Asymptomatic lacrimal flow abnormalities in patients with septal deviations and turbinate hypertrophy

Background: This study aimed to investigate the lacrimal flow in patients affected by septal deviations and turbinate hypertrophy and to evaluate changes after rhinoseptoplasty with dacryocystography (DCT) and computed tomographic dacryocystography (CT-DCT). Methods: The study prospectively recruited patients having septal deviations with or without turbinate hypertrophy who underwent surgical evaluation for correction of their respiratory symptoms and were not referred for epiphora. Patients were excluded if they had undergone surgery for cranial vault defects or had experienced septal deviations after traumatic accidents. All patients were studied with DCT and CT-DCT preoperatively and postoperatively. Results: A total of 24 patients (10 men and 14 women) were recruited for the study. Of these patients, 11 (45.8%) had a reduced flow of the medium contrast due to a partial obstruction at the level of the internal ostium. All 11 patients had septal deviations and turbinate hypertrophy, whereas 8 patients had a unilateral obstruction (72.7%), and 3 patients had a bilateral obstruction (27.3%). All flows were corrected after surgery. Conclusions:The safe and well-tolerated radiologic techniques performed in this study provided detailed imaging of the lacrimal outflow system. A high incidence of partial obstruction to the internal ostium was found in patients with septal deviations, turbinate hypertrophy, and no lacrimal symptoms, suggesting a frequent presymptomatic condition

An empirical analysis of supply and manufacturing risk and business performance: A Chinese manufacturing supply chain perspective

Purpose – This study explores the importance and impact of supply and manufacturing risk management upon business performance within the context of Chinese manufacturing supply chains. Design/Methodology/Approach – A two phased multi-method approach was adopted, which included a survey questionnaire to practitioners in Chinese manufacturing supply chains followed by semi-structured interviews. The findings included 103 valid survey responses complemented by six semi-structured interviews. Findings – The results indicate that in Chinese manufacturing context supply risk and manufacturing risk management are both vital for business performance. A high correlation between business and manufacturing risk management performance exists, however no significant impact of supplier dependency, systematic purchasing, maturity of production and supply chain, and human resources was found despite previously these elements being regarded as key influencers for supply and manufacturing risk management performance. The Chinese manufacturing supply chain indicated that elements such as the supplier and customer orientation, flexibility, manufacturing and supply risk highly connotes with business performance. Theoretical/Practical implications – In the current unpredictable and volatile business environment the competitiveness of manufacturing supply chains to a large extent depend on their ability to identify, assess and manage the manufacturing and supply risks. The findings of this study will assist supply chain managers in taking decision on manufacturing and supply risk management and reducing the uncertainty upon their business performance. Originality/value – The supply chain risk has been widely explored within the context of individual case studies, or standalone models focusing on either supply or manufacturing risk in supply chains, however to what extent this has been applicable to a wider context and its impact upon business process has not been explored. Hence, this study simultaneously has analysed manufacturing risk and supply risk and its impact upon Chinese manufacturing supply chains business performance. Moreover, this study uses a combination of quantitative and qualitative methods, which is often limited in this area. Finally, the institutional theory lens offers novel insights in better understanding the factors that can affect the impact of supply and manufacturing risk management upon business performance in those contexts, such as China, where the institutional aspect presents specific features

The MRN complex is transcriptionally regulated by MYCN during neural cell proliferation to control replication stress

The MRE11/RAD50/NBS1 (MRN) complex is a major sensor of DNA double strand breaks, whose role in controlling faithful DNA replication and preventing replication stress is also emerging. Inactivation of the MRN complex invariably leads to developmental and/or degenerative neuronal defects, the pathogenesis of which still remains poorly understood. In particular, NBS1 gene mutations are associated with microcephaly and strongly impaired cerebellar development, both in humans and in the mouse model. These phenotypes strikingly overlap those induced by inactivation of MYCN, an essential promoter of the expansion of neuronal stem and progenitor cells, suggesting that MYCN and the MRN complex might be connected on a unique pathway essential for the safe expansion of neuronal cells. Here, we show that MYCN transcriptionally controls the expression of each component of the MRN complex. By genetic and pharmacological inhibition of the MRN complex in a MYCN overexpression model and in the more physiological context of the Hedgehog-dependent expansion of primary cerebellar granule progenitor cells, we also show that the MRN complex is required for MYCN-dependent proliferation. Indeed, its inhibition resulted in DNA damage, activation of a DNA damage response, and cell death in a MYCN- and replication-dependent manner. Our data indicate the MRN complex is essential to restrain MYCN-induced replication stress during neural cell proliferation and support the hypothesis that replication-born DNA damage is responsible for the neuronal defects associated with MRN dysfunctions.Cell Death and Differentiation advance online publication, 12 June 2015; doi:10.1038/cdd.2015.81

Dual-site right ventricular pacing in patients undergoing cardiac resynchronization therapy: Results of a multicenter propensity-matched analysis

BACKGROUND: Dual-site right ventricular pacing (Dual RV) has been proposed as an alternative for patients with heart failure undergoing cardiac resynchronization therapy (CRT) with a failure to deliver a coronary sinus (CS) lead. Only short-term hemodynamic and echocardiographic results of Dual RV are available. We aimed to assess the long-term results of Dual RV and its impact on survival. METHODS: Multicenter retrospective assessment of all CRT implants during a 12-year period. Patients with failed CS lead implantation, treated with Dual RV, were followed and assessed for the primary endpoint of all-cause mortality and/or heart transplant. A control group was obtained from contemporary patients using propensity matching for all available baseline variables. RESULTS: Ninety-three patients were implanted with Dual RV devices and compared with 93 matched controls. During a median of 1,273 days (interquartile range 557-2,218), intention-to-treat analysis showed that all-cause mortality and/or heart transplant was higher in the Dual RV group (adjusted hazard ratio [HR] = 1.66, 95% confidence interval [CI] 1.12-2.47, P = 0.012). As-treated analysis yielded similar results (HR = 1.97, 95% CI 1.31-2.96, P = 0.001). Cardiac device-related infections occurred seven times more frequently in the Dual RV site group (HR = 7.60, 95% CI 1.51-38.33, P = 0.014). Among Dual RV nonresponders, four had their apical leads switched off, five required an epicardial LV lead insertion, a transseptal LV lead was implanted in two, and in nine patients, after reviewing the CS venogram, a new CS lead insertion was successfully attempted. CONCLUSION: Dual RV pacing is associated with worse clinical outcomes and higher complication rates than conventional CRT

The Rippling Effect of Non-linearities

Non-linearities can lead to unexpected dynamic behaviours in supply chain systems that could then either trigger disruptions or make the response and recovery process more difficult. In this chapter, we take a control-theoretic perspective to discuss the impact of non-linearities on the ripple effect. This chapter is particularly relevant for researchers wanting to learn more about the different types of non-linearities that can be found in supply chain systems, the existing analytical methods to deal with each type of non-linearity and future scope for research based on the current knowledge in this field

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

A Systematic Literature Review of Supply Chain Resilience in Small–Medium Enterprises (SMEs): A Call for Further Research

In this article, with the increased disruptions faced by businesses and the occurrence of natural disasters in the world, supply chain resilience remains a major challenge especially for small- and medium-sized enterprises (SMEs). Despite the relevance of SMEs to the economy, there is limited scholarly work on resilience practices in SMEs and a limited understanding of how SMEs can achieve resilience. To understand the role of supply chain resilience in SMEs, we undertake a systematic literature review (SLR), which results in the identification and analysis of 101 journal articles, published between 2006 and 2019, on SME supply chain resilience. Our analysis into SME supply chain resilience highlights four focal areas: 1) the role of collaboration and culture; 2) the role of SMEs’ capabilities; 3) the role of Information Systems; and (4) the role of cost and financing. Our SLR investigation identifies future research directions and focal areas tailored to SMEs to help them to assess and develop their supply chain resilience

The MRN complex is transcriptionally regulated by MYCN during neural cell proliferation to control replication stress

The MRE11/RAD50/NBS1 (MRN) complex is a major sensor of DNA double strand breaks, whose role in controlling faithful DNA replication and preventing replication stress is also emerging. Inactivation of the MRN complex invariably leads to developmental and/or degenerative neuronal defects, the pathogenesis of which still remains poorly understood. In particular, NBS1 gene mutations are associated with microcephaly and strongly impaired cerebellar development, both in humans and in the mouse model. These phenotypes strikingly overlap those induced by inactivation of MYCN, an essential promoter of the expansion of neuronal stem and progenitor cells, suggesting that MYCN and the MRN complex might be connected on a unique pathway essential for the safe expansion of neuronal cells. Here, we show that MYCN transcriptionally controls the expression of each component of the MRN complex. By genetic and pharmacological inhibition of the MRN complex in a MYCN overexpression model and in the more physiological context of the Hedgehog-dependent expansion of primary cerebellar granule progenitor cells, we also show that the MRN complex is required for MYCN-dependent proliferation. Indeed, its inhibition resulted in DNA damage, activation of a DNA damage response, and cell death in a MYCN- and replication-dependent manner. Our data indicate the MRN complex is essential to restrain MYCN-induced replication stress during neural cell proliferation and support the hypothesis that replication-born DNA damage is responsible for the neuronal defects associated with MRN dysfunctions

Alternative techniques in reconstructive surgery: Bone-anchored extraoral implants for burn cases

Background The authors present their experience with the use of extraoral implants for reconstruction of the ear area after burns. The first step of the protocol includes positioning of implants in the mastoid process. The second step, after 3 to 4 months, is to realize the auricle prosthesis and apply it. Extraoral, bone-integrated implants offer low surgical risks and few postsurgical complications, leading to optimal aesthetic results, mainly in the ear area. Compared with traditional surgery techniques, the aesthetic results are better, with less surgery, possibly only two surgery sessions. Adhesive prostheses can be placed without the usual local irritation, and a more correct positioning can be obtained. Methods For this study, two female patients, treated from December 2001 to January 2005, were selected to receive auricle epitheses. In the authors' experience, 79% of case reporting describes the creation of this epithesis type. The patient age has a range of 26 years. The two study patients initially had the same diagnosis: burns of the auricle-temporal region. Results In all cases, a good aesthetic result was obtained. Conclusions The authors believe that bone-anchored implants for the treatment of auricle burns is a valid and brilliant technique that complements traditional reconstructive procedures. The advantages are the low incidence of long-term complications and the possibility of obtaining excellent aesthetic lasting results even for very complicated cases that would not have been solved in the past