Examining concurrent validity and item selection of the Session Wants and Needs Outcome Measure (SWAN-OM) in a children and young people web-based therapy service.

Background: Single-session mental health interventions are frequently attended by children and young people (CYP) in both web-based and face-to-face therapy settings. The Session "Wants" and "Needs" Outcome Measure (SWAN-OM) is an instrument developed in a web-based therapy service to overcome the challenges of collecting outcomes and experiences of single-session therapies (SSTs). It provides pre-defined goals for the session, selected by the young person prior to the intervention, on which progress toward achievement is scored at the end of the session. Objective: The objective of this study was to evaluate the instrument's psychometric properties, including concurrent validity against three other frequently used outcome and experience measures, at a web-based and text-based mental health service. Methods: The SWAN-OM was administered for a period of 6 months to 1,401 CYP (aged 10-32 years; 79.3% white; 77.59% female) accessing SST on a web-based service. Item correlations with comparator measures and hierarchical logistic regressions to predict item selection were calculated for concurrent validity and psychometric exploration. Results: The most frequently selected items were "Feel better" (N = 431; 11.61%) and "Find ways I can help myself" (N = 411; 11.07%); unpopular items were "Feel safe in my relationships" (N = 53; 1.43%) and "Learn the steps to achieve something I want" (N = 58; 1.56%). The SWAN-OM was significantly correlated with the Experience of Service Questionnaire, particularly the item "Feel better" [rs(109) = 0.48, p < 0.001], the Youth Counseling Impact Scale, particularly the item "Learn the steps to achieve something I want" [rs(22) = 0.76, p < 0.001], and the Positive and Negative Affect Schedule, particularly the items "Learn how to feel better" [rs(22) = 0.72, p < 0.001] and "Explore how I feel" [rs(70) = -0.44, p < 0.001]. Conclusion: The SWAN-OM demonstrates good concurrent validity with common measures of outcome and experience. Analysis suggests that lesser-endorsed items may be removed in future iterations of the measure to improve functionality. Future research is required to explore SWAN-OM's potential to measure meaningful change in a range of therapeutic settings.

Clinical and molecular analysis in Papillon-Lefèvre syndrome.

Papillon-Lefèvre syndrome (PLS; MIM#245000) is a rare recessive autosomal disorder characterized by palmar and plantar hyperkeratosis, and aggressively progressing periodontitis leading to premature loss of deciduous and permanent teeth. PLS is caused by loss-of-function mutations in the CTSC gene, which encodes cathepsin C. PLS clinical expressivity is highly variable and no consistent genotype-phenotype correlation has been demonstrated yet. Here we report the clinical and genetic features of five PLS patients presenting a severe periodontal breakdown in primary and permanent dentition, hyperkeratosis over palms and soles, and recurrent sinusitis and/or tonsillitis. Mutation analysis revealed two novel homozygous recessive mutations (c.947T>C and c.1010G>C) and one previous described homozygous recessive mutation (c.901G>A), with parents carrying them in heterozygous, in three families (four patients). The fourth family presented with the CTSC c.628C>T mutation in heterozygous, which was inherited maternally. Patient carrying the CTSC c.628C>T mutation featured classical PLS phenotype, but no PLS clinical characteristics were found in his carrier mother. All mutations were found to affect directly (c.901G>A, c.947T>C, and c.1010G>C) or indirectly (c.628C>T, which induces a premature termination) the heavy chain of the cathepsin C, the region responsible for activation of the lysosomal protease. Together, these findings indicate that both homozygous and heterozygous mutations in the cathepsin C heavy chain domain may lead to classical PLS phenotype, suggesting roles for epistasis or gene-environment interactions on determination of PLS phenotypes.

A high resolution 7-Tesla resting-state fMRI test-retest dataset with cognitive and physiological measures.

Here we present a test-retest dataset of functional magnetic resonance imaging (fMRI) data acquired at rest. 22 participants were scanned during two sessions spaced one week apart. Each session includes two 1.5 mm isotropic whole-brain scans and one 0.75 mm isotropic scan of the prefrontal cortex, giving a total of six time-points. Additionally, the dataset includes measures of mood, sustained attention, blood pressure, respiration, pulse, and the content of self-generated thoughts (mind wandering). This data enables the investigation of sources of both intra- and inter-session variability not only limited to physiological changes, but also including alterations in cognitive and affective states, at high spatial resolution. The dataset is accompanied by a detailed experimental protocol and source code of all stimuli used.

Medial prefrontal and anterior cingulate cortical thickness predicts shared individual differences in self-generated thought and temporal discounting.

When deprived of compelling perceptual input, the mind is often occupied with thoughts unrelated to the immediate environment. Previous behavioral research has shown that this self-generated task-unrelated thought (TUT), especially under non-demanding conditions, relates to cognitive capacities such as creativity, planning, and reduced temporal discounting. Despite the frequency and importance of this type of cognition, little is known about its structural brain basis. Using MRI-based cortical thickness measures in 37 participants, we were able to show that individuals with a higher tendency to engage in TUT under low-demanding conditions (but not under high-demanding conditions) show an increased thickness of medial prefrontal cortex (mPFC) and anterior/midcingulate cortex. Thickness of these regions also related to less temporal discounting (TD) of monetary rewards in an economic task, indicative of more patient decision-making. The findings of a shared structural substrate in mPFC and anterior/midcingulate cortex underlying both TUT and TD suggest an important role of these brain regions in supporting the self-generation of information that is unrelated to the immediate environment and which may be adaptive in nature.

How self-generated thought shapes mood--the relation between mind-wandering and mood depends on the socio-temporal content of thoughts.

Recent work has highlighted that the generation of thoughts unrelated to the current environment may be both a cause and a consequence of unhappiness. The current study used lag analysis to examine whether the relationship between self-generated thought and negative affect depends on the content of the thoughts themselves. We found that the emotional content could strongly predict subsequent mood (e.g. negative thoughts were associated with subsequent negative mood). However, this direct relationship was modulated by the socio-temporal content of the thoughts: thoughts that were past- and other-related were associated with subsequent negative mood, even if current thought content was positive. By contrast, future- and self-related thoughts preceded improvements of mood, even when current thought content was negative. These results highlight the important link between self-generated thought and mood and suggest that the socio-temporal content plays an important role in determining whether an individual's future affective state will be happy or sad.

The default modes of reading: modulation of posterior cingulate and medial prefrontal cortex connectivity associated with comprehension and task focus while reading.

Reading is a fundamental human capacity and yet it can easily be derailed by the simple act of mind-wandering. A large-scale brain network, referred to as the default mode network (DMN), has been shown to be involved in both mind-wandering and reading, raising the question as to how the same neural system could be implicated in processes with both costs and benefits to narrative comprehension. Resting-state functional magnetic resonance imaging (rs-fMRI) was used to explore whether the intrinsic functional connectivity of the two key midline hubs of the DMN-the posterior cingulate cortex (PCC) and anterior medial prefrontal cortex (aMPFC)-was predictive of individual differences in reading comprehension and task focus recorded outside of the scanner. Worse comprehension was associated with greater functional connectivity between the PCC and a region of the ventral striatum. Better comprehension was associated with greater functional connectivity with a region of the right insula. By contrast reports of increasing task focus were associated with functional connectivity from the aMPFC to clusters in the PCC, the left parietal and temporal cortex, and the cerebellum. Our results suggest that the DMN has both costs (such as poor comprehension) and benefits to reading (such as an on-task focus) because its midline core can couple its activity with other regions to form distinct functional communities that allow seemingly opposing mental states to occur. This flexible coupling allows the DMN to participate in cognitive states that complement the act of reading as well as others that do not.

Letting go of the present: mind-wandering is associated with reduced delay discounting.

The capacity to self-generate mental content that is unrelated to the current environment is a fundamental characteristic of the mind, and the current experiment explored how this experience is related to the decisions that people make in daily life. We examined how task-unrelated thought (TUT) varies with the length of time participants are willing to wait for an economic reward, as measured using an inter-temporal discounting task. When participants performed a task requiring minimal attention, the greater the amount of time spent engaged in TUT the longer the individual was prepared to wait for an economic reward. These data indicate that self-generated thought engages processes associated with the successful management of long-term goals. Although immersion in the here and now is undeniably advantageous, under appropriate conditions the capacity to let go of the present and consider more pertinent personal goals may have its own rewards.

Is self-generated thought a means of social problem solving?

Appropriate social problem solving constitutes a critical skill for individuals and may rely on processes important for self-generated thought (SGT). The aim of the current study was to investigate the link between SGT and social problem solving. Using the Means-End Problem Solving task (MEPS), we assessed participants' abilities to resolve daily social problems in terms of overall efficiency and number of relevant means they provided to reach the given solution. Participants also performed a non-demanding choice reaction time task (CRT) and a moderately-demanding working memory task (WM) as a context in which to measure their SGT (assessed via thought sampling). We found that although overall SGT was associated with lower MEPS efficiency, it was also associated with higher relevant means, perhaps because both depend on the capacity to generate cognition that is independent from the hear and now. The specific content of SGT did not differentially predict individual differences in social problem solving, suggesting that the relationship may depend on SGT regardless of its content. In addition, we also found that performance at the WM but not the CRT was linked to overall better MEPS performance, suggesting that individuals good at social processing are also distinguished by their capacity to constrain attention to an external task. Our results provide novel evidence that the capacity for SGT is implicated in the process by which solutions to social problems are generated, although optimal problem solving may be achieved by individuals who display a suitable balance between SGT and cognition derived from perceptual input.

Phase II screening trial of lithium carbonate in amyotrophic lateral sclerosis: examining a more efficient trial design.

OBJECTIVE: To use a historical placebo control design to determine whether lithium carbonate slows progression of amyotrophic lateral sclerosis (ALS). METHODS: A phase II trial was conducted at 10 sites in the Western ALS Study Group using similar dosages (300-450 mg/day), target blood levels (0.3-0.8 mEq/L), outcome measures, and trial duration (13 months) as the positive trial. However, taking riluzole was not a requirement for study entry. Placebo outcomes in patients matched for baseline features from a large database of recent clinical trials, showing stable rates of decline over the past 9 years, were used as historical controls. RESULTS: The mean rate of decline of the ALS Functional Rating Scale-Revised was greater in 107 patients taking lithium carbonate (-1.20/month, 95% confidence interval [CI] -1.41 to -0.98) than that in 249 control patients (-1.01/month, 95% CI -1.11 to -0.92, p = 0.04). There were no differences in secondary outcome measures (forced vital capacity, time to failure, and quality of life), but there were more adverse events in the treated group. CONCLUSIONS: The lack of therapeutic benefit and safety concerns, taken together with similar results from 2 other recent trials, weighs against the use of lithium carbonate in patients with ALS. The absence of drift over time and the availability of a large database of patients for selecting a matched historical control group suggest that use of historical controls may result in more efficient phase II trials for screening putative ALS therapeutic agents. CLASSIFICATION OF EVIDENCE: This study provided Class IV evidence that lithium carbonate does not slow the rate of decline of function in patients with ALS over 13 months.

Therapeutic exercise for people with amyotrophic lateral sclerosis or motor neuron disease.

BACKGROUND: Despite the high incidence of muscle weakness in individuals with amyotrophic lateral sclerosis (ALS) or motor neuron disease (MND), the effects of exercise in this population are not well understood. OBJECTIVES: The objective was to systematically review randomised and quasi-randomised studies of exercise for people with ALS or MND. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group Trials Register, EMBASE (January 1980 to August 2007), LILACS (January 1982 to August 2007), MEDLINE (January 1966 to August 2007), Cochrane Central Register of Controlled Trials (CENTRAL), PEDro (January 1980 to August 2007), AMED (January 1985 to August 2007), HealthSTAR (January 1975 to August 2007), CINAHL (January 1982 to August 2007). We also searched Dissertation Abstracts, inspected the reference lists of all papers selected for review and contacted the authors with expertise in the field. SELECTION CRITERIA: We included randomised or quasi-randomised controlled trials of people with a diagnosis of definite, probable, probable with laboratory support, or possible amyotrophic lateral sclerosis, as defined by the El Escorial criteria. We included progressive resistance or strengthening exercise and endurance or aerobic exercise. The control condition was no exercise or standard rehabilitation management. Our primary outcome measure was improvement in functional ability, decrease in disability or reduction in rate of decline as measured by a validated outcome tool at three months. Our secondary outcome measures were improvement in psychological status or quality of life, decrease in fatigue, increase in, or reduction in rate of decline of muscle strength (strengthening or resistance studies), increase in, or reduction in rate of decline of aerobic endurance (aerobic or endurance studies) at three months and frequency of adverse effects. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted the data. The authors of the papers were contacted to obtain information not available in the published articles. MAIN RESULTS: We identified two randomised controlled trials that met our inclusion criteria. The first examined the effects of a twice-daily exercise program of moderate load, endurance exercise versus "usual activities" in 25 people with ALS. The second examined the effects of thrice weekly moderate load and moderate intensity resistance exercises compared to usual care (stretching exercises) in 27 people with ALS. After three months, when the results of the two trials were combined, there was a significant weighted mean improvement in the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS) measure of function in the exercise compared with the control groups (3.21, 95% confidence interval 0.46 to 5.96) in favour of the exercise group. No statistically significant differences in quality of life, fatigue or muscle strength were found. AUTHORS' CONCLUSIONS: The only studies detected were too small to determine to what extent strengthening exercises for people with ALS are beneficial, or whether exercise is harmful. There is a complete lack of randomised or quasi-randomised clinical trials examining aerobic exercise in this population. More research is needed.

A randomized controlled trial of resistance exercise in individuals with ALS.

OBJECTIVE: To determine the effects of resistance exercise on function, fatigue, and quality of life in individuals with ALS. METHODS: Subjects with a diagnosis of clinically definite, probable, or laboratory-supported ALS, forced vital capacity (FVC) of 90% predicted or greater, and an ALS Functional Rating Scale (ALSFRS) score of 30 or greater were randomly assigned to a resistance exercise group that received a home exercise program consisting of daily stretching and resistance exercises three times weekly or to a usual care group, who performed only the daily stretching exercises. ALSFRS, the Fatigue Severity Scale (FSS), and Short Form-36 (SF-36) were completed at baseline and monthly for 6 months. FVC and maximum voluntary isometric contraction (MVIC) were monitored monthly throughout the study. RESULTS: Of 33 subjects screened, 27 were randomly assigned (resistance = 13; usual care = 14). Eight resistance exercise subjects and 10 usual care subjects completed the trial. At 6 months, the resistance exercise group had significantly higher ALSFRS and SF-36 physical function subscale scores. No adverse events related to the intervention occurred, MVIC and FVC indicated no negative effects, and less decline in leg strength measured by MVIC was found in the resistance exercise group. CONCLUSION: Our study, although small, showed that the resistance exercise group had significantly better function, as measured by total ALS Functional Rating Scale and upper and lower extremity subscale scores, and quality of life without adverse effects as compared with subjects receiving usual care.

Intrarater reliability of manual muscle test (Medical Research Council scale) grades in Duchenne's muscular dystrophy.

The purpose of this study was to document the intrarater reliability of manual muscle test (MMT) grades in assessing muscle strength in patients with Duchenne's muscular dystrophy (DMD). Subjects were 102 boys, aged 5 to 15 years, who were participating in a double-blind, multicenter trial to document the effects of prednisone on muscle strength in patients with DMD. Four physical therapists participated in the study. Two identical (duplicate) evaluations were performed within 5 days of each other by the same examiner initially and after 6 and 12 months of treatment. A total of 18 muscle groups were tested on each patient, 16 of them bilaterally, using a modification of the Medical Research Council scale. Reliability of muscle strength grades obtained for individual muscle groups and of individual muscle strength grades was analyzed using Cohen's weighted Kappa. The reliability of grades for individual muscle groups ranged from .65 to .93, with the proximal muscles having the higher reliability values. The reliability of individual muscle strength grades ranged from .80 to .99, with those in the gravity-eliminated range scoring the highest. We conclude the MMT grades are reliable for assessing muscle strength in boys with DMD when consecutive evaluations are performed by the same physical therapist.

Long-term benefit from prednisone therapy in Duchenne muscular dystrophy.

Two successive, 6-month, randomized, double-blind, controlled trials of prednisone showed that 0.75 mg/kg/d was the optimal dose to improve strength in boys with Duchenne muscular dystrophy (DMD). We attempted to maintain 93 boys on that dose for an additional 2 years. During the 3 years of observation, the decline in average muscle strength scores of all boys taking prednisone was 0.072 units/yr, as compared with an expected decline of 0.341 units/yr from natural history controls. The occurrence of side effects in some boys prevented maintenance of the full dose, which may have lessened the response. At the time of last visit, dosages ranged from 0.15 mg/kg to 0.75 mg/kg. In addition to maintaining their strength, several of the boys actually improved their performance in lifting kilogram weights and in some timed function tests. Treatment of DMD with prednisone significantly slows the progression of weakness and loss of function for at least 3 years.

Randomized controlled trial of testosterone in myotonic dystrophy.

Because testosterone has an anabolic effect in myotonic dystrophy, we conducted a 12-month, randomized, double-blind therapeutic trial of testosterone enanthate (3 mg/kg/wk) in 40 men with myotonic dystrophy. We evaluated strength by manual muscle tests, quantitative myometry, pulmonary function, and quantitative functional assessment. A sustained, significant elevation of testosterone levels was produced but there was no effect on any measurement of muscle strength. Muscle mass as estimated by creatinine excretion and lean body mass (40K method) increased significantly. We conclude that testosterone does not improve strength in myotonic dystrophy despite increasing muscle mass.

Joint-transform correlator systems using deformable-mirror spatial light modulators.

Two joint-transform correlator systems based on deformable-mirror-device (DMD) spatial light modulators and charge-coupled-device (CCD) video cameras are described. The system designs provide for real-time correlation between video-formatted input scenes and stored reference images. The DMD light modulators are used exclusively for inputting data in the optical stages of these systems, and the CCD cameras are used to provide the critical square-law detection required in joint-transform architectures. Experimental verification of the functionality of these DMD/CCD joint-transform systems is also presented.

Deformable mirror device spatial light modulators and their applicability to optical neural networks.

All neural networks are characterized by a large number of interconnections between processor nodes. In general, the value of these interconnections (weights) must be modifiable. However, current semiconductor technology does not lend itself well to modifiable interconnection technology. A novel type of spatial light modulator, the deformable mirror device, is proposed as the breakthrough needed to solve the neural network interconnect problem.

Clinical investigation of Duchenne muscular dystrophy. Interesting results in a trial of prednisone.

We investigated the effect of high-dose prednisone therapy in 33 boys with Duchenne muscular dystrophy. The drug was given daily in doses of 1.5 mg/kg of body weight (to a maximum of 80 mg) for six months. Muscle strength, joint contractures, timed functional tests, functional ability, and pulmonary function were measured at the beginning and end of the treatment period. The trial was designed using natural history controls, and the power of the study was 0.80 to detect a slowing of 50% in the rate of progression. During the period of the trial, muscle strength, functional grades, timed functional tests, and pulmonary function improved. Contractures followed the expected natural history of the illness.

Controlled trial of thyrotropin releasing hormone in amyotrophic lateral sclerosis.

A double-blind controlled trial of thyrotropin releasing hormone (TRH) 150 mg IM daily in 30 patients with amyotrophic lateral sclerosis is reported. The drug/placebo was administered for 2 months, followed by a 2-month "wash-out". Evaluation of strength, functional ability, and respiratory functions was performed. A temporary increase in the strength of some muscles was detected following the administration of TRH, but no change in functional performance was noted. Neither the patients nor the investigators believed the effects were of any marked clinical significance. The course of the illness was not altered.

Reliability of goniometric measurements in patients with Duchenne muscular dystrophy.

Previous studies of reliability of goniometric measurements have produced varied findings suggesting the need to document further the reliability of measuring range of motion in different patient groups. The purpose of this study was to determine the intratester and intertester reliability of goniometric measurements of seven common upper and lower extremity joint limitations in children with Duchenne muscular dystrophy. Five physical therapists participated in the study. The procedure and order of measurements were standardized. Results showed that intratester reliability for all measurements was high (ICC = .81 to .94), but intertester reliability showed a wide variation (ICC = .25 to .91). The results of this study indicate the need to use the same examiner for long-term follow-up and for assessing results of specific treatment interventions.