Dynamic walking features and improved walking performance in multiple sclerosis patients treated with fampridine (4-aminopyridine)

Background: Impaired walking capacity is a frequent confinement in Multiple Sclerosis (MS). Patients are affected by limitations in coordination, walking speed and the distance they may cover. Also abnormal dynamic walking patterns have been reported, involving continuous deceleration over time. Fampridine (4-aminopyridine), a potassium channel blocker, may improve walking in MS. The objective of the current study was to comprehensively examine dynamic walking characteristics and improved walking capacity in MS patients treated with fampridine. Methods: A sample of N = 35 MS patients (EDSS median: 4) underwent an electronic walking examination prior to (Time 1), and during treatment with fampridine (Time 2). Patients walked back and forth a distance of 25 ft for a maximum period of 6 min (6-minute 25-foot-walk). Besides the total distance covered, average speed on the 25-foot distance and on turns was determined separately for each test minute, at Time 1 and Time 2. Results: Prior to fampridine administration, 27/35 patients (77 %) were able to complete the entire 6 min of walking, while following the administration, 34/35 patients (97 %) managed to walk for 6 min. In this context, walking distance considerably increased and treatment was associated with faster walking and turning across all six test minutes (range of effect sizes: partial eta squared = .34-.72). Importantly, previously reported deceleration across test minutes was consistently observable at Time 1 and Time 2. Discussion: Fampridine administration is associated with improved walking speed and endurance. Regardless of a treatment effect of fampridine, the previously identified, abnormal dynamic walking feature, i.e. the linear decline in walking speed, may represent a robust feature. Conclusions: The dynamic walking feature might hence be considered as a candidate for a new outcome measure in clinical studies involving interventions other than symptomatic treatment, such as immune-modulating medication. Trial registration: DRKS00009228 (German Clinical Trials Register). Date obtained: 25.08.2015

A systematic review of treating recurrent head and neck cancer: a reintroduction of brachytherapy with or without surgery.

Purpose: To review brachytherapy use in recurrent head and neck carcinoma (RHNC) with focus on its efficacy and complication rates. Material and methods: A literature search of PubMed, Ovid, Google Scholar, and Scopus was conducted from 1990 to 2017. Publications describing treatment of RHNC with brachytherapy with or without surgery were included. The focus of this review is on oncologic outcomes and the safety of brachytherapy in the recurrent setting. Results: Thirty studies involving RHNC treatment with brachytherapy were reviewed. Brachytherapy as adjunctive treatment to surgical resection appears to be associated with an improved local regional control and overall survival, when compared with the published rates for re-irradiation utilizing external beam radiotherapy (RT) or brachytherapy alone. Safety data remains variable with different isotopes and dose rates with implantable brachytherapy demonstrating a tolerable side effect profile. Conclusions: Although surgery remains a mainstay treatment for RHNC, intraoperative interstitial brachytherapy delivery as adjunctive therapy may improve the treatment outcome and may be associated with fewer complication rates as compared to reirradiation using external beam radiotherapy. Further investigations are required to elucidate the role of brachytherapy for RHNC

A conceptual framework for graduate teaching assistant professional development evaluation and research

© 2016 T. D. Reeves et al. Biology graduate teaching assistants (GTAs) are significant contributors to the educational mission of universities, particularly in introductory courses, yet there is a lack of empirical data on how to best prepare them for their teaching roles. This essay proposes a conceptual framework for biology GTA teaching professional development (TPD) program evaluation and research with three overarching variable categories for consideration: outcome variables, contextual variables, and moderating variables. The framework’s outcome variables go beyond GTA satisfaction and instead position GTA cognition, GTA teaching practice, and undergraduate learning outcomes as the foci of GTA TPD evaluation and research. For each GTA TPD outcome variable, key evaluation questions and example assessment instruments are introduced to demonstrate how the framework can be used to guide GTA TPD evaluation and research plans. A common conceptual framework is also essential to coordinating the collection and synthesis of empirical data on GTA TPD nationally. Thus, the proposed conceptual framework serves as both a guide for conducting GTA TPD evaluation at single institutions and as a means to coordinate research across institutions at a national level

Experiences, Opportunities and Challenges of Implementing Task Shifting in Underserved Remote Settings: The Case of Kongwa District, Central Tanzania.

Tanzania is experiencing acute shortages of Health Workers (HWs), a situation which has forced health managers, especially in the underserved districts, to hastily cope with health workers' shortages by adopting task shifting. This has however been due to limited options for dealing with the crisis of health personnel. There are on-going discussions in the country on whether to scale up task shifting as one of the strategies for addressing health personnel crisis. However, these discussions are not backed up by rigorous scientific evidence. The aim of this paper is two-fold. Firstly, to describe the current situation of implementing task shifting in the context of acute shortages of health workers and, secondly, to provide a descriptive account of the potential opportunities or benefits and the likely challenges which might ensue as a result of implementing task shifting. We employed in-depth interviews with informants at the district level and supplemented the information with additional interviews with informants at the national level. Interviews focussed on the informants' practical experiences of implementing task shifting in their respective health facilities (district level) and their opinions regarding opportunities and challenges which might be associated with implementation of task shifting practices. At the national level, the main focus was on policy issues related to management of health personnel in the context of implementation of task shifting, in addition to seeking their opinions and perceptions regarding opportunities and challenges of implementing task shifting if formally adopted. Task shifting has been in practice for many years in Tanzania and has been perceived as an inevitable coping mechanism due to limited options for addressing health personnel shortages in the country. Majority of informants had the concern that quality of services is likely to be affected if appropriate policy infrastructures are not in place before formalising tasks shifting. There was also a perception that implementation of task shifting has ensured access to services especially in underserved remote areas. Professional discontent and challenges related to the management of health personnel policies were also perceived as important issues to consider when implementing task shifting practices. Additional resources for additional training and supervisory tasks were also considered important in the implementation of task shifting in order to make it deliver much the same way as it is for conventional modalities of delivering care. Task shifting implementation occurs as an ad hoc coping mechanism to the existing shortages of health workers in many undeserved areas of the country, not just in the study site whose findings are reported in this paper. It is recommended that the most important thing to do now is not to determine whether task shifting is possible or effective but to define the limits of task shifting so as to reach a consensus on where it can have the strongest and most sustainable impact in the delivery of quality health services. Any action towards this end needs to be evidence-based

Mid-infrared optical parametric amplifier using silicon nanophotonic waveguides

All-optical signal processing is envisioned as an approach to dramatically decrease power consumption and speed up performance of next-generation optical telecommunications networks. Nonlinear optical effects, such as four-wave mixing (FWM) and parametric gain, have long been explored to realize all-optical functions in glass fibers. An alternative approach is to employ nanoscale engineering of silicon waveguides to enhance the optical nonlinearities by up to five orders of magnitude, enabling integrated chip-scale all-optical signal processing. Previously, strong two-photon absorption (TPA) of the telecom-band pump has been a fundamental and unavoidable obstacle, limiting parametric gain to values on the order of a few dB. Here we demonstrate a silicon nanophotonic optical parametric amplifier exhibiting gain as large as 25.4 dB, by operating the pump in the mid-IR near one-half the band-gap energy (E~0.55eV, lambda~2200nm), at which parasitic TPA-related absorption vanishes. This gain is high enough to compensate all insertion losses, resulting in 13 dB net off-chip amplification. Furthermore, dispersion engineering dramatically increases the gain bandwidth to more than 220 nm, all realized using an ultra-compact 4 mm silicon chip. Beyond its significant relevance to all-optical signal processing, the broadband parametric gain also facilitates the simultaneous generation of multiple on-chip mid-IR sources through cascaded FWM, covering a 500 nm spectral range. Together, these results provide a foundation for the construction of silicon-based room-temperature mid-IR light sources including tunable chip-scale parametric oscillators, optical frequency combs, and supercontinuum generators

Bridging the Mid-Infrared-to-Telecom Gap with Silicon Nanophotonic Spectral Translation

Expanding far beyond traditional applications in optical interconnects at telecommunications wavelengths, the silicon nanophotonic integrated circuit platform has recently proven its merits for working with mid-infrared (mid-IR) optical signals in the 2-8 {\mu}m range. Mid-IR integrated optical systems are capable of addressing applications including industrial process and environmental monitoring, threat detection, medical diagnostics, and free-space communication. Rapid progress has led to the demonstration of various silicon components designed for the on-chip processing of mid-IR signals, including waveguides, vertical grating couplers, microcavities, and electrooptic modulators. Even so, a notable obstacle to the continued advancement of chip-scale systems is imposed by the narrow-bandgap semiconductors, such as InSb and HgCdTe, traditionally used to convert mid-IR photons to electrical currents. The cryogenic or multi-stage thermo-electric cooling required to suppress dark current noise, exponentially dependent upon the ratio Eg/kT, can limit the development of small, low-power, and low-cost integrated optical systems for the mid-IR. However, if the mid-IR optical signal could be spectrally translated to shorter wavelengths, for example within the near-infrared telecom band, photodetectors using wider bandgap semiconductors such as InGaAs or Ge could be used to eliminate prohibitive cooling requirements. Moreover, telecom band detectors typically perform with higher detectivity and faster response times when compared with their mid-IR counterparts. Here we address these challenges with a silicon-integrated approach to spectral translation, by employing efficient four-wave mixing (FWM) and large optical parametric gain in silicon nanophotonic wires

Development of a decision support tool to facilitate primary care management of patients with abnormal liver function tests without clinically apparent liver disease [HTA03/38/02]. Abnormal Liver Function Investigations Evaluation (ALFIE)

Liver function tests (LFTs) are routinely performed in primary care, and are often the gateway to further invasive and/or expensive investigations. Little is known of the consequences in people with an initial abnormal liver function (ALF) test in primary care and with no obvious liver disease. Further investigations may be dangerous for the patient and expensive for Health Services. The aims of this study are to determine the natural history of abnormalities in LFTs before overt liver disease presents in the population and identify those who require minimal further investigations with the potential for reduction in NHS costs

Streptococcus pneumoniae enhances human respiratory syncytial virus infection in vitro and in vivo

Human respiratory syncytial virus (HRSV) and Streptococcus pneumoniae are important causative agents of respiratory tract infections. Both pathogens are associated with seasonal disease outbreaks in the pediatric population, and can often be detected simultaneously in infants hospitalized with bronchiolitis or pneumonia. It has been described that respiratory virus infections may predispose for bacterial superinfections, resulting in severe disease. However, studies on the influence of bacterial colonization of the upper respiratory tract on the pathogenesis of subsequent respiratory virus infections are scarce. Here, we have investigated whether pneumococcal colonization enhances subsequent HRSV infection. We used a newly generated recombinant subgroup B HRSV strain that expresses enhanced green fluorescent protein and pneumococcal isolates obtained from healthy children in disease-relevant in vitro and in vivo model systems. Three pneumococcal strains specifically enhanced in vitro HRSV infection of primary well-differentiated normal human bronchial epithelial cells grown at air-liquid interface, whereas two other strains did not. Since previous studies reported that bacterial neuraminidase enhanced HRSV infection in vitro, we measured pneumococcal neuraminidase activity in these cultures but found no correlation with the observed infection enhancement in our model. Subsequently, a selection of pneumococcal strains was used to induce nasal colonization of cotton rats, the best available small animal model for HRSV. Intranasal HRSV infection three days later resulted in strain-specific enhancement of HRSV replication in vivo. One S. pneumoniae strain enhanced HRSV both in vitro and in vivo, and was also associated with enhanced syncytium formation in vivo. However, neither pneumococci nor HRSV were found to spread from the upper to the lower respiratory tract, and neither pathogen was transmitted to naive cage mates by direct contact. These results demonstrate that pneumococcal colonization can enhance subsequent HRSV infection, and provide tools for additional mechanistic and intervention studies

Generation of Functional CLL-Specific Cord Blood CTL Using CD40-Ligated CLL APC

PMCID: PMC3526610This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited