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The importance of the hippocampus and amygdala for disrupted emotional memory formation in depression is well-recognized, but it remains unclear whether functional abnormalities are state-dependent and whether they are affected by the persistence of depressive symptoms.
Thirty-nine patients with major depressive disorder and 28 healthy controls were included from the longitudinal functional magnetic resonance imaging (fMRI) sub-study of the Netherlands Study of Depression and Anxiety. Participants performed an emotional word-encoding and -recognition task during fMRI at baseline and 2-year follow-up measurement. At baseline, all patients were in a depressed state. We investigated state-dependency by relating changes in brain activation over time to changes in symptom severity. Furthermore, the effect of time spent with depressive symptoms in the 2-year interval was investigated.
Symptom change was linearly associated with higher activation over time of the left anterior hippocampus extending to the amygdala during positive and negative word-encoding. Especially during positive word encoding, this effect was driven by symptomatic improvement. There was no effect of time spent with depression in the 2-year interval on change in brain activation. Results were independent of medication- and psychotherapy-use.
Using a longitudinal within-subjects design, we showed that hippocampal–amygdalar activation during emotional memory formation is related to depressive symptom severity but not persistence (i.e. time spent with depression or ‘load’), suggesting functional activation patterns in depression are not subject to functional ‘scarring’ although this hypothesis awaits future replication.
Childhood maltreatment (CM) plays an important role in the development of major depressive disorder (MDD). The aim of this study was to examine whether CM severity and type are associated with MDD-related brain alterations, and how they interact with sex and age.
Within the ENIGMA-MDD network, severity and subtypes of CM using the Childhood Trauma Questionnaire were assessed and structural magnetic resonance imaging data from patients with MDD and healthy controls were analyzed in a mega-analysis comprising a total of 3872 participants aged between 13 and 89 years. Cortical thickness and surface area were extracted at each site using FreeSurfer.
CM severity was associated with reduced cortical thickness in the banks of the superior temporal sulcus and supramarginal gyrus as well as with reduced surface area of the middle temporal lobe. Participants reporting both childhood neglect and abuse had a lower cortical thickness in the inferior parietal lobe, middle temporal lobe, and precuneus compared to participants not exposed to CM. In males only, regardless of diagnosis, CM severity was associated with higher cortical thickness of the rostral anterior cingulate cortex. Finally, a significant interaction between CM and age in predicting thickness was seen across several prefrontal, temporal, and temporo-parietal regions.
Severity and type of CM may impact cortical thickness and surface area. Importantly, CM may influence age-dependent brain maturation, particularly in regions related to the default mode network, perception, and theory of mind.
Background: CNS innate immune cells, microglia and macrophages (MMs), are the largest component of the inflammatory infiltrate in glioblastoma (GBM). They initially participate in tumor surveillance, but are subverted by GBM. Immunotherapies have proven incredibly successful in cancers such as melanoma, but not against GBM in part because GBM-associated MMs are not well understood. We hypothesized the content and inflammatory phenotype of MMs in GBM is variable between patients. We suspect MMs in IDH-wildtype and –mutant GBMs display divergent inflammatory phenotypes that helps explain the latter's better prognosis. Understanding GBM-associated MM heterogeneity will allow for better immunotherapy development and selection. Methods: MMs were isolated from untreated human IDH-wildtype and -mutant GBMs using flow cytometry and cultured for collection of conditioned media and analysis of secretory products. Automated segmentation with a high-content analysis system was used to quantitate MM content and inflammatory phenotype in frozen sections. New bioinformatics techniques allowed the comparison of MM profiles in publicly available single-cell RNA-sequencing databases with IDH-wildtype and -mutant GBMs. Results: Surprisingly marked variation in MM content exists between GBMs ranging from ~0-70%. A mixture of pro- and anti-inflammatory MMs are found in each GBM. Interestingly, IDH-mutant GBM-associated MMs were more activated than MMs in IDH-wildtype GBMs. Conclusions: Taken together, the highly variable MM content and phenotype of GBMs suggests the success of immunotherapies hinges on taking a precision medicine approach. MM-rich GBMs would benefit more from therapies that target them. MM activation in IDH-mutant GBMs may contribute to better patient prognoses.
The course of illness in obsessive–compulsive disorder (OCD) varies significantly between patients. Little is known about factors predicting a chronic course of illness. The aim of this study is to identify factors involved in inducing and in maintaining chronicity in OCD.
The present study is embedded within the Netherlands Obsessive Compulsive Disorder Association (NOCDA) study, an ongoing multicenter naturalistic cohort study designed to identify predictors of long-term course and outcome in OCD. For this study, 270 subjects with a current diagnosis of OCD were included. Chronicity status at 2-year follow-up was regressed on a selection of baseline predictors related to OCD, to comorbidity and to stress and support.
Psychotrauma [odds ratio (OR) 1.98, confidence interval (CI) 1.22–3.22, p = 0.006], recent negative life events (OR 1.42, CI 1.01–2.01, p = 0.043), and presence of a partner (OR 0.28, CI 0.09–0.85, p = 0.025) influenced the risk of becoming chronic. Longer illness duration (OR 1.46, CI 1.08–1.96, p = 0.013) and higher illness severity (OR 1.09, CI 1.03–1.16, p = 0.003) increased the risk of remaining chronic.
External influences increase the risk of becoming chronic, whereas the factors involved in maintaining chronicity are illness-related. As the latter are potentially difficult to modify, treatment should be devoted to prevent chronicity from occurring in the first place. Therapeutic strategies aimed at alleviating stress and at boosting social support might aid in achieving this goal.
What might the contemporary performing body look like when it seeks to communicate and to cultivate the need to live well within the natural environment, whether the context of that living well is framed and set upon either by long-standing cultural traditions or by diverse modernizing forces over time? The Singapore performance and visual artist Tang Da Wu has engaged with a present and a region fractured by the predations of unacceptable cultural norms – the consequences of colonial modernity or the modern nation state taking on imperial pretensions – and the subsumption of Singapore society under capitalist modernization. Tang's performing body both refuses the diminution of time to the present, as is the wont of the forces he engages with, and undertakes interventions by sometimes elusive and ironic means – unlike some overdetermined contemporary performance art – that reject the image of the modernist ‘artist as hero’. Part of the cause for this distinctive art committed to historicity and a deliberate ordinariness is that artistic communication to him means provoking self-reflexive thought rather than immediate action. Over the years this has resulted in collaborative artistic workshops, in which he has imaginatively transferred art making from his body to the realm of ordinary people. These workshops become his particular extension of the neo-avant-garde's breaching of art's infrastructures.
Feedback learning is essential for behavioral development. We investigated feedback learning in relation to behavior problems after pediatric traumatic brain injury (TBI).
Children aged 6–13 years diagnosed with TBI (n = 112; 1.7 years post-injury) were compared with children with traumatic control (TC) injury (n = 52). TBI severity was defined as mild TBI without risk factors for complicated TBI (mildRF− TBI, n = 24), mild TBI with ⩾1 risk factor for complicated TBI (mildRF+ TBI, n = 51) and moderate/severe TBI (n = 37). The Probabilistic Learning Test was used to measure feedback learning, assessing the effects of inconsistent feedback on learning and generalization of learning from the learning context to novel contexts. The relation between feedback learning and behavioral functioning rated by parents and teachers was explored.
No evidence was found for an effect of TBI on learning from inconsistent feedback, while the moderate/severe TBI group showed impaired generalization of learning from the learning context to novel contexts (p = 0.03, d = −0.51). Furthermore, the mildRF+ TBI and moderate/severe TBI groups had higher parent and teacher ratings of internalizing problems (p's ⩽ 0.04, d's ⩾ 0.47) than the TC group, while the moderate/severe TBI group also had higher parent ratings of externalizing problems (p = 0.006, d = 0.58). Importantly, poorer generalization of learning predicted higher parent ratings of externalizing problems in children with TBI (p = 0.03, β = −0.21) and had diagnostic utility for the identification of children with TBI and clinically significant externalizing behavior problems (area under the curve = 0.77, p = 0.001).
Moderate/severe pediatric TBI has a negative impact on generalization of learning, which may contribute to post-injury externalizing problems.
While the growth of pits in passive metals exposed to chloride solutions is well understood, the processes associated with the initiation and propagation of stable pits, versus pits that form and apparently re-passivate, are still a matter of conjecture. A major challenge in studying pit initiation using electron microscopy has been alteration of the structure and chemistry of the hydrated corrosion films upon transfer to the vacuum environment of the microscope. A recently developed technique uses a microfluidic liquid cell to maintain the aqueous environment in contact with the sample. This work uses such cells to directly observe pits initiating, and growing before reaching stability, in aluminum thin films under potentiostatic polarization in situ in the electron microscope. Polarization curves developed in the cell show good agreement with those observed under conventional electrochemical experimental conditions. We observed current transients representative of metastable pitting and were able to relate crystalline features found in situ with topographic features using atomic force microscopy (AFM). An accumulation of aluminum surrounding an initiated pit, combined with depth profiling using Auger electron spectroscopy suggests that aluminum metal is deposited during the pit initiation process, and may serve to reduce lateral dissolution of the aluminum film. Work is currently underway to determine if this observation is unique to the geometry of the microfluidics cell or if is a general result that occurs at the very beginning of pit initiation.
Childhood maltreatment (CM) may modify the relationship between major depressive disorder (MDD) and hippocampal volume reduction. To disentangle the impact of MDD and CM on hippocampal volume we investigated the association between MDD and hippocampal volume in persons with and without a history of CM in two independent cohorts.
We used data of 262 participants from the Netherlands Study of Depression and Anxiety (NESDA) (mean age 37 years, 32% male) and 636 participants from the SMART-Medea study (mean age 61 years, 81% male). In both studies a 12-month diagnosis of MDD and CM were assessed using a diagnostic interview. Hippocampal volume was measured in NESDA using FreeSurfer software on 3-T magnetic resonance (MR) images and in SMART it was manually outlined on 1.5-T MR images. With analysis of covariance adjusted for intracranial volume, age, gender and lifestyle factors we estimated the effects of MDD and CM on hippocampal volume.
In both cohorts CM was not significantly associated with hippocampal volume. After pooling the data MDD was associated with smaller hippocampal volume (B = −138.90 mm3, p = 0.05) and the interaction between MDD and CM reached significance (p = 0.04); in participants with CM, MDD was related to smaller hippocampal volume (NESDA: B = −316.8 mm3, p = 0.02; SMART: B = −407.6, p = 0.046), but not in participants without CM (p > 0.05).
Our study shows that in two independent cohorts, particularly in individuals with CM, a diagnosis of MDD is related to smaller hippocampal volume. Prospective studies are needed to further determine through which mechanism CM may amplify the relationship between MDD and hippocampal volume.
Data from the general population show higher prevalence of different anxiety disorders in women as compared with men. We analysed gender differences in a naturalistic sample of outpatients with anxiety disorders in a mental healthcare setting.
Routine outcome monitoring data were collected from 1333 patients (age: 18–65; 63.3% women) fulfilling Diagnostic and Statistical Manual of Mental Disorders IV criteria of current anxiety disorder according to the Mini-International Neuropsychiatric Interview between 2004 through 2006. Data included Comprehensive Psychopathological Rating Scale, Brief Symptom Inventory (BSI), Short Form Health Survey (SF-36), Mood and Anxiety Symptom Questionnaire (MASQ). Chi-squared test and t-test were used to compare women with men for variables with parametric distributions, and Mann–Whitney test for non-parametric distribution. Adjustments for potential confounders (age, level of education, ethnicity and comorbidites) were made by logistic regression models (for discrete variables) or analysis of covariance.
The female-to-male ratio (i.e., 844 women, 489 men) for any anxiety disorder was 1.73 : 1 (95% confidence interval [CI]: 1.63–1.83), with the strongest skewness for post-traumatic stress disorder (2.80 : 1) and the smallest one for social phobia (1.18 : 1). Compared with men, women reported more severe self-rating scores on the BSI (on average, the scores were 12.3% higher on 3 of 9 subscales: somatisation, interpersonal sensitivity and anxiety), SF-36 (self-reported generic health status was lower on 5 of 8 subscales: physical functioning, social functioning, physical problems, vitality and bodily pain) and MASQ (on average, the scores were 6.6% higher on 4 of 5 subscales: anxious arousal, general distress, general distress depression, general distress anxiety). On the contrary, no gender difference was found in the severity of anxiety symptoms measured by the Brief Anxiety Scale. Women were more likely to suffer from comorbid depression and bulimia nervosa, and less likely from substance abuse.
In a treatment-seeking population the prevalence rate of anxiety disorders was 1.7 times higher in female compared with men. Female outpatients were more severely affected on self-rated but not on observer-rated scales.
In this paper we present a probabilistic fast model for performance assessment of geothermal doublets for direct heat applications. It is a simple yet versatile and multipurpose tool. It can be well applied in better understanding the sensitivity of performance to key subsurface parameters and depth trends therein, and for assessing the probability of success for geothermal projects under technical and financial constraints.
The underlying algorithms deliver a sensible accuracy given the uncertainties associated with geothermal projects at exploration state. A public release of the software, available under the name of DoubletCalc, is easy to handle and requires a limited set of input parameters. Thanks to an open source code, DoubletCalc can be implemented in other software applications and extended as it has been implemented for the integration into the national geothermal information system in the Netherlands (ThermoGIS, 2011).
Apart from its application for site assessments, the tool can be integrated into automated workflows processing faster representations of key aquifer properties and capable to produce indicative maps for predicted doublet power, economic feasibility and prediction of cumulative amount of heat that can be recovered. These capabilities are specifically important for decision support for policymakers while assessing the effects of particular insurance schemes and funding mechanisms.
DoubletCalc cannot and is not intended to substitute geologic exploration approaches. As exploration measures, such as seismic surveys are cost intensive, DoubletCalc can be used to focus geothermal exploration on areas and sites where an enhanced probability of success can be expected.
Subsurface temperature is a key parameter for geothermal energy prospection in sedimentary basins. Here, we present the results of a 3D temperature modelling using a thermal-tectonic forward modelling method, calibrated with subsurface temperature measurements in the Netherlands. The first step involves the generation of a coherent dataset of temperature values for the calibration of the model. In the Netherlands, most of the available measurements (98.8%) are BHT measurements and therefore need to be corrected from the thermal perturbation created during drilling. The remaining 1.2% is composed of DST measurements, which closely resemble the formation temperature (i.e., ±5 °C). The resulting dataset, after correction, gives a total number of 1293 values in 454 wells. Included in this dataset are 412 highly reliable values corrected with the Instantaneous Cylinder Source (ICS) method and 829 values of a lower reliability corrected with the AAPG method. In addition to the corrected values, 52 DST values in 26 wells are available from the Dutch subsurface. The average thermal gradient of this whole dataset is 31.3 °C/km with a surface temperature of 10.1 °C. The second step in the modelling process was the generation of a 3D forward model that focuses on calculating the temperature distribution of the sedimentary basin fill, taking into account the basin evolution of the past 20 Myrs and thermal properties and processes of the whole lithosphere. From the 3D thermal model, we extracted 2D cross sections across well locations to compare model temperatures with calibration data. Furthermore, we present vertical profiles, isodepth maps and temperature projection on geological layers, to discuss the relationship between temperature and geology. Anomalies in this relationship can have several causes and include: 1) the extreme thermal conductivity and complex geometry of the Zechstein salt; 2) enhanced radiogenic heat production of the upper crust due to magmatic intrusions. In addition, our model supports earlier findings that shallow hydrothermal convection in highly permeable sediments can effectively lower thermal conductivity and temperatures in shallow sediments.
A resource assessment methodology has been developed to designate prospective high permeable clastic aquifers and to assess the amount of potential geothermal energy in the Netherlands. It builds from the wealth of deep subsurface data from oil and gas exploration and production which is publicly and digitally available. In the resource assessment various performance indicator maps have been produced for direct heat applications (greenhouse and spatial heating). These maps are based on detailed mapping of depth, thickness, porosity, permeability, temperature and transmissivity (methodology presented in other papers in this NJG issue). In the resource assessment analysis 14 lithostratigraphic units (clastic aquifers) have been considered, ranging in age from the Permian to the Cenozoic. Performance maps have been made which include a) the expected doublet power (MWth) to be retrieved; b) the number of houses or hectares that can be heated from one doublet; and c) a potential indicator map, which provides insight in subsurface suitability for specific applications from a techno-economic perspective. To obtain a nationwide overview of the resource potential in terms of recoverable geothermal energy, a progressive filtering approach was used from total heat content of the reservoirs (Heat In Place – HIP) via the heat that can potentially be recovered (Potential Recovery Heat – PRH) to energy maps taking into account a techno-economic performance evaluation (Recoverable Heat – RH). Results show that the HIP is approximately 820,000 PJ which is significantly more than previous estimates of around 90,000 PJ. This considerable increase in geothermal energy potential is the result of accurate geological mapping of key reservoir properties and the development of state-of-the-art techno-economic performance assessment tools that performs Monte Carlo simulation. Moreover, for the previous estimates boundary conditions were set with the aim to compare the geothermal potential between different EU countries (Rijkers & Van Doorn, 1997). Taking into account techno-economic aspects, the RH is in the order of 85,000 PJ. This is equivalent to ~70% of the ultimate recoverable gas of the Slochteren Gas field. In total over 400 maps have been created or used as input for the resource assessment. Together, they provide comprehensive information for geothermal energy development from various stakeholder perspectives. The maps can be interactively assessed in the web-based portal ThermoGIS (www.thermogis.nl). This application complements existing subsurface information systems available in the Netherlands and supports the geothermal community in assessing the feasibility of a geothermal system on a regional scale.
Geothermal low enthalpy heat in non-magmatic areas can be produced by pumping hot water from aquifers at large depth (>1 km). Key parameters for aquifer performance are temperature, depth, thickness and permeability. Geothermal exploration in the Netherlands can benefit considerably from the wealth of oil and gas data; in many cases hydrocarbon reservoirs form the lateral equivalent of geothermal aquifers. In the past decades subsurface oil and gas data have been used to develop 3D models of the subsurface structure. These models have been used as a starting point for the mapping of geothermal reservoir geometries and its properties. A workflow was developed to map aquifer properties on a regional scale. Transmissivity maps and underlying uncertainty have been obtained for 20 geothermal aquifers. Of particular importance is to take into account corrections for maximum burial depth and the assessment of uncertainties. The mapping of transmissivity and temperature shows favorable aquifer conditions in the northern part of the Netherlands (Rotliegend aquifers), while in the western and southern parts of the Netherlands aquifers of the Triassic and Upper Cretaceous / Jurassic have high prospectivity. Despite the high transmissivity of the Cenozoic aquifers, the limited depth and temperature reduce the prospective geothermal area significantly.
The results show a considerable remaining uncertainty of transmissivity values, due to lack of data and heterogeneous spatial data distribution. In part these uncertainties may be significantly reduced by adding well test results and facies parameters for the map interpolation in future work. For underexplored areas this bears a significant risk, but it can also result in much higher flowrates than originally expected, representing an upside in project performance.
One of the fundamental challenges in understanding the early stages of corrosion pitting in metals protected with an oxide film is that there are relatively few techniques that can probe microstructure with sufficient resolution while maintaining a wet environment. Here, we demonstrate that microstructural changes in Al thin films caused by aqueous NaCl solutions of varying chloride concentrations can be directly observed using a liquid flow cell enclosed within a transmission electron microscope (TEM) holder. In the absence of chloride, Al thin films did not exhibit significant corrosion when immersed in de-ionized water for 2 days. However, introducing 0.01 M NaCl solutions led to extensive random formation of blisters over the sample surface, while 0.1 M NaCl solutions formed anomalous structures that were larger than the typical grain size. Immersion in 1.0 M NaCl solutions led to fractal corrosion consistent with previously reported studies of Al thin films using optical microscopy. These results show the potential of in situ liquid cell electron microscopy for probing the processes that take place before the onset of pitting and for correlating pit locations with the underlying microstructure of the material.
The materials class of skutterudites is one of the promising thermoelectric materials due to its decent electronic properties and cage-like structural feature that can be filled with guest atoms. First principles calculations have been performed in order to investigate electronic band structures and related transport properties of pnictogen-substitued skutterudites filled with alkaline-earth elements (MxCo4A6Te6 where M=Ca, Sr, or Ba, A=Ge or Sn, and x=0.5 or 1). The Seebeck coefficient and the power factor, which are electronic transport properties related to thermoelectricity, are computed by using the Boltzmann transport formalism within the constant-relaxation-time-approximation. The results are compared against the corresponding properties of the unfilled pnictogen-substitued ternary skutterudites (CoA1.5Te1.5) to identify the effects of filling, based on which the potential of filled pnictogen-substituted skutterudites for thermoelectric applications is evaluated. The possible changes in the ionic character of the interatomic bonding, which was suspected to be an important scattering source, are probed by analyzing the projected density of states.
Depressive disorders are highly prevalent in adolescence and confer a heightened risk of recurrence in adulthood. Insight into the developmental neurocircuitry of depression could advance our understanding of depression and aid the development of effective treatment strategies. Whereas white-matter (WM) abnormalities are strongly implicated in adult depression, we still lack a firm understanding of WM architecture in adolescent depression. Using diffusion tensor imaging (DTI), we set out to investigate WM microstructure in a sample of clinically depressed adolescents relative to matched controls.
We employed tract-based spatial statistics (TBSS) to examine WM microstructure in 25 treatment-naive adolescents with clinical depression relative to 21 matched controls. Using TBSS, we examined fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD). Threshold-free cluster enhancement (TFCE) with family-wise error (FWE) correction was used to control for multiple comparisons.
Our analysis revealed abnormal WM microstructure in clinically depressed adolescents. More specifically, whole-brain analysis revealed that patients had lower FA values in the body of the corpus callosum (CC), coupled with elevated RD and MD, and preserved AD. Conversely, region-of-interest analysis revealed that patients had higher FA values in the uncinate fasciculus (UF), coupled with elevated AD, reduced RD and preserved MD.
In line with neurocircuitry models of depression, our findings suggest that WM abnormalities within pathways facilitating cognitive and emotional functioning are involved in the pathophysiology of depression. Importantly, our findings show that these WM abnormalities are already present early in the course of the disorder.
Patient registries represent an important method of organizing “real world” patient information for clinical and research purposes. Registries can facilitate clinical trial planning and recruitment and are particularly useful in this regard for uncommon and rare diseases. Neuromuscular diseases (NMDs) are individually rare but in aggregate have a significant prevalence. In Canada, information on NMDs is lacking. Barriers to performing Canadian multicentre NMD research exist which can be overcome by a comprehensive and collaborative NMD registry.
We describe the objectives, design, feasibility and initial recruitment results for the Canadian Neuromuscular Disease Registry (CNDR).
The CNDR is a clinic-based registry which launched nationally in June 2011, incorporates paediatric and adult neuromuscular clinics in British Columbia, Alberta, Ontario, Quebec, New Brunswick and Nova Scotia and, as of December 2012, has recruited 1161 patients from 12 provinces and territories. Complete medical datasets have been captured on 460 “index disease” patients. Another 618 “non-index” patients have been recruited with capture of physician-confirmed diagnosis and contact information. We have demonstrated the feasibility of blended clinic and central office-based recruitment. “Index disease” patients recruited at the time of writing include 253 with Duchenne and Becker muscular dystrophy, 161 with myotonic dystrophy, and 71 with ALS.
The CNDR is a new nationwide registry of patients with NMDs that represents an important advance in Canadian neuromuscular disease research capacity. It provides an innovative platform for organizing patient information to facilitate clinical research and to expedite translation of recent laboratory findings into human studies.
Research into age of onset in obsessive–compulsive disorder (OCD) has indicated significant differences between patients with early and late onset of the disorder. However, multiple criteria have been used arbitrarily for differentiating between early- and late-onset OCD, rendering inconsistent results that are difficult to interpret.
In the current study, admixture analysis was conducted in a sample of 377 OC patients to determine the number of underlying populations of age of onset and associated demographic and clinical characteristics. Various measures of anxiety, depression, co-morbidity, autism, OCD, tics and attention deficit hyperactivity disorder (ADHD) symptoms were administered.
A bimodal age of onset was established and the best-fitting cut-off score between early and late age of onset was 20 years (early age of onset ⩽19 years). Patients with early age of onset were more likely to be single. Early age of onset patients demonstrated higher levels of OCD severity and increased symptoms on all OCD dimensions along with increased ADHD symptoms and higher rates of bipolar disorder.
It is suggested that 20 years is the recommended cut-off age for the determination of early versus late age of onset in OCD. Early age of onset is associated with a generally graver OCD clinical picture and increased ADHD symptoms and bipolar disorder rates, which may be related to greater functional implications of the disorder. We propose that age of onset could be an important marker for the subtyping of OCD.
Amyotrophic lateral sclerosis (ALS) is a devastating cause of progressive weakness, respiratory failure and death. To date there is no effective therapy to meaningfully extend survival but continuously emerging targets and putative treatments are studied in clinical trials. Canadian epidemiological data on ALS is scarce and the socioeconomic impact of ALS on Canadian society is unclear. The Canadian Neuromuscular Disease Registry (CNDR) is a national clinic-based registry of patients with neuromuscular diseases with the goal of facilitating the design and execution of clinical research.
We conducted a national stakeholder survey to assess interest for a Canadian ALS registry and an assessment of expected case ascertainment. A dataset derivation meeting was held to establish the registry medical dataset.
We report the results of the national stakeholder survey, case ascertainment assessment, and the derived dataset that have resulted in the current implementation of a Canadian registry of patients with ALS.
The development of this long sought-after resource is a significant step forward for the Canadian ALS patient and research communities that will result in more efficient clinical trial recruitment and advancements in our understanding of ALS in Canada.