Search

Multiple system atrophy (MSA) is a fatal neurodegenerative disease of unknown etiology characterized by widespread aggregation of the protein alpha-synuclein in neurons and glia. Its orphan status, biological relationship to Parkinson’s disease (PD), and rapid progression have sparked interest in drug development. One significant obstacle to therapeutics is disease heterogeneity. Here, we share our process of developing a clinical trial-ready cohort of MSA patients (69 patients in 2 years) within an outpatient clinical setting, and recruiting 20 of these patients into a longitudinal “n-of-few” clinical trial paradigm. First, we deeply phenotype our patients with clinical scales (UMSARS, BARS, MoCA, NMSS, and UPSIT) and tests designed to establish early differential diagnosis (including volumetric MRI, FDG-PET, MIBG scan, polysomnography, genetic testing, autonomic function tests, skin biopsy) or disease activity (PBR06-TSPO). Second, we longitudinally collect biospecimens (blood, CSF, stool) and clinical, biometric, and imaging data to generate antecedent disease-progression scores. Third, in our Mass General Brigham SCiN study (stemcellsinneurodegeneration), we generate induced pluripotent stem cell (iPSC) models from our patients, matched to biospecimens, including postmortem brain. We present 38 iPSC lines derived from MSA patients and relevant disease controls (spinocerebellar ataxia and PD, including alpha-synuclein triplication cases), 22 matched to whole-genome sequenced postmortem brain. iPSC models may facilitate matching patients to appropriate therapies, particularly in heterogeneous diseases for which patient-specific biology may elude animal models. We anticipate that deeply phenotyped and genotyped patient cohorts matched to cellular models will increase the likelihood of success in clinical trials for MSA.

ObjectiveTo test the relationship between clinically relevant types of GBA mutations (none, risk variants, mild mutations, severe mutations) and β-glucocerebrosidase activity in patients with Parkinson disease (PD) in cross-sectional and longitudinal case-control studies.MethodsA total of 481 participants from the Harvard Biomarkers Study (HBS) and the NIH Parkinson's Disease Biomarkers Program (PDBP) were analyzed, including 47 patients with PD carrying GBA variants (GBA-PD), 247 without a GBA variant (idiopathic PD), and 187 healthy controls. Longitudinal analysis comprised 195 participants with 548 longitudinal measurements over a median follow-up period of 2.0 years (interquartile range, 1–2 years).Resultsβ-Glucocerebrosidase activity was low in blood of patients with GBA-PD compared to healthy controls and patients with idiopathic PD, respectively, in HBS (p < 0.001) and PDBP (p < 0.05) in multivariate analyses adjusting for age, sex, blood storage time, and batch. Enzyme activity in patients with idiopathic PD was unchanged. Innovative enzymatic quantitative trait locus (xQTL) analysis revealed a negative linear association between residual β-glucocerebrosidase activity and mutation type with p < 0.0001. For each increment in the severity of mutation type, a reduction of mean β-glucocerebrosidase activity by 0.85 μmol/L/h (95% confidence interval, −1.17, −0.54) was predicted. In a first longitudinal analysis, increasing mutation severity types were prospectively associated with steeper declines in β-glucocerebrosidase activity during a median 2 years of follow-up (p = 0.02).ConclusionsResidual activity of the β-glucocerebrosidase enzyme measured in blood inversely correlates with clinical severity types of GBA mutations in PD. β-Glucocerebrosidase activity is a quantitative endophenotype that can be monitored noninvasively and targeted therapeutically.

Two purines, caffeine and urate, have been associated with a reduced risk of idiopathic Parkinson's disease (PD) in multiple cohorts and populations. The Harvard Biomarkers Study (HBS) is a longitudinal study designed to accelerate the discovery and validation of molecular diagnostic and progression markers of early-stage PD. To investigate whether these 'reduced risk' factors are associated with PD within this cohort, we conducted a cross-sectional, case-control study in 566 subjects consisting of idiopathic PD patients and healthy controls. Caffeine intake as assessed by a validated questionnaire was significantly lower in idiopathic PD patients compared to healthy controls in males (mean difference -125 mg/day, p < 0.001) but not in females (mean difference -30 mg/day, p = 0.29). A strong inverse association was also observed with plasma urate levels both in males (mean difference -0.46 mg/dL, p = 0.017) and females (mean difference -0.45 mg/dL, p = 0.001). Both analyses stratified for sex and adjusted for age, body mass index, and either urate level or caffeine consumption, respectively. These results highlight the robustness of caffeine intake and urate as factors inversely associated with idiopathic PD.

Parkinson's disease is a progressive neurodegenerative disease characterized by tremor and bradykinesia and is a common neurologic ailment. Male sex and advancing age are independent risk factors and, as the population ages, is taking an increasing toll on productivity and medical resources. There are a number of other extrapyramidal conditions that can make the diagnosis challenging. Unlike other neurodegenerative diseases, idiopathic Parkinson's disease has effective treatments that mitigate symptoms. Medications can improve day-to-day function and, in cases where medication does not give a sustained benefit or has significant side effects, treatments like deep brain stimulation result in improved quality of life.

A key driver of patients' well-being and clinical trials for Parkinson's disease (PD) is the course that the disease takes over time (progression and prognosis). To assess how genetic variation influences the progression of PD over time to dementia, a major determinant for quality of life, we performed a longitudinal genome-wide survival study of 11.2 million variants in 3,821 patients with PD over 31,053 visits. We discover RIMS2 as a progression locus and confirm this in a replicate population (hazard ratio (HR) = 4.77, P = 2.78 x 10(-11)), identify suggestive evidence for TMEM108 (HR = 2.86, P = 2.09 x 10(-8)) and WWOX (HR = 2.12, P = 2.37 x 10(-8)) as progression loci, and confirm associations for GBA (HR = 1.93, P = 0.0002) and APOE (HR = 1.48, P = 0.001). Polygenic progression scores exhibit a substantial aggregate association with dementia risk, while polygenic susceptibility scores are not predictive. This study identifies a novel synaptic locus and polygenic score for cognitive disease progression in PD and proposes diverging genetic architectures of progression and susceptibility.A genome-wide survival study identifies variants at RIMS2 associated with progression of Parkinson's disease to dementia and highlights divergence in the genetic architecture of disease onset and progression.

OBJECTIVE Deep brain stimulation (DBS) is traditionally performed on an awake patient with intraoperative recordings and test stimulation. DBS performed under general anesthesia with intraoperative MRI (iMRI) has demonstrated high target accuracy, reduced operative time, direct confirmation of target placement, and the ability to place electrodes without cessation of medications. The authors describe their initial experience with using iMRI to perform asleep DBS and discuss the procedural and radiological outcomes of this procedure. METHODS All DBS electrodes were implanted under general anesthesia by a single surgeon by using a neuronavigation system with 3-T iMRI guidance. Clinical outcomes, operative duration, complications, and accuracy were retrospectively analyzed. RESULTS In total, 103 patients treated from 2015 to 2019 were included, and all but 1 patient underwent bilateral implantation. Indications included Parkinson’s disease (PD) (65% of patients), essential tremor (ET) (29%), dystonia (5%), and refractory epilepsy (1%). Targets included the globus pallidus pars internus (12.62% of patients), subthalamic nucleus (56.31%), ventral intermedius nucleus of the thalamus (30%), and anterior nucleus of the thalamus (1%). Technically accurate lead placement (radial error ≤ 1 mm) was obtained for 98% of leads, with a mean (95% CI) radial error of 0.50 (0.46–0.54) mm; all leads were placed with a single pass. Predicted radial error was an excellent predictor of real radial error, underestimating real error by only a mean (95% CI) of 0.16 (0.12–0.20) mm. Accuracy remained high irrespective of surgeon experience, but procedure time decreased significantly with increasing institutional and surgeon experience (p = 0.007), with a mean procedure duration of 3.65 hours. Complications included 1 case of intracranial hemorrhage (asymptomatic) and 1 case of venous infarction (symptomatic), and 2 patients had infection at the internal pulse generator site. The mean ± SD voltage was 2.92 ± 0.83 V bilaterally at 1-year follow-up. Analysis of long-term clinical efficacy demonstrated consistent postoperative improvement in clinical symptoms, as well as decreased drug doses across all indications and follow-up time points, including mean decrease in levodopa-equivalent daily dose by 53.57% (p < 0.0001) in PD patients and mean decrease in primidone dose by 61.33% (p < 0.032) in ET patients at 1-year follow-up. CONCLUSIONS A total of 205 leads were placed in 103 patients by a single surgeon under iMRI guidance with few operative complications. Operative time trended downward with increasing institutional experience, and technical accuracy of radiographic lead placement was consistently high. Asleep DBS implantation with iMRI appears to be a safe and effective alternative to standard awake procedures.

In this article, I employ the ethnographer poetic as a strategic provocation to rethink the foundation of contemporary ethnography. The root of the word poet or poem is the ancient Greek concept of poiesis. Poiesis is defined as making. While in the Greek tradition poiesis foregrounded an analysis of the arts or aesthetics, contemporary usages highlight the making of a social or political dimension. Drawing from the social and political dimensions of poiesis, I argue that the ethnographer does more than simply represent a social context, and, instead, calls the place into existence. The ethnographer poet transforms ethnography from a representational form of inquiry into a generative poetics of place. This allows for a new social mythos to emerge in which the field of ethnography is brought into the service of envisioning and working toward a society that is hopeful, abundant, vibrant, and just.

This article focuses on war powers issues during the Clinton presidency to test the theory of nondecision-making as developed by Bachrach and Baratz (1970) and Lukes (1974). The first secti...

OBJECTIVE: To test the relationship between clinically relevant types of GBA mutations (none, risk variants, mild mutations, severe mutations) and β-glucocerebrosidase activity in patients with Parkinson disease (PD) in cross-sectional and longitudinal case-control studies. METHODS: A total of 481 participants from the Harvard Biomarkers Study (HBS) and the NIH Parkinson's Disease Biomarkers Program (PDBP) were analyzed, including 47 patients with PD carrying GBA variants (GBA-PD), 247 without a GBA variant (idiopathic PD), and 187 healthy controls. Longitudinal analysis comprised 195 participants with 548 longitudinal measurements over a median follow-up period of 2.0 years (interquartile range, 1–2 years). RESULTS: β-Glucocerebrosidase activity was low in blood of patients with GBA-PD compared to healthy controls and patients with idiopathic PD, respectively, in HBS (p < 0.001) and PDBP (p < 0.05) in multivariate analyses adjusting for age, sex, blood storage time, and batch. Enzyme activity in patients with idiopathic PD was unchanged. Innovative enzymatic quantitative trait locus (xQTL) analysis revealed a negative linear association between residual β-glucocerebrosidase activity and mutation type with p < 0.0001. For each increment in the severity of mutation type, a reduction of mean β-glucocerebrosidase activity by 0.85 μmol/L/h (95% confidence interval, −1.17, −0.54) was predicted. In a first longitudinal analysis, increasing mutation severity types were prospectively associated with steeper declines in β-glucocerebrosidase activity during a median 2 years of follow-up (p = 0.02). CONCLUSIONS: Residual activity of the β-glucocerebrosidase enzyme measured in blood inversely correlates with clinical severity types of GBA mutations in PD. β-Glucocerebrosidase activity is a quantitative endophenotype that can be monitored noninvasively and targeted therapeutically.

ObjectiveTo test the hypothesis that transcranial magnetic resonance–guided focused ultrasound (tcMRgFUS) thalamotomy is effective, durable, and safe for patients with medication-refractory essential tremor (ET), we assessed clinical outcomes at 3-year follow-up of a controlled multicenter prospective trial.MethodsOutcomes were based on the Clinical Rating Scale for Tremor, including hand combined tremor–motor (scale of 0–32), functional disability (scale of 0–32), and postural tremor (scale of 0–4) scores, and total scores from the Quality of Life in Essential Tremor Questionnaire (scale of 0–100). Scores at 36 months were compared with baseline and at 6 months after treatment to assess for efficacy and durability. Adverse events were also reported.ResultsMeasured scores remained improved from baseline to 36 months (allp< 0.0001). Range of improvement from baseline was 38%–50% in hand tremor, 43%–56% in disability, 50%–75% in postural tremor, and 27%–42% in quality of life. When compared to scores at 6 months, median scores increased for hand tremor (95% confidence interval [CI] 0–2,p= 0.0098) and disability (95% CI 1–4,p= 0.0001). During the third follow-up year, all previously noted adverse events remained mild or moderate, none worsened, 2 resolved, and no new adverse events occurred.ConclusionsResults at 3 years after unilateral tcMRgFUS thalamotomy for ET show continued benefit, and no progressive or delayed complications. Patients may experience mild degradation in some treatment metrics by 3 years, though improvement from baseline remains significant.Clinicaltrials.gov identifierNCT01827904.Classification of evidenceThis study provides Class IV evidence that for patients with severe ET, unilateral tcMRgFUS thalamotomy provides durable benefit after 3 years.

Parkinson’s disease, a degenerative neurologic condition, manifests itself differently in women than in men. Women are less likely to develop the disease and, when they do develop it, have a later onset than men. This chapter looks at a number of factors that may impact how the disease affects women differently than men including how genetic and hormonal differences may play a role. The expression of the disease, both motor and nonmotor symptoms, tends to be different in men and women also and treatment may be impacted by these differences. Finally, the data regarding pregnancy in Parkinson’s disease patients is reviewed.

Background The predominant neurosurgical approach to medication-refractory essential tremor is thalamic deep brain stimulation (DBS). The emergence of magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy has reawakened the debate surrounding the use of DBS versus thalamotomy for this indication. Herein, we aimed to provide a contemporary comparison between DBS and MRgFUS. Methods Two controlled trials that evaluated DBS and MRgFUS for the unilateral treatment of refractory essential tremor were compared. Clinical outcomes extracted included postural tremor score in the treated upper extremity, quality of life (QoL), and incidence of adverse events (AE). Results Baseline patient characteristics were comparable in the 2 studies, except that DBS patients were younger and had more severe baseline tremor. Both DBS- and MRgFUS-treated patients had significant tremor improvement that was sustained for 1-year posttreatment, and significant improvement in QoL. The MRgFUS cohort had higher rates of persistent neurologic AE, whereas the DBS group had higher rates of surgery- and hardware-related AEs, including intracranial hemorrhage. Conclusions In context of prior literature, both DBS and MRgFUS significantly improve tremor control and QoL. The 2 approaches are predominantly differentiated by their AE-profile. Additional head-to-head comparison on matched clinical populations are required to more accurately compare clinical efficacy and long-term outcomes.

Progressively less invasive neurosurgical approaches for the treatment of movement disorders have evolved, beginning with open craniotomy for placement of lesions within pyramidal structures followed by refined stereotactic ablation of extrapyramidal targets that encouraged nondestructive electrode stimulation of deep brain structures. A noninvasive approach using transcranial high-energy focused ultrasound has emerged for the treatment of intractable tremor. The ability to target discreet intracranial sites millimeters in size through the intact skull using focused acoustic energy marks an important milestone in movement disorders surgery. This article describes the evolution of magnetic resonance-guided focused ultrasound for ventrolateral thalamotomy for tremor.

There are no cures for neurodegenerative diseases and this is partially due to the difficulty of monitoring pathogenic molecules in patients during life. The Parkinson's disease gene α-synuclein (SNCA) is selectively expressed in blood cells and neurons. Here we show that SNCA transcripts in circulating blood cells are paradoxically reduced in early stage, untreated and dopamine transporter neuroimaging-supported Parkinson's disease in three independent regional, national, and international populations representing 500 cases and 363 controls and on three analogue and digital platforms with P < 0.0001 in meta-analysis. Individuals with SNCA transcripts in the lowest quartile of counts had an odds ratio for Parkinson's disease of 2.45 compared to individuals in the highest quartile. Disease-relevant transcript isoforms were low even near disease onset. Importantly, low SNCA transcript abundance predicted cognitive decline in patients with Parkinson's disease during up to 5 years of longitudinal follow-up. This study reveals a consistent association of reduced SNCA transcripts in accessible peripheral blood and early-stage Parkinson's disease in 863 participants and suggests a clinical role as potential predictor of cognitive decline. Moreover, the three independent biobank cohorts provide a generally useful platform for rapidly validating any biological marker of this common disease.

In this article the authors re-examine Sir Thomas More’s classic book Utopia as a potential source of ideas and concepts for examining, understanding and imagining contemporary education. Too often the concept utopia is used to criticize an idea, perspective or image as offering a simplistic solution to a complex problem, or, at its worst, as a model that all must be forced to accept. In our rereading of Utopia we suggest that the book and the concept can be best understood as an imaginative, critical and playful dialogue. When applied to the field of education utopia offers the potential for reimagining how we engage with and conceptualize educational theory and practice.

Object Pallidal deep brain stimulation (DBS) is a treatment option for those with early-onset dystonia. However, there are limited data on long-term outcome and treatment complications. The authors report on the short- and long-term effects of pallidal DBS in a cohort of patients with early-onset dystonia. Methods Fourteen consecutive pediatric patients with early-onset dystonia were systematically evaluated and treated. The duration of follow-up ranged from 16 to 84 months. Results There were no immediate postoperative complications. At last follow-up, 12 of the 14 patients displayed a significant decline in the Burke-Fahn-Marsden Dystonia Rating Scale motor subscale score, with an average decrease of 62% ± 8.4%. The most common hardware complication was lead fracture (14.3%). Conclusions These data provide further evidence that DBS is a safe and effective treatment for those with earlyonset dystonia.

Pharmacological therapy has had limited success in the treatment of most major neurological diseases. This has motivated the development of a number of novel surgical approaches designed to ameliorate drug-induced side effects or pharmacoresistant symptoms. Deep brain stimulation (DBS) has been quite successful in controlling both the cardinal motor manifestation of Parkinson's disease and the side effects of prolonged levodopa therapy. This has encouraged the application of DBS technology to treat a number of other neurodegenerative conditions, including secondary dystonia associated with pantothenate kinase-associated neurodegeneration (PKAN, formerly Hallervorden-Spatz syndrome), chorea associated with Huntington's disease, and most recently, cognitive decline associated with Alzheimer's type dementia. We review the rationale, indications and outcomes of neuromodulation for selected neurodegenerative conditions. In addition to DBS, we discuss select small molecule and gene-based neuromodulatory approaches. Ongoing study of basic pathophysiological mechanisms may eventually allow directed primary prevention of some of these diseases, but until then, invasive neuromoduation will likely continue to play an ever-increasing role in the delivery of the most advanced care for patients with these debilitating conditions.

Uncontrolled pilot studies have suggested the efficacy of focused ultrasound thalamotomy with magnetic resonance imaging (MRI) guidance for the treatment of essential tremor.We enrolled patients with moderate-to-severe essential tremor that had not responded to at least two trials of medical therapy and randomly assigned them in a 3:1 ratio to undergo unilateral focused ultrasound thalamotomy or a sham procedure. The Clinical Rating Scale for Tremor and the Quality of Life in Essential Tremor Questionnaire were administered at baseline and at 1, 3, 6, and 12 months. Tremor assessments were videotaped and rated by an independent group of neurologists who were unaware of the treatment assignments. The primary outcome was the between-group difference in the change from baseline to 3 months in hand tremor, rated on a 32-point scale (with higher scores indicating more severe tremor). After 3 months, patients in the sham-procedure group could cross over to active treatment (the open-label extension cohort).Seventy-six patients were included in the analysis. Hand-tremor scores improved more after focused ultrasound thalamotomy (from 18.1 points at baseline to 9.6 at 3 months) than after the sham procedure (from 16.0 to 15.8 points); the between-group difference in the mean change was 8.3 points (95% confidence interval [CI], 5.9 to 10.7; P0.001). The improvement in the thalamotomy group was maintained at 12 months (change from baseline, 7.2 points; 95% CI, 6.1 to 8.3). Secondary outcome measures assessing disability and quality of life also improved with active treatment (the blinded thalamotomy cohort)as compared with the sham procedure (P0.001 for both comparisons). Adverse events in the thalamotomy group included gait disturbance in 36% of patients and paresthesias or numbness in 38%; these adverse events persisted at 12 months in 9% and 14% of patients, respectively.MRI-guided focused ultrasound thalamotomy reduced hand tremor in patients with essential tremor. Side effects included sensory and gait disturbances. (Funded by InSightec and others; ClinicalTrials.gov number, NCT01827904.).

In this response to Yupanqui Munoz and Charbel El-Hani’s paper, “The student with a thousand faces: From the ethics in videogames to becoming a citizen”, we examine their critique of videogames in science education. Munoz and El-Hani present a critical analysis of videogames such as Grand Theft Auto, Street Fight, Command and Conquer: Generals, Halo, and Fallout 3 using Neil Postman’s (1993) conceptualization of technopoly along with Bill Green and Chris Bigum’s (1993) notion of the cyborg curriculum. Our contention is that these games are not representative of current educational videogames about science, which hold the potential to enhance civic scientific literacy across a diverse range of students while promoting cross-cultural understandings of complex scientific concepts and phenomenon. We examine games that have undergone empirical investigation in general education science classrooms, such as River City, Quest Atlantis, Whyville, Resilient Planet, and You Make Me Sick!, and discuss the ways these videogames can engage students and teachers in a constructivist dialogue that enhances science education. Our critique extends Munoz and El-Hani’s discussion through an examination of the ways videogames can enhance science education by promoting inclusive education, civic scientific literacy, and global citizenship.

In this paper, the authors imagine a Citizen of Empire. This is a conceptualization of global citizenship as it might appear in Hardt and Negri's global social order of Empire. The article draws on Hardt and Negri's Empire as the model of global society to imagine what citizenship might look like on a global scale. Hardt and Negri's conceptualization of Empire offers a palette of new and emerging social relationships from which a vibrant conceptualization of citizen and citizenship can be imagined and new democratic politics practiced. First, the authors examine the concept of Empire to unearth foundational concepts upon which a notion of Citizen of Empire can be built. Second, the authors imagine a citizen who ‘calls Empire into being' rather than participating in the ready-made political, cultural, and economic institutions of the nation-state. Without institutional support, citizenship in Empire must be highly generative and creative, and it will operate on a virtual and poetic terrain by enacting mech...

This article reports the findings of a study examining independent variables that contributed to the science, technology, engineering, and mathematics (STEM) achievement of students with reading difficulties who participated in a technology-enhanced astronomy curriculum. The curriculum incorporated key elements of the Universal Design for Learning (UDL) theoretical framework. Participants (N = 1153) included middle school students from 64 inclusive science classrooms. A two-level hierarchical linear model was developed to determine the contribution of student- and teacher/classroom-level factors to the prediction of posttest and problem-solving scores. Results reveal differences across schools in the effect of being in a lower reading ability group on performance on the posttest and problem-solving measures, with some students performing at a level commensurate with their proficient reading peers. Factors associated with differential performance are identified. Implications of these findings are discussed. Areas for future research are identified.

The central hypothesis of all policy typologies is that distinctively different patterns of politics can be identified for different types of public policy issues. Lowi identified three different policy types, which he termed distributive, regulative, and redistributive, each of which triggers a distinctively different pattern of political behavior. Unfortunately, Lowi's categories were inductively derived and ambiguously defined, leading to disagreements over how to categorize particular policies. Hayes built on Lowi's seminal effort, deriving Lowi's three policy categories from two underlying dimensions and identifying additional categories Lowi's original formulation had missed. Using the minimum wage issue as an example, this article will identify a critical deficiency in both these typologies. While Hayes' typology defines the boundaries between policy categories more precisely than Lowi's, neither typology is equipped to deal with variations in political patterns occurring within a particular cell. As this article will show, the minimum wage issue, although consistently redistributive in Hayes' terms, has manifested three very different patterns of politics at different points in time. Accordingly, a typology of redistributive policies will be advanced to account for these variations in the redistributive politics of the minimum wage.

In the article the authors argue for the imagination as a central method in ethnography employed to create a more abundant, just, and connected planet. Imagination is the creative energy that links conscious with the generation of the world of material experience. Through imagination the ethnographer becomes immersed in a space of play in which the world can be imagined as something not yet or in emergence, rather than as it is. Our hope is that by employing imagination in this way, ethnography can be focused to generating new possibilities for life on the planet.

Twenty-two faculty and graduate students were interviewed in one college of education in order to understand what the college and its constituents view as the skills, habits of mind, and dispositions needed to obtain a Ph.D. in Education. Analysis of the data was conducted using professional socialization as a theoretical framework, allowing for an understanding of the different perspectives of this topic as viewed through a developmental lens. Implications for theory and practice are included.

In this article the authors present their analysis of preservice teachers’ video production. Twenty‐eight students in the first authors’ Social Foundations of the Elementary Curriculum course produced a 5‐ to 10‐minute video as the major assignment for the class, interviews were conducted with six of the seven video production groups and the videos were analyzed with regard to the interviews and theories of visual culture. The authors suggest that in the video products and in the production process the students exhibited a cultural logic of media imagery. The particular logics of audience and entertainment served as a concealed organizing principle for how the students thought about their videos and the processes involved in making them. Embedded in this logic was an overarching concern that their work occupy a public space, thus troubling the boundaries of consumption and production that frame how we consider the role media culture plays in the processes of human meaning‐making.

Objective This study evaluated validity and reliability of automated median and ulnar sensory nerve conduction study (NCS) measurements by the NC-stat ® . Methods Median and ulnar distal sensory latencies (DSL) and amplitudes (SNAP) were measured in sixty subjects with the NC-stat and by a neurologist (reference) using traditional instrumentation. The median–ulnar DSL differences (MUD) was calculated. Validity was quantified by the Pearson correlation. Reliability was evaluated by the intraclass correlation coefficient (ICC), Bland–Altman analysis, and inter-rater agreement of MUD abnormalities. Results As a result of differences in electrode placement, NC-stat and reference mean values had systematic differences. The correlation ranged from 0.70 (ulnar DSL) to 0.91 (median DSL). The ICC ranged from 0.69 (ulnar DSL) to 0.91 (median DSL). In Bland–Altman analysis of DSLs, NC-stat measurements had a bias of 0.56ms (median) and 0.31ms (ulnar) and precision of 0.31 and 0.30ms. Inter-rater agreement for MUD abnormalities was 93.8% (raw) and 0.80 (Kappa). Conclusions NC-stat validity and reliability metrics were similar to traditional NCS. Use of the NC-stat would require applicable reference ranges. Significance NC-stat median and ulnar NCS are valid and reliable. This device may be useful for increasing availability of NCS when clinically appropriate.

There is no doubt that today's schools are faced with the challenge of educating an increasingly diverse school population. More teacher education programs address these challenges by adding courses in multicultural education and/or infusing content on teaching culturally and linguistically diverse students into the existing curriculum. This investigation reports on the changes in concepts and beliefs of 45 preservice teachers enrolled in a 17-week unified early childhood/special education multicultural education course. The course consisted of topics related to teaching students from culturally and linguistically diverse backgrounds. Instructors used a variety of pedagogical strategies in the course including small group activities, case study illustrations, videotapes, thematic unit instruction, and traditional large group lectures. Students were asked to draw concept maps on “multicultural education” and write explanatory paragraphs on the first and last day of the course. Conceptual and belief changes were found in both the concept maps and supporting paragraphs.

(2002). Elementary Preservice Teachers' Struggles to Define Inquiry-Based Science Teaching. Journal of Science Teacher Education: Vol. 13, No. 2, pp. 147-165.

The research described in this article is a case study of a fifth grade teacher's (Melissa) efforts to construct a teaching and learning environment within her science teaching. Qualitative research methods were used to examine and analyze Melissa's science teaching practice. Drawing from socio-cultural theories, I argue that her teaching and learning environment was constructed as a form of mediated action through which she articulated and transformed the context, meaning, and action of her science teaching. In particular, she forged links between a number of factors, such as historically recognizable forms of pedagogy, perceptions of her students' socio-economic positions, knowledge of appropriate science teaching, and her experiences in a preservice teacher education program. Through her pedagogical work, the teaching and learning environment was articulated into a complex network of meanings, physical spaces, and concrete actions in which each element transformed the other. I suggest that mediated action is a form of transformation that constitutes context, meaning, and action into a dynamic and constantly-shifting teaching and learning environment.

In this article, the author develops a theory of white racial identity as a political alliance. He argues that a racial identity is inherently a social relationship that is immersed in institutional and everyday power arrangements and that formulating a racial identity is an inherently political process that involves the articulation of politically committed relationships, which are alliances. Using examples from academic literature and personal experience, the author illustrates how racial identity is articulated within the constant tension between historical and institutional structures and human agency. The implications are twofold. First, whites must acknowledge and take responsibility for the historically derived systems of privilege that place them into alliances with each other. Second, whites must also understand that reformulating a racial identity entails the development of social relationships that, because they are racial in nature, are inherently political. This means that constructing a white racial identity is a form of political action that requires a conscious effort to develop an anti-racist identity that embraces the possibility and need for social justice.

The research described in this article was a comparative study of science curriculum differentiation at two elementary schools that served students from different socioeconomic and ethnic backgrounds. Two schools in the same school district, Lake and Jefferson, were the sites for the research. Lake Elementary served a professional class and white neighborhood, but Jefferson Elementary served students from working-class/working poor and ethnically diverse backgrounds. The teachers and students in a fifth and sixth grade classroom at each school participated in the research. Research methods drew from ethnographic and linguistic traditions and focused on the microlevel everyday classroom interactions in which the curriculum is constructed. The results of the study show that the science curriculum was quite different between the two schools. The science curriculum at Lake emphasized organization and control for the purpose of preparing students for traditional notions of academic success and progress. At Jefferson, the science curriculum was constructed within an informal and conversational format in an effort to engage students in science. We suggest that it is difficult to determine if and how this curriculum differentiation might establish or enhance inequality in science education. Instead, we offer competing interpretations of the results that draw from current notions of best practice in the science education community. © 2001 John Wiley & Sons, Inc. Sci Ed85:239–262, 2001.