Northern Hemisphere temperature reconstruction during the last millennium using multiple annual proxies

Previous studies have either exclusively used annual tree-ring data or have combined tree-ring series with other, lower temporal resolution proxy series. Both approaches can lead to significant uncertainties, as tree-rings may underestimate the amplitude of past temperature variations, and the validity of non-annual records cannot be clearly assessed. In this study, we assembled 45 published Northern Hemisphere (NH) temperature proxy records covering the past millennium, each of which satisfied 3 essential criteria: the series must be of annual resolution, span at least a thousand years, and represent an explicit temperature signal. Suitable climate archives included ice cores, varved lake sediments, tree-rings and speleothems. We reconstructed the average annual land temperature series for the NH over the last millennium by applying 3 different reconstruction techniques: (1) principal components (PC) plus second-order autoregressive model (AR2), (2) composite plus scale (CPS) and (3) regularized errors-in-variables approach (EIV). Our reconstruction is in excellent agreement with 6 climate model simulations (including the first 5 models derived from the fifth phase of the Coupled Model Intercomparison Project (CMIP5) and an earth system model of intermediate complexity (LOVECLIM), showing similar temperatures at multi-decadal timescales; however, all simulations appear to underestimate the temperature during the Medieval Warm Period (MWP). A comparison with other NH reconstructions shows that our results are consistent with earlier studies. These results indicate that well-validated annual proxy series should be used to minimize proxy-based artifacts, and that these proxy series contain sufficient information to reconstruct the low-frequency climate variability over the past millennium.

Status epilepticus and multiple organ system dysfunction

Recent reports have suggested the possible association of status epilepticus and multiple organ system failure. The purpose of this case control study was to investigate this association and to identify factors that predispose individuals with status epilepticus (SE) or aborted status epilepticus (ASE) to develop multiple organ system failure (MOSF) or multiple organ system dysfunction (MODS).^ For the purpose of the study, definitions of SE, ASE, MOSF, and MODS were operationalized as follows: SE was defined as any seizure lasting for a duration of $\ge$30 minutes or intermittent seizures lasting for $\ge$30 minutes from which the patient does not regain consciousness. ASE was defined as any seizure lasting for a duration of $\ge$10 minutes but $<$30 minutes and which was aborted as a result of a medical intervention. MOSF was defined as the failure of $\ge$2 organ systems in the same patient; organ system failure was said to be present whenever standard MOSF criteria were met. MODS was defined as the dysfunction of $\ge$2 organ systems in the same patient; organ system dysfunction was said to be present, whenever the monitor(s) of that organ's function exceeded the normal range for the physiological or laboratory parameters.^ Medical records of 686 individuals between the age of 5 and 44 years, with history of seizures needing hospitalization at the Texas Children's Hospital or Methodist Hospital, Houston, Texas, between 1991-95 were reviewed and 100 individuals with SE/ASE were identified. Of these 100 individuals with SE/ASE, 45 developed MOSF/MODS during their hospitalization and 9 of these individuals died. Using multivariate analyses, it was found that adult individuals who had an "acute" etiology of their seizure disorder (OR = 5.23; 95%CI: 0.41, 66.24) and children who had a "remote" etiology of their seizure disorder (OR = 3.92; 95%CI: 0.53, 29.22), were more likely to develop MOSF/MODS compared with those who had other etiologies of the seizure disorder. Individuals with SE lasting more than one hour were more likely to develop MOSF/MODS compared with individuals with SE lasting less than 1 hour (OR = 6.51; 95%CI: 1.63, 25.92). Individuals who presented with the SE/ASE episode as their first seizure episode were more likely to develop MOSF/MODS compared to those with a previous history of seizure episodes (OR = 1.78; 95%CI: 0.36, 8.82).^ The major limitations of this study includes the relatively small sample size and the study being performed in only two institutions. However, this is the first study of this kind and should therefore be viewed as largely exploratory in nature. Future studies should investigate the relationship of the risk factors identified in this study using a larger number of institutions and patients. ^

Multiple Sclerosis: Current Knowledge and Future Outlook

Background: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterized by demyelination and axonal loss. The etiology of MS is unknown; however, environmental and genetic factors play a key role in the development of MS. Diagnostic criteria have been adapted to facilitate earlier diagnosis with increased sensitivity and specificity. Our understanding of the pathophysiology of MS has deepened considerably in recent years, resulting in different therapies to modify the disease course. Furthermore, several drugs have lately shown efficacy in phase III studies and their approval is expected in the near future. As treatment options expand, a future challenge will be to find the optimal treatment for the individual patient. Summary: This mini-review gives an overview of the current knowledge of MS with emphasis on the latest diagnostic criteria and both current and upcoming treatment options. Key Messages: Treatment of MS changes rapidly as the knowledge and therapeutic options in MS expand. Clinical Impact: Diagnosis of MS is based on McDonald criteria. MS therapy can be divided into relapse, disease-modifying and symptomatic treatment. Relapses are commonly treated with intravenous methylprednisolone. First-line therapy consists of either interferon-β, glatiramer acetate or teriflunomide. In general, agents used as escalation therapies (natalizumab, fingolimod and mitoxantrone) are more potent than the agents used for first-line therapy; however, these have potentially serious side effects and should be used with care.

All-ceramic or metal-ceramic tooth-supported fixed dental prostheses (FDPs)? A systematic review of the survival and complication rates. Part II: Multiple-unit FDPs.

OBJECTIVE To assess the 5-year survival of metal-ceramic and all-ceramic tooth-supported fixed dental prostheses (FDPs) and to describe the incidence of biological, technical and esthetic complications. METHODS Medline (PubMed), Embase and Cochrane Central Register of Controlled Trials (CENTRAL) searches (2006-2013) were performed for clinical studies focusing on tooth-supported FDPs with a mean follow-up of at least 3 years. This was complemented by an additional hand search and the inclusion of 10 studies from a previous systematic review [1]. Survival and complication rates were analyzed using robust Poisson's regression models to obtain summary estimates of 5-year proportions. RESULTS Forty studies reporting on 1796 metal-ceramic and 1110 all-ceramic FDPs fulfilled the inclusion criteria. Meta-analysis of the included studies indicated an estimated 5-year survival rate of metal-ceramic FDPs of 94.4% (95% CI: 91.2-96.5%). The estimated survival rate of reinforced glass ceramic FDPs was 89.1% (95% CI: 80.4-94.0%), the survival rate of glass-infiltrated alumina FDPs was 86.2% (95% CI: 69.3-94.2%) and the survival rate of densely sintered zirconia FDPs was 90.4% (95% CI: 84.8-94.0%) in 5 years of function. Even though the survival rate of all-ceramic FDPs was lower than for metal-ceramic FDPs, the differences did not reach statistical significance except for the glass-infiltrated alumina FDPs (p=0.05). A significantly higher incidence of caries in abutment teeth was observed for densely sintered zirconia FDPs compared to metal-ceramic FDPs. Significantly more framework fractures were reported for reinforced glass ceramic FDPs (8.0%) and glass-infiltrated alumina FDPs (12.9%) compared to metal-ceramic FDPs (0.6%) and densely sintered zirconia FDPs (1.9%) in 5 years in function. However, the incidence of ceramic fractures and loss of retention was significantly (p=0.018 and 0.028 respectively) higher for densely sintered zirconia FDPs compared to all other types of FDPs. CONCLUSIONS Survival rates of all types of all-ceramic FDPs were lower than those reported for metal-ceramic FDPs. The incidence of framework fractures was significantly higher for reinforced glass ceramic FDPs and infiltrated glass ceramic FDPs, and the incidence for ceramic fractures and loss of retention was significantly higher for densely sintered zirconia FDPs compared to metal-ceramic FDPs.

Use of a modified Delphi panel to identify and weight criteria for prioritization of zoonotic diseases in Switzerland

Zoonotic diseases have a significant impact on public health globally. To prevent or reduce future zoonotic outbreaks, there is a constant need to invest in research and surveillance programs while updating risk management strategies. However, given the limited resources available, disease prioritization based on the need for their control and surveillance is important. This study was performed to identify and weight disease criteria for the prioritization of zoonotic diseases in Switzerland using a semi-quantitative research method based on expert opinion. Twenty-eight criteria relevant for disease control and surveillance, classified under five domains, were selected following a thorough literature review, and these were evaluated and weighted by seven experts from the Swiss Federal Veterinary Office using a modified Delphi panel. The median scores assigned to each criterion were then used to rank 16 notifiable and/or emerging zoonoses in Switzerland. The experts weighted the majority of the criteria similarly, and the top three criteria were Severity of disease in humans, incidence and prevalence of the disease in humans and treatment in humans. Based on these weightings, the three highest ranked diseases were Avian Influenza, Bovine Spongiform Encephalitis, and Bovine Tuberculosis. Overall, this study provided a preliminary list of criteria relevant for disease prioritization in Switzerland. These were further evaluated in a companion study which involved a quantitative prioritization method and multiple stakeholders.

A multi-criteria optimization and decision-making approach for improvement of food engineering processes.

The objective of this study was to propose a multi-criteria optimization and decision-making technique to solve food engineering problems. This technique was demostrated using experimental data obtained on osmotic dehydratation of carrot cubes in a sodium chloride solution. The Aggregating Functions Approach, the Adaptive Random Search Algorithm, and the Penalty Functions Approach were used in this study to compute the initial set of non-dominated or Pareto-optimal solutions. Multiple non-linear regression analysis was performed on a set of experimental data in order to obtain particular multi-objective functions (responses), namely water loss, solute gain, rehydration ratio, three different colour criteria of rehydrated product, and sensory evaluation (organoleptic quality). Two multi-criteria decision-making approaches, the Analytic Hierarchy Process (AHP) and the Tabular Method (TM), were used simultaneously to choose the best alternative among the set of non-dominated solutions. The multi-criteria optimization and decision-making technique proposed in this study can facilitate the assessment of criteria weights, giving rise to a fairer, more consistent, and adequate final compromised solution or food process. This technique can be useful to food scientists in research and education, as well as to engineers involved in the improvement of a variety of food engineering processes.

Strategic sourcing supplier selection misalignment with critical success factors:findings from multiple case studies in Germany and the United Kingdom

Strategic sourcing plays an important role in organisations' performance. Strategic sourcing has been researched extensively using empirical studies as well as review work, such as strategic sourcing importance, issues and challenges, processes, source selection criteria and framework. However, there is no research on critical success factors for strategic sourcing specific to industry and country. This research aims to qualitatively evaluate and understand the current role of strategic sourcing, the critical success factors for business performance and its relationship with strategic sourcing, and strategic supplier evaluation criteria from multiple stakeholders' perspectives specific to industry and country. This research studies twenty organisations from Germany and the United Kingdom (UK) covering two industry sectors - electronics manufacturing and construction. We consider five organisations from each industry sector and each country. The findings from twenty case studies reveal comparative analysis of strategic sourcing practices of two countries and two industries.

Characterization of human mesenchymal stem cells from multiple donors and the implications for large scale bioprocess development

Cell-based therapies have the potential to contribute to global healthcare, whereby the use of living cells and tissues can be used as medicinal therapies. Despite this potential, many challenges remain before the full value of this emerging field can be realized. The characterization of input material for cell-based therapy bioprocesses from multiple donors is necessary to identify and understand the potential implications of input variation on process development. In this work, we have characterized bone marrow derived human mesenchymal stem cells (BM-hMSCs) from multiple donors and discussed the implications of the measurable input variation on the development of autologous and allogeneic cell-based therapy manufacturing processes. The range of cumulative population doublings across the five BM-hMSC lines over 30 days of culture was 5.93, with an 18.2% range in colony forming efficiency at the end of the culture process and a 55.1% difference in the production of interleukin-6 between these cell lines. It has been demonstrated that this variation results in a range in the process time between these donor hMSC lines for a hypothetical product of over 13 days, creating potential batch timing issues when manufacturing products from multiple patients. All BM-hMSC donor lines demonstrated conformity to the ISCT criteria but showed a difference in cell morphology. Metabolite analysis showed that hMSCs from the different donors have a range in glucose consumption of 26.98 pmol cell−1 day−1, Lactate production of 29.45 pmol cell−1 day−1 and ammonium production of 1.35 pmol cell−1 day−1, demonstrating the extent of donor variability throughout the expansion process. Measuring informative product attributes during process development will facilitate progress towards consistent manufacturing processes, a critical step in the translation cell-based therapies.

Comments on multiple oscillatory solutions in systems with time-delay feedback

A complex Ginzburg-Landau equation subjected to local and global time-delay feedback terms is considered. In particular, multiple oscillatory solutions and their properties are studied. We present novel results regarding the disappearance of limit cycle solutions, derive analytical criteria for frequency degeneration, amplitude degeneration, frequency extrema. Furthermore, we discuss the influence of the phase shift parameter and show analytically that the stabilization of the steady state and the decay of all oscillations (amplitude death) cannot happen for global feedback only. Finally, we explain the onset of traveling wave patterns close to the regime of amplitude death.

Exploring the goals, content, and methods of entrepreneurship professors: A multiple case study

Along with the accumulation of evidence supporting the role of entrepreneurship in economic development (Acs & Armington, 2006; Kuratko, 2005, Reynolds, 2007), governments have persisted in encouraging people to become entrepreneurs (Acs & Stough, 2008; Brannback & Carsrud, 2008). These efforts have tried to reproduce the conditions under which entrepreneurship emerges. One of these conditions is to develop entrepreneurial skills among students and scientists (Fan & Foo, 2004). Entrepreneurship education within higher education has experienced a remarkable expansion in the last 20 years (Green, 2008). To develop entrepreneurial skills among students, scholars have proposed different teaching approaches. However, no clear relationship has been demonstrated between entrepreneurship education, learning outcomes, and business creation (Hostager & Decker, 1999). Despite policy makers demands for more accountability from educational institutions (Klimoski, 2007) and entrepreneurship instructors demands for consistency about what should be taught and how (Maidment, 2009), the appropriate content for entrepreneurship programs remains under constant discussion (Solomon, 2007). Entrepreneurship education is still in its infancy, professors propose diverse teaching goals and radically different teaching methods. This represents an obstacle to development of foundational and consistent curricula across the board (Cone, 2008). Entrepreneurship education is in need of a better conceptualization of the learning outcomes pursued in order to develop consistent curriculum. Many schools do not have enough qualified faculty to meet the growing student demand and a consistent curriculum is needed for faculty development. Entrepreneurship instructors and their teaching practices are of interest because they have a role in producing the entrepreneurs needed to grow the economy. This study was designed to understand instructors’ perspectives and actions related to their teaching. The sample studied consisted of eight college and university entrepreneurship instructors. Cases met predetermined criteria of importance followed maximum variation strategies. Results suggest that teaching content were consistent across participants while different teaching goals were identified: some instructors inspire and develop general skills of students while others envision the creation of a real business as the major outcome of their course. A relationship between methods reported by instructors and their disciplinary background, teaching perspective, and entrepreneurial experience was found.

Monitoring the Accuracy of Multiple Occupancy Forecasts

Corporate executives closely monitor the accuracy of their hotels' occupancy fore- casts since important decisions are based upon these predictions. This study lists the criteria for selecting an appropriate error measure. It discusses several evaluation methods focusing on statistical significance tests and demonstrates the use of two adequate evaluation methods: Mincer- Zamowitz's efficiency test and Wilcoxon's Non-Parametric Matched-Pairs Signed- Ranks test.

Group cognitive -behavioral therapy for heterogeneous anxiety disorders in children and adolescents: A multiple baseline study

This study investigated the efficacy of Group Cognitive-Behavioral Therapy (GCBT) in the treatment of heterogeneous anxiety disorders in children. A partially nonconcurrent multiple baseline across groups design was used to assess the effects of the treatment on 12 clinically referred children and adolescents between 6 and 16 years of age who met DSM-IV criteria for an anxiety disorder. Targeted diagnoses included Obsessive Compulsive Disorder, Simple Phobia, Separation Anxiety Disorder, Social Phobia, and Generalized Anxiety Disorder, with three of the children also presenting with school refusal behavior. Duration of baseline for each of the three groups varied and ran for one, two, or three weeks. Dependent measures included diagnostic status, child and parent-completed reports, and daily child and parent ratings of child anxiety severity. Results indicated that GCBT was efficacious in reducing anxious symptoms in children and adolescents treated in diagnostically heterogeneous groups, and that gains were generally maintained at 6 and 12 month follow-ups. Findings are discussed in terms of their theoretical and practical implications for the efficient treatment of children and adolescents with anxiety disorders. ^

Incomplete DJH rearrangements as a novel tumor target for minimal residual disease quantitation in multiple myeloma using real-time PCR.

The hypervariable regions of immunoglobulin heavy-chain (IgH) rearrangements provide a specific tumor marker in multiple myeloma (MM). Recently, real-time PCR assays have been developed in order to quantify the number of tumor cells after treatment. However, these strategies are hampered by the presence of somatic hypermutation (SH) in VDJH rearrangements from multiple myeloma (MM) patients, which causes mismatches between primers and/or probes and the target, leading to a nonaccurate quantification of tumor cells. Our group has recently described a 60% incidence of incomplete DJH rearrangements in MM patients, with no or very low rates of SH. In this study, we compare the efficiency of a real-time PCR approach for the analysis of both complete and incomplete IgH rearrangements in eight MM patients using only three JH consensus probes. We were able to design an allele-specific oligonucleotide for both the complete and incomplete rearrangement in all patients. DJH rearrangements fulfilled the criteria of effectiveness for real-time PCR in all samples (ie no unspecific amplification, detection of less than 10 tumor cells within 10(5) polyclonal background and correlation coefficients of standard curves higher than 0.98). By contrast, only three out of eight VDJH rearrangements fulfilled these criteria. Further analyses showed that the remaining five VDJH rearrangements carried three or more somatic mutations in the probe and primer sites, leading to a dramatic decrease in the melting temperature. These results support the use of incomplete DJH rearrangements instead of complete somatically mutated VDJH rearrangements for investigation of minimal residual disease in multiple myeloma.

Joint Analysis of Multiple Algorithms and Performance Measures

There has been an increasing interest in the development of new methods using Pareto optimality to deal with multi-objective criteria (for example, accuracy and time complexity). Once one has developed an approach to a problem of interest, the problem is then how to compare it with the state of art. In machine learning, algorithms are typically evaluated by comparing their performance on different data sets by means of statistical tests. Standard tests used for this purpose are able to consider jointly neither performance measures nor multiple competitors at once. The aim of this paper is to resolve these issues by developing statistical procedures that are able to account for multiple competing measures at the same time and to compare multiple algorithms altogether. In particular, we develop two tests: a frequentist procedure based on the generalized likelihood-ratio test and a Bayesian procedure based on a multinomial-Dirichlet conjugate model. We further extend them by discovering conditional independences among measures to reduce the number of parameters of such models, as usually the number of studied cases is very reduced in such comparisons. Data from a comparison among general purpose classifiers is used to show a practical application of our tests.

Secure Multiple Amplify-and-Forward Relaying with Co-Channel Interference

We investigate the impact of co-channel interference on the security performance of multiple amplify-and-forward (AF) relaying networks, where N intermediate AF relays assist the data transmission from the source to the destination. The relays are corrupted by multiple co-channel interferers, and the information transmitted from the relays to destination can be overheard by the eavesdropper. In order to deal with the interference and wiretap, the best out of N relays is selected for security enhancement. To this end, we derive a novel lower bound on the secrecy outage probability (SOP), which is then utilized to present two best relay selection criteria, based on the instantaneous and statistical channel information of the interfering links. For these criteria and the conventional maxmin criterion, we quantify the impact of co-channel interference and relay selection by deriving the lower bound on the SOP. Furthermore, we derive the asymptotic SOP for each criterion, to explicitly reveal the impact of transmit power allocation among interferers on the secrecy performance, which offers valuable insights into practical design. We demonstrate that all selection criteria achieve full secrecy diversity order N, while the proposed in this paper two criteria outperform the conventional max-min scheme.