treated with interleukin‐6 receptor inhibitor tocilizumab (TCZ). We report our case series of 6 KTs with COVID‐19 pneumonia who received TCZ: All were of male gender, with a mean age of 55.5 ± 8.4 years, a median time from transplantation of 3611 days (1465‐5757); 5/6 had cardiovascular comorbidities, 1/6 had diabetes, and 3/6 have one or more previous KTs. Four out of six patients died, at an average time of 9.75 ± 2.4 days after tocilizumab administration, 3/6 due to a coexistent septic shock. Two patients improved after TCZ and were discharged at 20 and 21 days, respectively; in both patient, a significant increase of total lymphocyte count was observed. In conclusion, KTs, where the role of peculiar factors such as chronic immunosuppression is still undetermined, represent a high‐risk group with significant COVID‐19‐associated mortality. The evaluation of the TCZ effect in COVID‐19 pneumonia requires controlled studies (ideally RCTs) in this specific population. [ABSTRACT FROM AUTHOR]

Summary: Composite laminate structures remain an important family of materials used in cutting‐edge industrial areas. Building efficient numerical modeling tools for high‐frequency wave propagation in order to represent ultrasonic testing experiments of these materials remains a major challenge. In particular, incorporating attenuation phenomena within anisotropic plies, and thin intermediate isotropic layers between the plies often represent significant obstacles for standard numerical approaches. In our work, we address both issues by proposing a systematic study of the fully discrete propagators associated to the Kelvin‐Voigt, Maxwell, and Zener models, and by incorporating effective transmission conditions between plies using the mortar element method. We illustrate the soundness of our approach by proposing intermediate one‐dimensional and two‐dimensional numerical evidence, and we apply it to a more realistic configuration of a curved laminate composite structure in a three‐dimensional setting. [ABSTRACT FROM AUTHOR]

Background: This study evaluated the short- and long-term outcomes of synchronous resection of liver metastases (LM) from small bowel neuroendocrine tumors (SB-NET). Methods: A retrospective review of patients undergoing resection for LMs from SB-NETs from January 1997 and December 2018 was performed. Results: There were 44 patients with synchronous SB-NET and LMs. Perioperative and 90-day mortality values were zero, and the morbidity rate was 27%. The median overall survival (OS) was 128.4 months (CI 95% 74.0–161.5 months) with 1-, 3-, 5-, and 10-year survival rates of 100%, 83%, 79%, and 60%, respectively. Not achieving surgical treatment for LM was the unique independent factor for survival (HR 6.50; CI 95% 1.54–27.28; p = 0.01) in patients with unresected LMs having OS and 10-year survival rates (42 months, 33%) versus patients undergoing liver resection (152 months, 66%)(p = 0.0008). The recurrence rate was 81.8% and associated with longer OS and 5-year survival rates when limited to the liver [223 months (61%) vs 94 months (87%)]. Conclusions: Simultaneous resection of SB-NETs with synchronous LMs was safe and associated with considerable long-term survival even in the presence of bilobar disease. However, recurrence after resection was common (81%) but associated with longer survival rates when limited to the liver. [ABSTRACT FROM AUTHOR]

Objective: To assess the specificity of increased 18F‐dihydroxyphenylalanine (18F‐FDOPA) uptake in patients who underwent PET/CT for suspicion of isolated pancreatic neuroendocrine tumour (pNET). False‐positive results mimicking a pNET have been investigated. Material and methods: Carbidopa‐assisted 18F‐FDOPA PET/CT scans performed in patients with suspicion of localized pNET were retrieved. Only patients with a definitive diagnosis were retrospectively included. When available, the histopathological result after pancreatic surgery was the gold standard. In other cases, the diagnosis was based on endoscopic ultrasonography (EUS)/cytology and/or on concordant imaging results of at least two of the following: contrast‐enhanced computed tomography (CE‐CT), magnetic resonance imaging (MRI) and somatostatin receptor scintigraphy (SRS). Results: Forty‐four among 731 patients were selected. Among these, 36 patients (82%) were surgically treated, revealing pNET (n = 28), solid pseudopapillary tumour (SPT) (n = 4), adenocarcinoma (n = 2), serous cystadenomas (n = 1) and solitary fibrous tumour (n = 1) cases. An additional three cases of pNET were diagnosed by EUS/cytology. In the remaining five patients, a consensus was reached on follow‐up imaging results: pNET (n = 1), serous cystadenoma (n = 2) and undetermined/no pNET (n = 2). Both specificity and negative predictive value of 18F‐FDOPA PET/CT for localized pNET were 67%. Surprisingly, all four false‐positive results were SPTs showing intense 18F‐FDOPA uptake and negative SRS. There was no significant difference in 18F‐FDOPA uptake intensity between PET‐positive pNETs and SPTs. Conclusion: 18F‐FDOPA PET/CT is not specific for pNET in patients with localized pancreatic lesions. SPT could mimic pNET and should be part of differential diagnosis in such a clinical situation. If these results are confirmed in a broader population, the imaging pattern 18F‐FDOPA PET‐positive/SRS‐negative lesions might be considered as the imaging phenotype of SPT. [ABSTRACT FROM AUTHOR]

Summary: Proposing efficient numerical modeling tools for high‐frequency wave propagation in realistic configurations, such as the one appearing in ultrasonic testing experiments, is a major challenge, especially in the perspective of inversion loops or parametric studies. We propose a numerical methodology addressing this challenge and based upon the combination of the spectral finite element method and the mortar element method. From a prior decomposition of the scene of interest into "macro‐elements," we show how one can improve the performances of the standard finite element procedures in terms of memory footprint and computational load. Additionally, using this decomposition, we are able to efficiently reconstruct important modeling features on‐the‐fly, such as orientations of anisotropic materials or splitting directions of perfectly matched layers formulations, altogether in a robust and efficient manner. We believe that this strategy is particularly suitable for parametric studies and sensitivity analysis. We illustrate our strategy by simulating the propagation of an ultrasonic wave into an immersed and curved anisotropic laminate 3D specimen flawed with an internal circular delamination of varying size, thus showing the efficiency and the robustness of our approach. [ABSTRACT FROM AUTHOR]

Objective: Comprehensively describe the phenotypic spectrum of sporadic fatal insomnia (sFI) to facilitate diagnosis and management of this rare and peculiar prion disorder.Methods: A survey among major prion disease reference centers in Europe identified 13 patients diagnosed with sFI in the past 20 years. We undertook a detailed analysis of clinical and histopathological features and the results of diagnostic investigations.Results: Mean age at onset was 43 years, and mean disease duration 30 months. Early clinical findings included psychiatric, sleep, and oculomotor disturbances, followed by cognitive decline and postural instability. In all tested patients, video-polysomnography demonstrated a severe reduction of total sleep time and/or a disorganized sleep. Cerebrospinal fluid (CSF) levels of proteins 14-3-3 and t-tau were unrevealing, the concentration of neurofilament light protein (NfL) was more consistently increased, and the real-time quaking-induced conversion assay (RT-QuIC) revealed a positive prion seeding activity in 60% of cases. Electroencephalography and magnetic resonance imaging showed nonspecific findings, whereas fluorodeoxyglucose positron emission tomography (FDG-PET) demonstrated a profound bilateral thalamic hypometabolism in 71% of cases. Molecular analyses revealed PrPSc type 2 and methionine homozygosity at PRNP codon 129 in all cases.Interpretation: sFI is a disease of young or middle-aged adults, which is difficult to reconcile with the hypothesis of a spontaneous etiology related to stochastic, age-related PrP misfolding. The combination of psychiatric and/or sleep-related symptoms with oculomotor abnormalities represents an early peculiar clinical feature of sFI to be valued in the differential diagnosis. Video-polysomnography, FDG-PET, and especially CSF prion RT-QuIC and NfL constitute the most promising supportive diagnostic tests in vivo. Ann Neurol 2018;84:347-360. [ABSTRACT FROM AUTHOR]

Abstract: Octavius®‐4D is a very effective device in radiotherapy treatment quality assurance (QA), due to its simple set‐up and analysis package. However, even if it is widely used, its main characteristics and criticalities were only partially investigated. Taking start from its commissioning, the aim of this work was to study the main dependencies of the device response. The outcome dependence was studied comparing results by different delivery techniques [Intensity Modulated Radiation Therapy, IMRT (n = 29) and RapidArc, RA (n = 15)], anatomical regions [15 head/neck, 19 pelvis and 10 pancreas] and linear accelerators [DHX (n = 14) and Trilogy (n = 30)]. Moreover, the agreement dependency on the section of the phantom was assessed. Plan evaluations obtained by 2D, 3D, and volumetric γ‐index (both local and global) were also compared. Generally, high dose gradient resulted critically managed by the assembly, with a smoother effect in RA technique. Worse agreements emerged in the 2D γ‐index vs those of 3D and volumetric (P < 0.001), that were instead statistically comparable in global metric (P > 0.300). Volumetric plan evaluation was coherent with the average of passing rates on the 3 phantom axes (r ≥ 0.9), but transversal section provided best agreements vs sagittal and coronal ones (P < 0.050). The three studied districts furnished comparable results (P > 0.050) while the two LINACs provided different agreements (P < 0.005). The study pointed out that the phantom transversal section better fits the planned dose distribution, so this should be accounted when a two‐dimensional evaluation is needed. Moreover, the major reliability of the 3D metric with respect to the 2D one, as it better agrees with the dosimetric evaluation on the whole volume, suggests that it should be preferred in a two‐dimensional evaluation. Better agreements, obtained with RA vs IMRT technique, confirm that Octavius®‐4D is specifically conceived for rotational delivery. Lastly, the assembly resulted sensitive to different technology. [ABSTRACT FROM AUTHOR]

Objectives: Considering the similarities between HIV‐associated neurocognitive disorders (HAND) and neurodegenerative dementias and the frequency of executive dysfunctions among HIV‐positive patients, we evaluated the accuracy of the Frontal Assessment Battery and Clock‐Drawing Test together with the Three Questions Test and International HIV Dementia Scale to screen for HAND. Methods: A cross‐sectional monocentric study was conducted from 2010 to 2017. The index tests were represented by the four screening tools; the reference standard was represented by a comprehensive neurocognitive battery used to investigate 10 cognitive domains. Patients were screened by a trained infectious diseases physician and those showing International HIV Dementia Scale scores ≤ 10 and/or complaining of neurocognitive symptoms were then evaluated by a trained neuropsychologist. Results: A total of 650 patients were screened and 281 received the full neurocognitive evaluation. HAND was diagnosed in 140 individuals. The sensitivity, specificity, correct classification rate and area under the receiver operating characteristic curve (AUROC) were, respectively, as follows: Frontal Assessment Battery, 40.7%, 95.1%, 68.3% and 0.81; International HIV Dementia Scale, 74.4%, 56.8%, 65.4% and 0.73; Clock‐Drawing Test, 30.9%, 73.4%, 53.8% and 0.56; and Three Questions Test, 37.3%, 54.1% and 45.7%. Raising the Frontal Assessment Battery's cut‐off to ≤ 16 improved its sensitivity, specificity and correct classification rate to 78.0%, 63.9% and 70.8%, respectively. Conclusions: We observed poor screening performances of the Three Questions and Clock‐Drawing Tests. While the International HIV Dementia Scale showed a poor specificity, the Frontal Assessment Battery showed the highest correct classification rate and a promising performance at different exploratory cut‐offs. [ABSTRACT FROM AUTHOR]

Monepantel (MNP) is a novel anthelmintic compound launched into the veterinary pharmaceutical market. MNP is not licenced for use in dairy animals due to the prolonged elimination of its metabolite monepantel sulphone (MNPSO2) into milk. The goal of this study was to evaluate the presence of potential in vivo drug‐drug interactions affecting the pattern of milk excretion after the coadministration of the anthelmintics MNP and oxfendazole (OFZ) to lactating dairy cows. The concentrations of both parent drugs and their metabolites were measured in plasma and milk samples by HPLC. MNPSO2 was the main metabolite recovered from plasma and milk after oral administration of MNP. A high distribution of MNPSO2 into milk was observed. The milk‐to‐plasma ratio (M/P ratio) for this metabolite was equal to 6.75. Conversely, the M/P ratio of OFZ was 1.26. Plasma concentration profiles of MNP and MNPSO2 were not modified in the presence of OFZ. The pattern of MNPSO2 excretion into milk was also unchanged in animals receiving MNP plus OFZ. The percentage of the total administered dose recovered from milk was 0.09 ± 0.04% (MNP) and 2.79 ± 1.54% (MNPSO2) after the administration of MNP alone and 0.06 ± 0.04% (MNP) and 2.34 ± 1.38% (MNPSO2) after the combined treatment. The presence of MNP did not alter the plasma and milk disposition kinetics of OFZ. The concentrations of the metabolite fenbendazole sulphone tended to be slightly higher in the coadministered group. Although from a pharmacodynamic point of view the coadministration of MNP and OFZ may be a useful tool, the presence of OFZ did not modify the in vivo pharmacokinetic behaviour of MNP and therefore did not result in reduced milk concentrations of MNPSO2. [ABSTRACT FROM AUTHOR]

Real-Time Quaking-Induced Conversion ( RT-Qu IC) testing of human cerebrospinal fluid ( CSF) is highly sensitive and specific in discriminating sporadic CJD patients from those without prion disease. Here, using CSF samples from 113 CJD and 64 non-prion disease patients, we provide the first direct and concurrent comparison of our improved RT-Qu IC assay to our previous assay, which is similar to those commonly used internationally for CJD diagnosis. This extended comparison demonstrated a ~21% increase in diagnostic sensitivity, a 2-day reduction in average detection time, and 100% specificity. [ABSTRACT FROM AUTHOR]

Purpose: To compare sonohysterosalpingography (sono-HSG) with foam instillation (HyFoSy) versus saline solution (HyCoSy) in the evaluation of tubal patency.Methods: We prospectively enrolled 37 infertile women, scheduled for laparoscopy. The women were randomized into two groups: HyFoSy (group I) and HyCoSy (group II). The patients of both groups underwent laparoscopy with dye test. We assessed the diagnostic performance (sensitivity, specificity, and overall accuracy) of HyFoSy and HyCoSy, compared with laparoscopy and dye test, in the assessment of tubal patency.Results: Sono-HSG findings in tubal patency assessment obtained in the HyFoSy group were concordant with laparoscopic results in 94.4% of cases, with a sensitivity of 87.5% and a specificity of 100%, whereas in the HyCoSy group, concordance occurred in only 57.8% of examinations, with a sensitivity of 50% and a specificity of 66.6%.Conclusions: HyFoSy allows a more accurate diagnosis of tubal patency compared with HyCoSy. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:67-71, 2017. [ABSTRACT FROM AUTHOR]

A family of fourth-order coupled implicit--explicit time schemes is presented as a special case of fourth-order coupled implicit schemes for linear wave equations. The domain of interest is decomposed into several regions where different fourth-order time discretizations are used, chosen among a family of implicit or explicit fourth-order schemes. The coupling is based on a Lagrangian formulation on the boundaries between the several non-conforming meshes of the regions. A global discrete energy is shown to be preserved and leads to global fourth-order consistency in time. Numerical results in 1D and 2D for the acoustic and elastodynamics equations illustrate the good behavior of the schemes and their potential for the simulation of realistic highly heterogeneous media or strongly refined geometries, for which using everywhere an explicit scheme can be extremely penalizing. Accuracy up to fourth order reduces the numerical dispersion inherent to implicit methods used with a large time step and makes this family of schemes attractive compared with second-order accurate methods. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Vuik et al papers. To view these articles, visit https://doi.org/10.1111/apt.16638 [ABSTRACT FROM AUTHOR]

Closantel ( CLS) is currently used in programs for the strategic control of gastrointestinal nematodes. CLS is extralabel used in different dairy goat production systems. From available data in dairy cows, it can be concluded that residues of CLS persist in milk. The current work evaluated the concentration profiles of CLS in plasma and milk from lactating orally treated dairy goats to assess the residues pattern in dairy products such as cheese and ricotta. Six (6) female Saanen dairy goats were treated orally with CLS administered at 10 mg/kg. Blood and milk samples were collected between 0 and 36 days post-treatment. The whole milk production was collected at 1, 4, 7, and 10 days post-treatment to produce soft cheese and ricotta. CLS concentrations in plasma, milk, cheese, whey, and ricotta were determined by HPLC. The concentrations of CLS measured in plasma were higher than those measured in milk at all sampling times. However, the calculated withdrawal time for CLS in milk was between 39 and 43 days postadministration to dairy goats. CLS residual concentrations in cheese (between 0.93 and 1.8 μg/g) were higher than those measured in the milk used for its production. CLS concentrations in ricotta were sixfold higher than those in the milk and 20-fold higher than those in the whey used for its production. The persistent and high residual concentrations of CLS in the milk and in the cheese and ricotta should be seriously considered before issuing any recommendation on the extralabel use of CLS in dairy goat farms. [ABSTRACT FROM AUTHOR]

This special issue aims to help the scientific and policy communities overcome these constraints, and it contributes to social sciences, sustainability science, and the sustainable development discourse generally, by enhancing understanding of the knowledge production processes and governance strategies that are relevant to enhancing DRR and resilience and to achieving the Sustainable Development Goals in society. Integrating effective disaster risk reduction (DRR) and community resilience-building strategies into development policies, plans, programs and projects is now understood as being crucial to achieve the sustainable development goals (SDGs), especially in vulnerable and disaster-prone regions. [Extracted from the article]

The lprG-p55 operon of Mycobacterium tuberculosis and Mycobacterium bovis is involved in the transport of toxic compounds. P55 is an efflux pump that provides resistance to several drugs, while LprG is a lipoprotein that modulates the host's immune response against mycobacteria. The knockout mutation of this operon severely reduces the replication of both mycobacterial species during infection in mice and increases susceptibility to toxic compounds. In order to gain insight into the function of LprG in the Mycobacteriumavium complex, in this study, we assayed the effect of the deletion of lprGgene in the D4ER strainof Mycobacterium avium subsp. avium. The replacement of lprG gene with a hygromycin cassette caused a polar effect on the expression of p55. Also, a twofold decrease in ethidium bromide susceptibility was observed and the resistance to the antibiotics rifampicin, amikacin, linezolid, and rifabutin was impaired in the mutant strain. In addition, the mutation decreased the virulence of the bacteria in macrophages in vitro and in a mice model in vivo. These findings clearly indicate that functional LprG and P55 are necessary for the correct transport of toxic compounds and for the survival of MAA in vitro and in vivo. [ABSTRACT FROM AUTHOR]

SUMMARY This paper presents an original approach to design perfectly matched layers for anisotropic scalar wave equations. This approach is based, first, on the introduction of a modified wave equation and, second, on the formulation of general 'perfectly matched' transmission conditions for this equation. The stability of the transmission problem is discussed by way of the adaptation of a high frequency stability (necessary) condition, and we apply our approach to construct perfectly matched layer suited for any convex domain with straight boundaries. A new variational formulation of the problem, including a Lagrange multiplier at the interface between the physical and the absorbing domains, is then set, and numerical results are presented in 2D and 3D. These results show the efficiency of our approach when using constant damping coefficients combined with high order elements. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Characteristic cardiac valve abnormalities and left ventricular hypertrophy are present in untreated patients with mucopolysaccharidosis type VI (MPS VI). Cardiac ultrasound was performed to investigate these findings in subjects during long-term enzyme replacement therapy (ERT) with recombinant human arylsulfatase B (rhASB, rhN-acetylgalactosamine 4-sulfatase, galsulfase, Naglazyme®). Studies were conducted in 54 subjects before ERT was begun and at specific intervals for up to 96 weeks of weekly infusions of rhASB at 1 mg/kg during phase 1/2, phase 2, and phase 3 trials of rhASB. At baseline, mitral and aortic valve obstruction was present and was significantly greater in those ≥12 years of age. Mild mitral and trace aortic regurgitation were present, the former being significantly greater in those <12 years. Left ventricular hypertrophy, with averaged z-scores ranging from 1.6-1.9 SD greater than normal, was present for ages both <12 and ≥12 years. After 96 weeks of ERT, ventricular septal hypertrophy regressed in those <12 years. For those ≥12 years, septal hypertrophy was unchanged, and aortic regurgitation increased statistically but not physiologically. Obstructive gradients across mitral and aortic valves remained unchanged. The results suggest that long-term ERT is effective in reducing intraventricular septal hypertrophy and preventing progression of cardiac valve abnormalities when administered to those <12 years of age. [ABSTRACT FROM AUTHOR]

Background. Endarterectomy (CEA) or stenting (CAS) of a stenotic carotid artery is currently undertaken to reduce stroke risk. In addition removal of the arterial narrowing has been hypothesized to improve cerebral hemodynamics and provide benefits in cognitive functions, by supposedly resolving a "hypoperfusion" condition. Methods. In this study we sought to test whether resolution of a carotid stenosis is followed bymeasurable changes in cognitive functions in 22 subjects with "asymptomatic" stenosis. Results. A main finding of the study was the statistically significant pre-post difference observed in the performance of phonological verbal fluency and Rey's 15-word immediate recall. Remarkably, there was a significant interaction between phonological verbal fluency performance and side of the carotid intervention, as the improvement in the verbal performance, a typical "lateralized" skill, was associated with resolution of the left carotid stenosis. Conclusion.The results reflect a substantial equivalence of the overall performance at the before- and after- CEA or CAS tests. In two domains, however, the postintervention performance resulted improved.The findings support the hypothesis that recanalization of a stenotic carotid could improve brain functions by resolving hypothetical "hypoperfusion" states, associated with the narrowing of the vessels. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant chemoradiation (CRT) therapy may result in significant tumor regression in patients with rectal cancer. Patients who develop complete tumor regression have been managed by treatment strategies that are alternatives to standard total mesorectal excision. Therefore, assessment of tumor response with positron emission tomography/computed tomography (PET/CT) after neoadjuvant treatment may offer relevant information for the selection of patients to receive alternative treatment strategies. Methods: Patients with clinical T2 (cT2) through cT4NxM0 rectal adenocarcinoma were included prospectively. Neoadjuvant therapy consisted of 54 grays of radiation and 5-fluorouracil-based chemotherapy. Baseline PET/CT studies were obtained before CRT followed by PET/CT studies at 6 weeks and 12 weeks after the completion of CRT. Clinical assessment was performed at 12 weeks after CRT completion. PET/CT results were compared with clinical and pathologic data. Results: In total, 99 patients were included in the study. Twenty-three patients were complete responders (16 had a complete clinical response, and 7 had a complete pathologic response). The PET/CT response evaluation at 12 weeks indicated that 18 patients had a complete response, and 81 patients had an incomplete response. There were 5 false-negative and 10 false-positive PET/CT results. PET/CT for the detection of residual cancer had 93% sensitivity, 53% specificity, a 73% negative predictive value, an 87% positive predictive value, and 85% accuracy. Clinical assessment alone resulted in an accuracy of 91%. PET/CT information may have detected misdiagnoses made by clinical assessment alone, improving overall accuracy to 96%. Conclusions: Assessment of tumor response at 12 weeks after CRT completion with PET/CT imaging may provide a useful additional tool with good overall accuracy for the selection of patients who may avoid unnecessary radical resection after achieving a complete clinical response. Cancer 2012;3501-3511. © 2011 American Cancer Society. [ABSTRACT FROM AUTHOR]

Sallovitz, J. M., Nejamkin, P., Lifschitz, A. L., Virkel, G. L., Imperiale, F. A., Lanusse, C. E. Comparative in vitro characterization of moxidectin and doramectin percutaneous absorption through bovine skin. J. vet. Pharmacol. Therap. 35, 184-192. Topical formulations have achieved worldwide acceptance in veterinary medicine because their administration is an easy, less labor-intensive and nonstressing form. Any chemical compound that comes in contact with the skin has the potential to be locally and/or systemically absorbed. However, many factors related to the features of animal skin, composition of the topical formulation and to the drug itself can determine marked differences in the percutaneous absorption process. The aim of the current work was to characterize the pattern of in vitro percutaneous absorption for moxidectin (MXD) and doramectin (DRM), two of the most worldwide used topical macrocyclic lactone antiparasitic compounds in cattle. The work included the development of a simple and inexpensive in vitro assay useful to predict in vivo drug percutaneous absorption in cattle. Both drugs were administered as the commercial formulations intended for their topical administration to cattle. The in vitro studies were carried out using modified Franz-type vertical diffusion cells. Cattle skin slices of 500 μm thickness were prepared using a dermatome to separate the stratum corneum and upper epidermis from dermis and subcutaneous tissue. The receptor medium was sampled up to 72 h postadministration and drug concentrations were measured by HPLC. The parameters used to estimate the comparative in vitro skin permeation showed marked differences between DRM and MXD. A 5.29-fold longer lag time ( Tlag) was observed for DRM. Similarly, the flux ( J) (2.93-fold) and the permeation coefficients ( Kp) (2.95-fold) in cattle skin were significantly higher ( P < 0.05) for DRM compared to those obtained for MXD. Additionally, the data obtained from the in vitro permeation studies was correlated with the plasma concentrations of both compounds achieved in vivo in cattle treated with the same topical formulations. Correlation coefficients between percentage of drug permeated in vitro vs. percentage of drug absorbed in vivo (up to 48 h post-treatment) were 0.856-0.887 (MXD) and 0.976-0.990 (DRM). However, the highest in vitro-in vivo correlations for both molecules were observed up to 24 h post-treatment A rapid screening method for testing different topical formulations can be achieved with the simple in vitro cattle skin permeation technique described here, which has been successfully adapted to test the comparative percutaneous absorption of MXD and DRM. [ABSTRACT FROM AUTHOR]

Bovine tuberculosis is caused by Mycobacterium bovis, a mycobacterium highly similar to M. tuberculosis that belongs to the M. tuberculosis complex. The main host of M. bovis is cattle but it also affects many other mammalians including humans. Tuberculosis in humans caused by either M. bovis or M. tuberculosis is clinically hard to distinguish. During 2004–2005, samples from 448 patients with diagnosis of TB were collected from different regions of Argentina. The PRA technique identified 400 isolates with representative patterns of mycobacterium. The predominant ones were the M. tuberculosis complex, the M. avium– M. intracellulare complex and M. gordonae. Samples with M. tuberculosis complex PRA restriction profiles were analyzed with a multiplex PCR to differentiate between M. tuberculosis and M. bovis. Multiplex PCR identified nine M. bovis. The results allowed the possibility to establish that 2% of pulmonary tuberculosis was due to M. bovis. Isolates of M. bovis from humans were examined using spoligotyping. These isolates presented five different spoligotypes. The main spoligotype was also the most frequently one found in cattle. The remaining human spoligotypes (grouped in clusters) are occasionally found in cattle. Variable number tandem repeat (VNTR) analysis identified five different patterns. By combining the results of spoligotyping and VNTR analysis, we were able to differentiate seven M. bovis isolates. The remaining two M. bovis samples showed the same spoligotype and VNTR profile and belonged to household contacts. An MDR- M. bovis was isolated from the samples of these household contacts. The identification of two epidemiologically linked cases of human M. bovis infection suggests person-to-person transmission of an MDR- M. bovis. [ABSTRACT FROM AUTHOR]

Background: Although it has been recently demonstrated that there was no significant difference in total survival and clinical outcomes between patients who underwent coronary artery bypass grafting (CABG) with or without surgical ventricular reconstruction (SVR), the question of whether or not SVR decreases the arrhythmic risk profile in this population has not been clarified yet. Objective: To determine the real incidence of sudden cardiac death (SCD) and sustained ventricular tachycardia/ventricular fibrillation (sustained VT/VF) in patients following CABG added to SVR and to define their clinical and echocardiographic parameters predicting in-hospital and long-term arrhythmic events (SCD + sustained VT/VF). Methods: Pre- and postoperative clinical and echocardiographic values as well as postoperative electrocardiogram Holter data of 65 patients (21 female, 63 ± 11 years) who underwent SVR + CABG were retrospectively evaluated. Results: Mean follow-up was 1,105 ± 940 days. At 3 years, the SCD-free rate was 98% and the rate free from arrhythmic events was 88%. Multivariate logistic analysis identified a preoperative left ventricular end-systolic volume index (LVESVI) > 102 mL/m2 (odds ratio [OR] 1.4, confidence interval [CI] 1.073–1.864, P = 0.02; sensitivity 100%, specificity 94%) and a postoperative pulmonary artery systolic pressure (PASP) > 27 mmHg (OR 2.3, CI 1.887–4.487, P = 0.01; sensitivity 100%, specificity 71%) as independent predictors of arrhythmic events. Conclusions: Our and previous studies report a low incidence of arrhythmic events in patients following SVR added to CABG, considering the high-risk profile of the study population. A preoperative LVESVI > 102 mL/m2 and a postoperative PASP > 27 mmHg had a good sensitivity and specificity in predicting arrhythmic events. (PACE 2010; 33:1054–1062) [ABSTRACT FROM AUTHOR]

Aliment Pharmacol Ther 2010; 32: 171–181 Background Randomized controlled trials (RCTs) comparing polyethylene glycol (PEG) with sodium phosphate (NaP) are inconsistent. Aim To compare the efficacy of and tolerance to PEG vs. NaP for bowel preparation. Methods We used MEDLINE and EMBASE to identify English-language RCTs published between 1990 and 2008 comparing 4-L PEG with two 45 mL doses of NaP in adults undergoing elective colonoscopy. We calculated the pooled odds ratios (ORs) for preparation quality and proportion of subjects completing the preparation. Results From 18 trials ( n = 2792), subjects receiving NaP were more likely to have an excellent or good quality preparation than those receiving PEG (82% vs. 77%; OR = 1.43; 95% CI, 1.01–2.00). Among a subgroup of 10 trials in which prep quality was reported in greater detail, there were no differences in the proportions of excellent, good, fair or poor preparation quality. Among nine trials that assessed preparation completion rates, patients receiving NaP were more likely to complete the preparation than patients receiving 4-L PEG (3.9% vs. 9.8% respectively did not complete the preparation; OR = 0.40; CI, 0.17–0.88). Conclusion Among 18 head-to-head RCTs of NaP vs. 4-L PEG, NaP was more likely to be completed and to result in an excellent or good quality preparation. [ABSTRACT FROM AUTHOR]

Objective: The aim of our study was to evaluate the diagnostic contribution of 18F-fluoro-deoxyglucose (18F-FDG)-positron emission tomography (PET)/computed tomography (CT) in patients with fever of unknown origin (FUO) or unexplained prolonged inflammatory syndrome (UPIS) in real life. Patients and methods: We performed a retrospective study including 14 patients with FUO or UPIS hospitalised in our institution (Strasbourg University Hospital, France) between January 2005 and July 2006. 18F-FDG-PET/CT was considered helpful when abnormal results allowed an accurate diagnosis. Results: 18F-FDG-PET/CT was helpful in half the patients (7/14) for final diagnosis. A diagnosis was reached in 87.5% of the patients (7/8) with an abnormal 18F-FDG-PET/CT but only in 50% of the patients (3/6) with a normal 18F-FDG-PET/CT. Conventional chest and abdominal CT was performed in 13 patients before ordering 18F-FDG-PET/CT. We considered that 18F-FDG-PET/CT was essential to establish the final diagnosis in only 23% of the patients (3/13) since neither chest nor abdominal CT identified abnormalities consistent with the final diagnosis. However, among the three patients, two were diagnosed with large vessel vasculitis and one patient with local prosthetic infection. Conclusions: Our study supports the potential interest of 18F-FDG-PET/CT in the diagnostic workup of FUO and UPIS as it helped establish a fine diagnosis in half of the cases. However, 18F-FDG-PET/CT appeared to be essential to the final diagnosis in only 23% of the cases. In our opinion, this protocol should be performed as a second level test, especially when conventional CT is normal or is unable to discriminate between active and silent lesions. [ABSTRACT FROM AUTHOR]

A 56‐year‐old patient with a history of bilateral lung transplantation for idiopathic interstitial pneumonia not responding to corticosteroids therapy had a good initial postoperative outcome. One month later, subcutaneous nodules appeared and histopathology revealed septate hyphae in the nodules and Aspergillus fumigatus in bronchial lavage. FDG PET/CT and CMR revealed multiple left and right ventricles abscesses consistent with cardiac aspergillosis. The combination of FDG PET/CT and CMR was useful to detect the cardiac localization of systemic aspergillosis, to define the precise morphological details of myocardial lesions and to evaluate the response to treatment. [ABSTRACT FROM AUTHOR]

Pour-on administration of the macrocyclic lactones anti-parasitic compounds in beef and dairy cattle is now worldwide accepted. However, the information available on their milk excretion pattern, after topical administration is rather limited. Additionally, the cattle licking behaviour has been proven to affect the kinetics of these anti-parasitic compounds. The purpose of this study was to investigate the influence of the natural licking behaviour on the plasma and milk disposition of moxidectin (MXD), topically administered (500 μg/kg) in lactating dairy cows. Ten lactating Holstein dairy cows (705 kg body weight) were allocated into two experimental groups ( n = 5). The licking was prevented during 5 days postadministration in animals in group I, and the remaining cows (group II) were allowed to lick freely. MXD concentrations profiles were measured in plasma and milk over 15 days posttreatment. The licking restriction period caused marked changes in MXD disposition kinetics both in plasma and milk. Both plasma and milk MXD concentrations (partial AUC 0–5 days) were significantly lower ( P < 0.05) in licking-restricted cows. After the 5-day of restriction period, the animals were allowed to lick freely, which permitted the oral ingestion of MXD, situation clearly reflected both in plasma profile and milk excretion pattern. Despite the enhanced MXD milk concentrations measured in free-licking cows, drug concentrations did not reach the maximum MXD residues limit. [ABSTRACT FROM AUTHOR]

Ataxia is a frequently reported symptom in prion diseases (PD) and it is characteristic of Gerstmann-Sträussler-Scheinker syndrome (GSS), a genetic PD mainly related to the P102L mutation in the PRNP gene. Our aim was to screen for the P102L and other six known PRNP gene mutations (P105L, A117V, Y145X, E200K, D202N, and V210I) a group of 206 consecutive patients diagnosed with adult-onset cerebellar ataxia of unknown origin. The patients, negative for the most common acquired and genetic forms, were analyzed using a combination of restriction endonuclease digestion and pyrosequencing; eight, affected by ataxia and cognitive dysfunction, were also sequenced for the PRNP gene. One patient resulted to be heterozygous for the P102L mutation. Retrospectively, the clinical picture was consistent with a "classical" GSS phenotype. In conclusion, the screening for the P102L mutation, or even the sequencing of the PRNP gene should be taken in consideration in patients with late-onset ataxia (>50 years). [ABSTRACT FROM AUTHOR]

Aim of the study was to evaluate the role of atrial (ANP) and brain natriuretic peptides (BNP) as markers of preclinical cardiac disease in obesity. We selected 26 obese (BMI > 29 kg m−2) never-treated hypertensives (24-h BP > 140 and/or 90 mmHg), 26 obese normotensives (24-h BP < 130/80 mmHg) and 25 lean (BMI  25 kg m−2) never-treated hypertensives. Each subject underwent measurements of ANP and BNP plasma levels, 24-h ambulatory blood pressure (BP) monitoring, digitized M-mode and Doppler echocardiography. Mean values of ANP and BNP were similar among the three groups. All the subjects had normal left ventricular (LV) systolic function. Within each group ANP levels were higher in patients with LV diastolic dysfunction than in patients with normal diastolic function, and BNP levels were higher in patients with LV hypertrophy and in patients with LV diastolic dysfunction. Within each group, ANP levels were inversely correlated with LV diastolic indices, whereas BNP levels were directly correlated with LV mass index and inversely correlated with LV diastolic indices. ANP and BNP levels were not correlated with other echocardiographic parameters, age, BMI or 24-h BP values. In normotensive and hypertensive obese subjects the relationships of ANP and BNP levels with LV morpho-functional characteristics follow the same trend as in lean hypertensives, with ANP mainly influenced by diastolic dysfunction and BNP influenced by both LV hypertrophy and LV diastolic dysfunction. Therefore ANP and BNP can be considered useful markers of preclinical cardiac disease in obesity. Eur J Clin Invest 2004; 34 (5): 342–348 [ABSTRACT FROM AUTHOR]