British Neurotoxin Network recommendations for managing cervical dystonia in patients with a poor response to botulinum toxin

Botulinum toxin (BoNT) injections are an effective treatment for cervical dystonia. Approximately 20% of patients eventually stop BoNT treatment, mostly because of treatment failure. These recommendations review the different therapeutic interventions for optimising the treatment in secondary poor responder patients. Immunoresistance has become less common over the years, but the diagnosis has to be addressed with a frontalis test or an Extensor Digitorum Brevis test. In case of immunoresistance to BoNTA, we discuss the place the different therapeutic options (BoNT-A holidays, BoNT-B injections, alternative BoNT-A injections, deep brain stimulation). When poor responders are not immunoresistant, they benefit from reviewing (1) injections technique with electromyography or ultrasound guidance, (2) muscles selection and (3) dose of BoNT. In addition, in both scenarios, a holistic approach including drug treatment, retraining and psychological support is valuable in the management of these complex and severe cervical dystonia

Small-amplitude normal modes of a vortex in a trapped Bose-Einstein condensate

We consider a cylindrically symmetric trap containing a small Bose-Einstein condensate with a singly quantized vortex on the axis of symmetry. A time-dependent variational Lagrangian analysis yields the small-amplitude dynamics of the vortex and the condensate, directly determining the equations of motion of the coupled normal modes. As found previously from the Bogoliubov equations, there are two rigid dipole modes and one anomalous mode with a negative frequency when seen in the laboratory frame.Comment: 4 pages, no figures, Revte

Hoe cultureel is de digitale generatie?

Over the past decade, young people in the Netherlands have developed into fervent Internet users. At the same time, cultural institutions have digitised a great deal of their content and made it accessible online. This was seen as a challenging combination, or a new opportunity to reach this target audience, since most young people are online. It is however unclear how much use the digital generation actually makes of the online opportunities for cultural purposes. This report describes how culturally active teenagers are on the Internet and to what extent their cultural activities are related to the extent of their Internet use, their digital skills, the cultural activities of their family and friends, and the (cultural and digital) activities at their school. For this study, 1592 Dutch secondary school students were interviewed in 2008, with questionnaires being completed by students in 167 classes at 32 schools distributed across five large cities, 11 medium-sized cities and three small municipalities. The students varied in age from 12 to 18 years and were attending courses at pre-vocational secondary, senior general secondary or pre-university level (students in final examination classes were not interviewed). In order to investigate the digital cultural participation of 12-18 year-olds, a distinction was made between three types of Internet use. These can be summarised using three ‘C’s: − content (using the Internet to search for various kinds of information, such as text, images and sound); − contact (personal communication or interaction in peer-to-peer networks); − creation (production of text, images or sound and uploading these to the Internet, as well as responding online to contributions from others and posting tags).In het afgelopen decennium hebben jongeren zich geprofileerd als fervente internetgebruikers. Tegelijkertijd hebben culturele instellingen veel aanbod gedigitaliseerd en online toegankelijk gemaakt. Dit werd als een uitdagende combinatie of een nieuwe kans gezien, aangezien de meeste jongeren online zijn. Het is echter de vraag in hoeverre de digitale generatie de online mogelijkheden inderdaad benut voor culturele doeleinden. In dit rapport is beschreven hoe cultureel actief tieners op internet zijn en in hoeverre die activiteiten samenhangen met de omvang van hun internetgebruik, hun digitale vaardigheden, de culturele activiteiten in hun gezin en van hun vrienden, en de (culturele en digitale) activiteiten op hun school. Voor het onderzoek zijn leerlingen in het voortgezet onderwijs geïnterviewd. In 2008 vulden 1592 leerlingen uit 167 klassen van 32 scholen in de klas een vragenlijst in. De scholen zijn verdeeld over vijf grote steden, elf middelgrote steden en drie kleine gemeenten. De leerlingen varieerden in leeftijd tussen de 12 en 18 jaar en zaten op een vmbo-, havo- of vwo-opleiding (leerlingen in eindexamenklassen zijn niet ondervraagd). Om de digitale cultuurparticipatie van 12-18-jarige scholieren te onderzoeken is een onderscheid gemaakt in drie rollen bij het internetgebruik. Deze drie rollen kunnen samengevat worden met drie C’s: − content (gebruik internet voor verschillende soorten informatie zoals tekst, beeld als geluid); − contact (persoonlijke communicatie of interactie in peer-to-peer-netwerken); − creatie (het zelf produceren van tekst, beeld of geluid en deze uploaden op internetalsmede het online reageren op bijdragen van anderen en het plaatsen van tags)

Dissociating the semantic function of two neighbouring subregions in the left lateral anterior temporal lobe

AbstractWe used fMRI in 35 healthy participants to investigate how two neighbouring subregions in the lateral anterior temporal lobe (LATL) contribute to semantic matching and object naming. Four different levels of processing were considered: (A) recognition of the object concepts; (B) search for semantic associations related to object stimuli; (C) retrieval of semantic concepts of interest; and (D) retrieval of stimulus specific concepts as required for naming. During semantic association matching on picture stimuli or heard object names, we found that activation in both subregions was higher when the objects were semantically related (mug–kettle) than unrelated (car–teapot). This is consistent with both LATL subregions playing a role in (C), the successful retrieval of amodal semantic concepts. In addition, one subregion was more activated for object naming than matching semantically related objects, consistent with (D), the retrieval of a specific concept for naming. We discuss the implications of these novel findings for cognitive models of semantic processing and left anterior temporal lobe function

Limited effect of duration of CMV infection on adaptive immunity and frailty:insights from a 27-year-long longitudinal study

Objectives: Cytomegalovirus infection is thought to affect the immune system and to impact general health during ageing. Higher CMV-specific antibody levels in the elderly are generally assumed to reflect experienced viral reactivation during life. Furthermore, high levels of terminally differentiated and CMV-specific T cells are hallmarks of CMV infection, which are thought to expand over time, a process also referred to as memory inflation.Methods: We studied CMV-specific antibody levels over ~ 27 years in 268 individuals (aged 60-89 years at study endpoint), and to link duration of CMV infection to T-cell numbers, CMV-specific T-cell functions, frailty and cardiovascular disease at study endpoint.Results: In our study, 136/268 individuals were long-term CMV seropositive and 19 seroconverted during follow-up (seroconversion rate: 0.56%/year). CMV-specific antibody levels increased slightly over time. However, we did not find an association between duration of CMV infection and CMV-specific antibody levels at study endpoint. No clear association between duration of CMV infection and the size and function of the memory T-cell pool was observed. Elevated CMV-specific antibody levels were associated with the prevalence of cardiovascular disease but not with frailty. Age at CMV seroconversion was positively associated with CMV-specific antibody levels, memory CD4+ T-cell numbers and frailty.Conclusion: Cytomegalovirus-specific memory T cells develop shortly after CMV seroconversion but do not seem to further increase over time. Age-related effects other than duration of CMV infection seem to contribute to CMV-induced changes in the immune system. Although CMV-specific immunity is not evidently linked to frailty, it tends to associate with higher prevalence of cardiovascular disease.</p

Inheritance of deleterious mutations at both BRCA1 and BRCA2 in an international sample of 32,295 women

Background: Most BRCA1 or BRCA2 mutation carriers have inherited a single (heterozygous) mutation. Transheterozygotes (TH) who have inherited deleterious mutations in both BRCA1 and BRCA2 are rare, and the consequences of transheterozygosity are poorly understood. Methods: From 32,295 female BRCA1/2 mutation carriers, we identified 93 TH (0.3 %). "Cases" were defined as TH, and "controls" were single mutations at BRCA1 (SH1) or BRCA2 (SH2). Matched SH1 "controls" carried a BRCA1 mutation found in the TH "case". Matched SH2 "controls" carried a BRCA2 mutation found in the TH "case". After matching the TH carriers with SH1 or SH2, 91 TH were matched to 9316 SH1, and 89 TH were matched to 3370 SH2. Results: The majority of TH (45.2 %) involved the three common Jewish mutations. TH were more likely than SH1 and SH2 women to have been ever diagnosed with breast cancer (BC; p = 0.002). TH were more likely to be diagnosed with ovarian cancer (OC) than SH2 (p = 0.017), but not SH1. Age at BC diagnosis was the same in TH vs. SH1 (p = 0.231), but was on average 4.5 years younger in TH than in SH2 (p < 0.001). BC in TH was more likely to be estrogen receptor (ER) positive (p = 0.010) or progesterone receptor (PR) positive (p = 0.013) than in SH1, but less likely to be ER positive (p < 0.001) or PR positive (p = 0.012) than SH2. Among 15 tumors from TH patients, there was no clear pattern of loss of heterozygosity (LOH) for BRCA1 or BRCA2 in either BC or OC. Conclusions: Our observations suggest that clinical TH phenotypes resemble SH1. However, TH breast tumor marker characteristics are phenotypically intermediate to SH1 and SH2

The Public Repository of Xenografts enables discovery and randomized phase II-like trials in mice

More than 90% of drugs with preclinical activity fail in human trials, largely due to insufficient efficacy. We hypothesized that adequately powered trials of patient-derived xenografts (PDX) in mice could efficiently define therapeutic activity across heterogeneous tumors. To address this hypothesis, we established a large, publicly available repository of well-characterized leukemia and lymphoma PDXs that undergo orthotopic engraftment, called the Public Repository of Xenografts (PRoXe). PRoXe includes all de-identified information relevant to the primary specimens and the PDXs derived from them. Using this repository, we demonstrate that large studies of acute leukemia PDXs that mimic human randomized clinical trials can characterize drug efficacy and generate transcriptional, functional, and proteomic biomarkers in both treatment-naive and relapsed/refractory disease