BACKGROUND Interstitial lung disease (ILD) is the leading cause of morbidity and mortality in patients with systemic sclerosis (SSc); however, prognostication of SSc-associated ILD (SSc-ILD) remains ...challenging. We conducted a systematic review to identify variables that predict mortality and ILD progression in SSc-ILD. METHODS Three databases were searched to identify all studies relating to predictors of mortality or ILD progression in SSc-ILD. Studies were eligible if they were published in English and included ≥ 10 adults with SSc-ILD. Two authors independently reviewed and extracted data from acceptable studies. RESULTS The initial search identified 3,145 unique citations. Twenty-seven studies, including six abstracts, met the inclusion criteria. A total of 1,616 patients with SSc-ILD were included. Patient-specific, ILD-specific, and SSc-specific variables predicted mortality and progression; however, most predictors were identified in only one study. Most studies did not fully account for potential confounders, and none of the studies included a validation cohort. Older age, lower FVC, and lower diffusing capacity of carbon monoxide predicted mortality in more than one study. Male sex, extent of disease on high-resolution CT (HRCT) scan, presence of honeycombing, elevated KL-6 values, and increased alveolar epithelial permeability were identified as predictors of both mortality and ILD progression on unadjusted analysis. The extent of disease on HRCT scan was the only variable that independently predicted both mortality and ILD progression. CONCLUSIONS Mortality and ILD progression were predicted by several patient-specific, ILD-specific, and SSc-specific factors. Additional prospective studies are required to validate these preliminary findings and to identify combinations of variables that accurately predict the prognosis of SSc-ILD.
BAG-1 is an anti-apoptotic protein that is frequently deregulated in a variety of malignancies including colorectal cancer. There are three isoforms: BAG-1L is located in the nucleus, BAG-1M and ...BAG-1S are located both in the nucleus and the cytoplasm. In colon cancer, the expression of nuclear BAG-1 is associated with poorer prognosis and is potentially a useful predictive factor for distant metastasis. However, the function of BAG-1 in colonic epithelial cells has not been studied. Having previously shown a predominant nuclear localisation of BAG-1 in adenoma-derived cell lines, we wanted to determine the function of nuclear BAG-1 in these non-tumourigenic cells, to identify whether nuclear BAG-1 was implicated in tumour progression in the colon. In the current report we established that nuclear BAG-1 inhibits apoptosis in a colorectal adenoma-derived cell line. We demonstrate that apoptosis induced by gamma-radiation or the vitamin D analogue EB1089 in the non-tumourigenic human colorectal adenoma-derived S/RG/C2 cell line, was preceded by a decrease in nuclear and an increase in cytoplasmic BAG-1 expression. This change in subcellular localisation of BAG-1 was due to the redistribution of the BAG-1M isoform. In addition, we have shown that the maintenance of high nuclear BAG-1 through enforced expression of the nuclear localised BAG-1L isoform enhanced cellular survival after gamma-radiation or exposure to EB1089. Furthermore the expression of cytoplasmic BAG-1S isoform fused with a nuclear localisation signal protected against gamma-radiation induced apoptosis. This demonstrates that nuclear localisation of the BAG-1 protein confers a survival advantage in colorectal adenoma-derived cells and that nuclear BAG-1 could potentially be an important survival factor in colorectal carcinogenesis.
Positron beams, both polarized and unpolarized, are identified as essential ingredients for the experimental programs at the next generation of lepton accelerators. In the context of the hadronic ...physics program at Jefferson Lab (JLab), positron beams are complementary, even essential, tools for a precise understanding of the electromagnetic structure of nucleons and nuclei, in both the elastic and deep-inelastic regimes. For instance, elastic scattering of polarized and unpolarized electrons and positrons from the nucleon enables a model independent determination of its electromagnetic form factors. Also, the deeply-virtual scattering of polarized and unpolarized electrons and positrons allows unambiguous separation of the different contributions to the cross section of the lepto-production of photons and of lepton-pairs, enabling an accurate determination of the nucleons and nuclei generalized parton distributions, and providing an access to the gravitational form factors. Furthermore, positron beams offer the possibility of alternative tests of the Standard Model of particle physics through the search of a dark photon, the precise measurement of electroweak couplings, and the investigation of charged lepton flavor violation. This document discusses the perspectives of an experimental program with high duty-cycle positron beams at JLab.
Background Although coronary CT angiography (CTA) shows high diagnostic performance for detection and exclusion of obstructive coronary artery disease, limited temporal resolution of ...current-generation CT scanners may allow for motion artifacts, which may result in nonevaluable coronary segments. Objective We assessed a novel vendor-specific motion-correction algorithm for its effect on image quality and diagnostic accuracy. Methods Thirty-six consecutive patients with severe aortic stenosis undergoing coronary CTA without rate control and invasive coronary angiography as part of an evaluation for transcatheter aortic valve replacement. We compared image quality and diagnostic accuracy between standard (STD) and motion-corrected (MC) reconstructions. Coronary CTAs were interpreted in an intent-to-diagnose fashion by 2 experienced readers; a third reader provided consensus for interpretability and obstructive coronary stenosis (≥50% stenosis). All studies were interpreted with and without motion correction using both 45% and 75% of the R-R interval for reconstructions. Quantitative coronary angiography was performed by a core laboratory. Results Mean age was 83.0 ± 6.4 years; 47% were men. Overall image quality (graded 1–4) was higher with the use of MC versus STD reconstructions (2.9 ± 0.9 vs 2.4 ± 1.0; P < 0.001). MC reconstructions showed higher interpretability on a per-segment 97% (392/406) vs 88% (357/406); P < 0.001 and per-artery 96% (128/134) vs 84% (112/134); P = 0.002 basis, with no difference on a per-patient level 92% (33/36) vs 89% (32/36); P = 1.0. Diagnostic accuracy by MC reconstruction was higher than STD reconstruction on a per-segment 91% (370/406) vs 78% (317/406); P < 0.001 and per-artery level 86% (115/134) vs 72% (96/134); P = 0.007 basis, with no significant difference on a per-patient level 86% (31/36) vs 69% (25/36); P = 0.16. Conclusions The use of a novel MC algorithm improves image quality, interpretability, and diagnostic accuracy in persons undergoing coronary CTA without rate-control medications.
Abstract Background context Patients with sciatica frequently experience disabling back pain. One of the proposed causes for back pain is vertebral end-plate signal changes (VESC) as visualized by ...magnetic resonance imaging (MRI). Purpose To report on VESC findings, changes of VESC findings over time, and the correlation between VESC and disabling back pain in patients with sciatica. Study design/setting A randomized clinical trial with 1 year of follow-up. Patients sample Patients with 6 to 12 weeks of sciatica who participated in a multicenter, randomized clinical trial comparing an early surgery strategy with prolonged conservative care with surgery if needed. Outcome measures Patients were assessed by means of the 100-mm visual analog scale (VAS) for back pain (with 0 representing no pain and 100 the worst pain ever experienced) at baseline and 1 year. Disabling back pain was defined as a VAS score of at least 40 mm. Methods Patients underwent MRI both at baseline and after 1 year follow-up. Presence and change of VESC was correlated with disabling back pain using chi-square tests and logistic regression analysis. Results At baseline, 39% of patients had disabling back pain. Of the patients with VESC at baseline, 40% had disabling back pain compared with 38% of the patients with no VESC (p=.67). The prevalence of type 1 VESC increased from 1% at baseline to 35% 1 year later in the surgical group compared with an increase from 3% to 11% in the conservative group. The prevalence of type 2 VESC decreased from 40% to 29% in the surgical group while remaining almost stable in the conservative group at 41%. The prevalence of disabling back pain at 1 year was 12% in patients with no VESC at 1 year, 16% in patients with type 1 VESC, 11% in patients with type 2 VESC, and 3% in patients with both types 1 and 2 VESC (p=.36). Undergoing surgery was associated with increase in the extent of VESC (odds ratio OR, 8.6; 95% confidence interval CI, 4.7–15.7; p<.001). Patients who showed an increase in the extent of VESC after 1 year did not significantly report more disabling back pain compared with patients who did not show any increase (OR, 1.2; 95% CI, 0.6–2.6; p=.61). Conclusion In this study, undergoing surgery for sciatica was highly associated with the development of VESC after 1 year. However, in contrast with the intuitive feeling of spine specialists, those with and those without VESC reported disabling back pain in nearly the same proportion. Therefore, VESC does not seem to be responsible for disabling back pain in patients with sciatica.
Abstract Purpose To determine if there is a statistically significant difference in the computed tomography (CT)–guided trans-thoracic needle biopsy diagnostic rate, complication rate, and degree of ...pathologist confidence in diagnosis between core needle biopsy (CNB) and fine needle aspiration biopsy (FNAB). Methods A retrospective cohort design was used to compare the diagnostic biopsy rate, diagnostic confidence, and biopsy-related complications of pneumothorax, chest tube placement, pulmonary hemorrhage, hemoptysis, admission to hospital, and length of stay between 251 transthoracic needle biopsies obtained via CNB (126) or FNAB (125). Complication rates were assessed using imaging and clinical follow-up. Final diagnosis was confirmed via surgical pathology or clinical follow-up over a period of up to 10 years. Results CNB provided diagnostic samples in 91% and FNA in 80% of biopsies, which was statistically significant ( P < .05). The sensitivities for CNB and FNAB were 89% (85 of 95) and 95% (84 of 88), respectively. The specificity of CNB was 100% (21 of 21) and for FNAB was 81% (2 of 11) with 2 false positives in the FNAB group. The differences in complication rate was not statistically significant for pneumothorax (50% vs 46%; determined by routine postbiopsy CT), chest tube (2% vs 4%), hemoptysis (4% vs 6%), and pulmonary hemorrhage (38% vs 47%) between FNAB and CNB, respectively. Seven patients requiring chest tube were admitted to hospital, 2 in the FNAB cohort for an average of 2.5 days and 5 in the CNB cohort for an average of 4.6 days. Conclusions CNB provided more diagnostic samples with no statistical difference in complication rate.
With the evolution of additive techniques from prototyping tools (Rapid Prototyping; RP) to the production of actual end-use parts (Additive Manufacturing; AM), there is a growing need to develop and ...be able to process a much greater variety of materials than is currently possible. The handful of current polymeric materials that exist for processing by additive techniques does not meet the requirements of the majority of commercial products. There is therefore considerable interest from industrial and academic organisations, who realise the capabilities this technology has in the design and implementation of products, to increase material choice and to have a comprehensive understanding of the fundamental material properties. This review paper looks at the factors that need to be considered when selecting and processing polymers and the research that has been carried out to date, focussing on laser sintering, which is one of the most established and widely used Additive Manufacturing approaches. It also examines the limitations of current laser sintering systems in relation to the processing of polymer materials. The effect this has on the development of new and improved materials for laser sintering is evaluated, in addition to the difficulties experienced in maintaining consistency with current laser sintering polymers.
Three-dimensional lattices have applications across a range of fields including structural lightweighting, impact absorption and biomedicine. In this work, lattices based on triply periodic minimal ...surfaces were produced by polymer additive manufacturing and examined with a combination of experimental and computational methods. This investigation elucidates their deformation mechanisms and provides numerical parameters crucial in establishing relationships between their geometries and mechanical performance. Three types of lattice were examined, with one, known as the primitive lattice, being found to have a relative elastic modulus over twice as large as those of the other two. The deformation process of the primitive lattice was also considerably different from those of the other two, exhibiting strut stretching and buckling, while the gyroid and diamond lattices deformed in a bending dominated manner. Finite element predictions of the stress distributions in the lattices under compressive loading agreed with experimental observations. These results can be used to create better informed lattice designs for a range of mechanical and biomedical applications.
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•Manufactured and tested lattice structures based on triply periodic minimal surfaces.•Lattices with equivalent masses deform differently depending on their cell geometry.•High stiffness seen for the structure which showed buckling and low failure strain.•Determined Gibson-Ashby factors enabling the design of optimised latticed components.
Objective— To report experience with paranasal sinus surgery through a frontonasal flap in sedated, standing horses.
Study Design— Treatment of 10 horses with naturally occurring paranasal sinus ...disease through a frontonasal bone flap created with the horses standing.
Animals Ten adult horses.
Methods— After restraint and sedation, local anesthetic was injected subcutaneously along the proposed incision line over the conchofrontal sinus and was instilled into the sinuses through a small hole created in the frontal bone. A 3‐sided, rectangular, cutaneous incision that extended through the periosteum was created over the frontal and nasal bones. The incision was extended into the conchofrontal sinus using a bone saw, and the base of the flap, on the midline of the face, was fractured. The sinuses were explored, and the horse was treated for the disease encountered. The flap was repositioned; subcutaneous tissue and skin were sutured separately.
Results— The horses had few signs of discomfort during creation of the bone flap and during disease treatment. Diseases encountered included inspissated exudate in the ventral conchal sinus (five horses), feed and exudate throughout the sinuses (one horse), occlusion of the nasomaxillary aperature (one horse), polyp (one horse), osteoma (one horse), and progressive ethmoidal hematoma (one horse).
Conclusion In selected cases, surgery of the paranasal sinuses can be performed safely on sedated and standing horses through a frontonasal bone flap.
Clinical Relevance— Performing surgery through a frontonasal bone flap with the horse standing and sedated, rather than anesthetized, eliminates risks and expense of general anesthesia.
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