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Choline is an essential nutrient that the human body needs in vast quantities for cell membrane synthesis, epigenetic modification and neurotransmission. The brain has a particularly high demand for choline, but how it enters the brain remains unknown1-3. The major facilitator superfamily transporter FLVCR1 (also known as MFSD7B or SLC49A1) was recently determined to be a choline transporter but is not highly expressed at the blood-brain barrier, whereas the related protein FLVCR2 (also known as MFSD7C or SLC49A2) is expressed in endothelial cells at the blood-brain barrier4-7. Previous studies have shown that mutations in human Flvcr2 cause cerebral vascular abnormalities, hydrocephalus and embryonic lethality, but the physiological role of FLVCR2 is unknown4,5. Here we demonstrate both in vivo and in vitro that FLVCR2 is a BBB choline transporter and is responsible for the majority of choline uptake into the brain. We also determine the structures of choline-bound FLVCR2 in both inward-facing and outward-facing states using cryo-electron microscopy. These results reveal how the brain obtains choline and provide molecular-level insights into how FLVCR2 binds choline in an aromatic cage and mediates its uptake. Our work could provide a novel framework for the targeted delivery of therapeutic agents into the brain.
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Encéfalo , Colina , Proteínas de Membrana Transportadoras , Animais , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Transporte Biológico , Barreira Hematoencefálica/metabolismo , Encéfalo/metabolismo , Colina/metabolismo , Microscopia Crioeletrônica , Técnicas In Vitro , Proteínas de Membrana Transportadoras/química , Proteínas de Membrana Transportadoras/metabolismo , Proteínas de Membrana Transportadoras/ultraestrutura , Modelos MolecularesRESUMO
OBJECTIVE: This study presents data for using accelerated transcranial magnetic stimulation (TMS) as an intervention for suicidal crisis (SC). METHODS: This prospective, single-site, randomized, double-blind trial enrolled active-duty military participants with SC to receive either active TMS (n = 59) or sham TMS (n = 61) 3 times per day for 3 consecutive days. Our primary outcome, the Beck Scale for Suicidal Ideation-current (SSI-C), was measured before each session of TMS. Secondary outcomes measured both the SSI-C and the Beck Scale for Suicidal Ideation-total daily for the 3 intervention days and at 1, 3, and 6 months of follow-up. RESULTS: In the modified intention to treat (mITT) analysis of SSI-C changes over treatment sessions, the TMS active group had accelerated decline in suicidal ideation as compared with sham: ß for interaction was 0.12 points greater SSI-C decline per session (standard error [SE], 0.06) in TMS versus sham (P = 0.04). In both the mITT and per-protocol active TMS groups, the mean final SSI-C scores were below 3. These scores remained below 3 for the entire 6-month follow-up period. CONCLUSIONS: In this military trial of suicidal patients, we found that both active and sham accelerated TMS rapidly reduces SC. Moreover, in the mITT analysis, there was a statistically significant antisuicidal benefit of active TMS versus sham TMS in the primary outcome. Both the mITT and per-protocol groups moved from higher to approximately 7 times lower suicide risk strata and remained there for the duration of the study. Further studies are warranted to understand accelerated TMS' full potential as a treatment for SC.
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Eletroconvulsoterapia , Militares , Humanos , Estudos Prospectivos , Ideação Suicida , Estimulação Magnética Transcraniana/métodos , Resultado do TratamentoRESUMO
OBJECTIVES: The prevalence of depression and insomnia in the military are substantial. Several transcranial magnetic stimulation (TMS) studies have used self-report sleep data as secondary research outcomes; however, there are limited studies using the gold standard of polysomnography (PSG) to ascertain actual sleep changes. Here, we provide data from a pilot and feasibility study using PSG to measure sleep changes after repetitive TMS. METHODS: Thirty-eight active duty service members (ADSM) were consented, of which 20 completed the study. The ADSM who met study criteria where sent for an initial PSG and completed baseline self-report measures. They then completed a standard course of TMS, and self-report measures were completed every fifth session. After TMS completion, ADSM underwent final PSG. RESULTS: Comparison of baseline and postintervention PSG sleep parameters highlight that total rapid eye movement sleep improved after a course of TMS, regardless of improvements in depression. Total sleep time also improved, but only in the TMS responders subgroup. The Public Health Questionnaire-9 showed statistically significant improvement as did the Insomnia Severity Index and some components of the RAND Medical Outcomes Short Form 36. CONCLUSION: Our small study confirms the feasibility of obtaining pre and post PSG for research purposes. We found similar results to previous studies with regard to depression improvement and self-reported sleep. Interestingly, almost all (including electroconvulsive therapy) somatic depression treatments have been shown to decrease REM, whereas our study found an increase in REM. Overall, this study helps further our understanding of TMS effects on sleep and presents new questions for potential larger follow-on studies.
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Eletroconvulsoterapia , Sono REM , Depressão/terapia , Humanos , Polissonografia , Sono , Estimulação Magnética TranscranianaRESUMO
The contrast sensitivity function (CSF) is an informative measure of visual health, but the practical difficulty of measuring it has impeded detailed analyses of its relationship to different visual disorders. Furthermore, most existing tasks cannot be used in populations with cognitive impairment. We analyzed detailed CSFs measured with a nonverbal procedure called "Gradiate," which efficiently infers visibility from eye movements and manipulates stimulus appearance in real time. Sixty observers of varying age (38 with refractive error) were presented with moving stimuli. Stimulus spatial frequency and contrast advanced along 15 radial sweeps through CSF space in response to stimulus-congruent eye movements. A point on the CSF was recorded when tracking ceased. Gradiate CSFs were reliable and in high agreement with independent low-contrast acuity thresholds. Overall CSF variation was largely captured by two orthogonal factors ("radius" and "slope") or two orthogonal shape factors when size was normalized ("aspect ratio" and "curvature"). CSF radius was highly predictive of LogMAR acuity, as were aspect ratio and curvature together, but only radius was predictive of observer age. Our findings suggest that Gradiate holds promise for assessing spatial vision in both verbal and nonverbal populations and indicate that variation between detailed CSFs can reveal useful information about visual health.
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Sensibilidades de Contraste/fisiologia , Movimentos Oculares/fisiologia , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Percepção de Movimento/fisiologia , Processamento Espacial , Acuidade Visual/fisiologia , Adulto JovemRESUMO
OBJECTIVES: Current research on the efficacy of repetitive transcranial magnetic stimulation (rTMS) over left dorsolateral prefrontal cortex as a noninvasive therapy for treatment-resistant depression is largely settled science. However, little is known about its efficacy with active-duty service members (ADSMs) with major depressive disorder. In a retrospective chart review, we examined depressive symptom ratings in ADSMs seeking treatment at the US Army Outpatient Behavioral Health Service Clinic at Eisenhower Army Medical Center, Fort Gordon, Ga. METHODS: We reviewed 121 consecutive outpatient charts, which yielded 61 ADSMs who completed a minimum of 20 rTMS sessions for refractory depression, and for whom both pretreatment and posttreatment depressive symptom ratings were available. Pre- and post-Patient Health Questionnaire 9 (PHQ-9) scores were subjected to a paired t test, and Reliable Change Indices were calculated to determine both reliable and clinical significance. RESULTS: Average (SD) pretreatment and posttreatment PHQ-9 scores were 15.8 (6.2) and 12.6 (7.6), respectively. Statistically significant reduction in post-PHQ-9 was demonstrated (P < 0.001), with 69% of patients lowering their ratings and 31% demonstrating reliable change (improvement >5.64). Additionally, 20% demonstrated a reliable change that placed them in the nondysfunctional range (post-PHQ-9 <9.6), demonstrating clinical significance. CONCLUSIONS: These data confirm a course of standard rTMS to ADSMs with major depression is promising in reducing depressive symptoms. Given that success and completion rates from this clinic are similar to those reported in civilian populations (80%), rTMS may be an adequate additional treatment or augmentation strategy for refractory depression in ADSMs.
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Transtorno Depressivo Resistente a Tratamento/terapia , Militares , Estimulação Magnética Transcraniana , Adulto , Feminino , Humanos , Masculino , Estudos Retrospectivos , Inquéritos e Questionários , Estados UnidosRESUMO
The contrast sensitivity function (CSF) is an informative measure of visual function, but current tools for assessing it are limited by the attentional, motor, and communicative abilities of the participant. Impairments in these abilities can prevent participants from engaging with tasks or following an experimenter's instructions. Here, we describe an efficient new tool for measuring contrast sensitivity, Curveball, and empirically validate it with a sample of healthy adults. The Curveball algorithm continuously infers stimulus visibility through smooth eye tracking instead of perceptual report, and rapidly lowers stimulus contrast in real time until a threshold is found. The procedure requires minimal instruction to administer and takes only five minutes to estimate a full CSF, which is comparable to the best existing methods available for healthy adults. Task repeatability was high: the coefficients of repeatability were 0.275 (in log10 units of RMS contrast) within the same session and 0.227 across different days. We also present evidence that the task is robust across illumination changes, well correlated with results from conventional psychophysical methods, and highly sensitive to improvements in visual acuity from refractive correction. Our findings indicate that Curveball is a promising means of accurately assessing contrast sensitivity in previously neglected populations.
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Sensibilidades de Contraste/fisiologia , Acompanhamento Ocular Uniforme/fisiologia , Testes Visuais/instrumentação , Adulto , Algoritmos , Feminino , Humanos , Masculino , Psicofísica , Acuidade Visual/fisiologia , Adulto JovemRESUMO
Wartime experiences have long been known to cause ethical conflict, guilt, self-condemnation, difficulty forgiving, loss of trust, lack of meaning and purpose, and spiritual struggles. "Moral injury" (MI) (also sometimes called "inner conflict") is the term used to capture this emotional, cognitive, and behavioral state. In this article, we provide rationale for developing and testing Spiritually Oriented Cognitive Processing Therapy, a version of standard cognitive processing therapy for the treatment of MI in active duty and veteran service members (SMs) with posttraumatic stress disorder symptoms who are spiritual or religious (S/R). Many SMs have S/R beliefs that could increase vulnerability to MI. Because the injury is to deeply held moral standards and ethical values and often adversely affects spiritual beliefs and worldview, we believe that those who are S/R will respond more favorably to a therapy that directly targets this injury from a spiritually oriented perspective. An evidence-based treatment for MI in posttraumatic stress disorder that not only respects but also utilizes SMs' spiritual beliefs/behaviors may open the door to treatment for many S/R military personnel.
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Terapia Cognitivo-Comportamental/métodos , Emoções , Militares/psicologia , Princípios Morais , Espiritualidade , Transtornos de Estresse Pós-Traumáticos/terapia , Veteranos/psicologia , Conflito Psicológico , Humanos , Transtornos de Estresse Pós-Traumáticos/psicologiaRESUMO
Background We observed cases of extensive osteolysis of the femoral head following acetabular fractures even though the original fracture did not involve the femoral head or neck. This observation has been called massive osteolysis of the femoral head (MOFH). Purpose To evaluate the clinical and imaging features of MOFH to gain a better understanding of its patho-etiology. Material and Methods We retrospectively collected cases of acetabular fractures seen over a period of 10 years and evaluated the clinical features and imaging characteristics. The findings were compared with the features of other complications such as osteonecrosis, rapidly progressive osteoarthritis, or post-traumatic osteolysis. Results Fifteen patients (M:F ratio 9:6; mean age, 61.6 years) out of 244 had MOFH (prevalence: 6.1%). Motor vehicle collision and falls were the most common mechanisms of injury. The time interval for developing MOFH was in the range of 1-18 months after the initial injury. Patterns of femoral head osteolysis varied from eccentric (12 cases) to transcervical (3 cases). Four cases of eccentric osteolysis developed high-degree of osteolysis. MOFH was observed near the surgical hardware in 6/15 cases. One biopsy specimen did not reveal typical features of osteoarthritis or avascular necrosis. Conclusion MOFH appears to be a distinct entity from avascular necrosis or rapidly progressive osteoarthritis. It is suggested that MOFH is a variant of post-traumatic osteolysis that is evident in a subset of patients.
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Acetábulo/lesões , Cabeça do Fêmur , Fraturas Ósseas/complicações , Osteólise Essencial/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
Around 88 large vertebrate taxa disappeared from Sahul sometime during the Pleistocene, with the majority of losses (54 taxa) clearly taking place within the last 400,000 years. The largest was the 2.8-ton browsing Diprotodon optatum, whereas the â¼100- to 130-kg marsupial lion, Thylacoleo carnifex, the world's most specialized mammalian carnivore, and Varanus priscus, the largest lizard known, were formidable predators. Explanations for these extinctions have centered on climatic change or human activities. Here, we review the evidence and arguments for both. Human involvement in the disappearance of some species remains possible but unproven. Mounting evidence points to the loss of most species before the peopling of Sahul (circa 50-45 ka) and a significant role for climate change in the disappearance of the continent's megafauna.
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Mudança Climática , Extinção Biológica , Vertebrados , Animais , Arqueologia , Austrália , História Antiga , Atividades Humanas/história , Humanos , Nova Guiné , Paleontologia/métodos , Especificidade da EspécieRESUMO
Brain injury can cause many distinct types of visual impairment in children, but these deficits are difficult to quantify due to co-morbid deficits in communication and cognition. Clinicians must instead rely on low-resolution, subjective judgements of simple reactions to handheld stimuli, which limits treatment potential. We have developed an interactive assessment program called the Visual Ladder, which uses gaze-based responses to intuitive, game-like tasks to address the lack of broad-spectrum quantified data on the visual abilities of children with brain injury. Here, we present detailed metrics on eye movements, field asymmetries, contrast sensitivity, and other critical visual abilities measured longitudinally using the Ladder in hospitalized children with varying types and degrees of brain injury, many of whom were previously considered untestable. Our findings show which abilities are most likely to exhibit recovery and reveal how distinct patterns of task outcomes defined unique diagnostic clusters of visual impairment.
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Introduction: AI technologies have the potential to transform patient care. AI has been used to aid in differential diagnosis and treatment planning for psychiatric disorders, administer therapeutic protocols, assist with interpretation of cognitive testing, and patient treatment planning. Despite advancements, AI has notable limitations and remains understudied and further research on its strengths and limitations in patient care is required. This study explored the responses of AI (Chat-GPT 3.5) and trained clinicians to commonly asked patient questions. Methods: Three clinicians and AI provided responses to five dementia/geriatric healthcare-related questions. Responses were analyzed by a fourth, blinded clinician for clarity, accuracy, relevance, depth, and ease of understanding and to determine which response was AI generated. Results: AI responses were rated highest in ease of understanding and depth across all responses and tied for first for clarity, accuracy, and relevance. The rating for AI generated responses was 4.6/5 (SD = 0.26); the clinician s' responses were 4.3 (SD = 0.67), 4.2 (SD = 0.52), and 3.9 (SD = 0.59), respectively. The AI generated answers were identified in 4/5 instances. Conclusions: AI responses were rated more highly and consistently on each question individually and overall than clinician answers demonstrating that AI could produce good responses to potential patient questions. However, AI responses were easily distinguishable from those of clinicians. Although AI has the potential to positively impact healthcare, concerns are raised regarding difficulties discerning AI from human generated material, the increased potential for proliferation of misinformation, data security concerns, and more.
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The human visual system is tasked with the problem of extracting information about the world from images that contain a conflated mixture of environmental sources and optical artifacts generated by the focal properties of our eyes. In most contexts, our brains manage to distinguish these sources, but this is not always the case. Recent work showed that shading gradients generated by smooth three-dimensional (3D) surfaces can elicit strong illusory percepts of optical defocus1,2 - the perception of illusory blur is only eliminated when the surface appears attached to self-occluding contours3, surface discontinuities1, or sharp specular reflections1,2, which all generate sharp ('high spatial frequency') image structure. This suggests that it should also be possible to eliminate the illusory blur elicited by shaded surfaces by altering the surface geometry to include small-scale surface relief, which would also generate high-frequency image structure. We report the surprising result here that this manipulation fails to eliminate the perception of blur; the fine texture fails to perceptually 'bind' to the low-frequency image structure when there is a sufficient gap between the spatial scales of the fine and coarse surface structure. These findings suggest that discontinuous 'gaps' in the spatial scale of textures are a segmentation cue the visual system uses to extract multiple causes of image structure.
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Percepção de Forma , Ilusões , Humanos , Olho , EncéfaloRESUMO
Background: A 76-year-old male Veteran with a historical diagnosis of mild cognitive impairment was assessed at baseline and follow-up as part of two separate, ongoing studies. He was diagnosed with COVID-19 during the interim. Objective: To report potential effects on cognitive and functional abilities measured before and after contracting COVID-19. Methods: The patient was administered a series of cognitive tests and self-report procedures assessing cognitive, functional, and neuropsychiatric status. Results: Overall, no discernable pattern of cognitive changes between pre-COVID and post-COVID assessments were noted. Only mild increases in agitation, depression, and irritability were noted on a self-report measure. However, this particular subject has relatively ideal psychosocial circumstances in comparison to the typical older adult Veteran male. It is hypothesized that improved psychosocial conditions will result in less negative cognitive and functional outcomes for older adults diagnosed with COVID-19. Conclusion: High levels of resilience, social support, and exercise, coupled with lower levels of perceived stress and loneliness may serve as protective factors against cognitive and functional decline in older adults who contract COVID-19.
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INTRODUCTION: Military sexual trauma (MST) has been a concern within our U.S. military for many years. Many interventions have been found to benefit this population, although meaning-based interventions are still lacking in this area. The purpose of this phenomenological study is to understand the meaning-making process and themes that arise for female military veterans as they narrate their experience(s) of MST. MATERIALS AND METHODS: The qualitative study consisted of six female participants, from different areas across the nation, who all reported experiencing MST during their time in service. Their experiences of MST included both sexual harassment and sexual assault. Participants completed a semi-structured interview that was analyzed using an axial coding method to discover the major themes of each participant's interview. The participants discussed the positive and negative aspects of their journey following their MST experience(s). This study's procedures were approved by Adler University's Institutional Review Board. RESULTS: Many found the interview to be a healing experience on their path of post-traumatic growth (PTG). There were eight major themes that arose from the data analysis under the three main domains of (1) creating a work or doing a deed, (2) experiencing something or encountering someone in a way to produce PTG, and (3) altering one's attitude toward unavoidable suffering. The eight themes were as follows: advocacy, adaptive coping, sense of family unit, psychological clarity, meaningful mantra, survivor mentality code, view of self in the world, and resiliency. CONCLUSIONS: All participants endorsed engagement in some type of activity that fell into one of the three major domains identified above. This finding helped highlight the PTG that participants were able to experience through their meaning-making journey. There were several recommendations and study implications that were derived from this research study. With the themes introduced from this study, future treatment planning for individual survivors of MST can be better informed by the utilization of meaning-making techniques. Family and group meaning-based interventions would also be an area of continued exploration for this population. Future implications for practice are also included within this article. Significant limitations of the study include amount of participants, lack of diversity in sample population, qualitative study results, and lack of a more-personal interviewing process.
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The alpine area of the Australian mainland is highly sensitive to climate and environmental change, and potentially vulnerable to ecosystem tipping points. Over the next two decades the Australian alpine region is predicted to experience temperature increases of at least 1 °C, coupled with a substantial decrease in snow cover. Extending the short instrumental record in these regions is imperative to put future change into context, and potentially provide analogues of warming. We reconstructed past temperatures, using a lipid biomarker palaeothermometer technique and mercury flux changes for the past 3500 years from the sediments of Club Lake, a high-altitude alpine tarn in the Snowy Mountains, southeastern Australia. Using a multi-proxy framework, including pollen and charcoal analyses, high-resolution geochemistry, and ancient microbial community composition, supported by high-resolution 210Pb and AMS 14C dating, we investigated local and regional ecological and environmental changes occurring in response to changes in temperature. We find the region experienced a general warming trend over the last 3500 years, with a pronounced climate anomaly occurring between 1000 and 1600 cal yrs. BP. Shifts in vegetation took place during this warm period, characterised by a decline in alpine species and an increase in open woodland taxa which co-occurred with an increase in regional fire activity. Given the narrow altitudinal band of Australian alpine vegetation, any future warming has the potential to result in the extinction of alpine species, including several endemic to the area, as treelines are driven to higher elevations. These findings suggest ongoing conservation efforts will be needed to protect the vulnerable alpine environments from the combined threats of climate changes, fire and invasive species.
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Ecossistema , Incêndios , Austrália , Mudança Climática , FlorestasRESUMO
Visual deficits in children that result from brain injury, including cerebral/cortical visual impairment (CVI), are difficult to assess through conventional methods due to their frequent co-occurrence with cognitive and communicative disabilities. Such impairments hence often go undiagnosed or are only determined through subjective evaluations of gaze-based reactions to different forms, colors, and movements, which limits any potential for remediation. Here, we describe a novel approach to grading visual health based on eye movements and evidence from gaze-based tracking behaviors. Our approach-the "Visual Ladder"-reduces reliance on the user's ability to attend and communicate. The Visual Ladder produces metrics that quantify spontaneous saccades and pursuits, assess visual field responsiveness, and grade spatial visual function from tracking responses to moving stimuli. We used the Ladder to assess fourteen hospitalized children aged 3 to 18 years with a diverse range of visual impairments and causes of brain injury. Four children were excluded from analysis due to incompatibility with the eye tracker (e.g., due to severe strabismus). The remaining ten children-including five non-verbal children-were tested multiple times over periods ranging from 2 weeks to 9 months, and all produced interpretable outcomes on at least three of the five visual tasks. The results suggest that our assessment tasks are viable in non-communicative children, provided their eyes can be tracked, and hence are promising tools for use in a larger clinical study. We highlight and discuss informative outcomes exhibited by each child, including directional biases in eye movements, pathological nystagmus, visual field asymmetries, and contrast sensitivity deficits. Our findings indicate that these methodologies will enable the rapid, objective classification and grading of visual impairments in children with CVI, including non-verbal children who are currently precluded from most vision assessments. This would provide a much-needed differential diagnostic and prognostic tool for CVI and other impairments of the visual system, both ocular and cerebral.
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INTRODUCTION: Traumatic Brain Injury (TBI) is a prevalent health issue in the US and even more prevalent amongst members of the armed forces. The purpose of this project was to evaluate the association between history of TBI and rates of dental treatment performed, endodontic therapy, and high caries risk. METHODS: This was a retrospective medical and dental records study. The first 100 of a chosen dental hygienist's patients in 2016 who were seen for dental prophylaxis appointments were chosen as subjects. Armed Forces Health Longitudinal Technology Application (AHLTA) and Corporate Dental System (CDS) records were used to gather information on these subjects including rank, age, gender, duty status, tobacco use, history of TBI, total number of dental procedures, total Dental Weighted Value (DWV), number of endodontic procedures, endodontic DWV, high caries risk categorization, total days dental fitness class 1, and total days dental fitness class 3. From these subjects, a "TBI group" and a "Non-TBI group" were formed. T-Test analyses were performed to compare these groups to each other in categories of total number of dental procedures, total DWV, total days dental fitness class 1, and total days class 3. Relative risks ratio analysis was used to compare these groups in terms of high caries risk categorization. RESULTS: Eight out of 100 subjects had a history of TBI. All TBI events were mild. Six subjects had 1 event, 1 had 2 events, and 1 had 4 events. The TBI group had a statistically higher mean number of dental procedures (P=0.00000025) and mean total DWV (P=0.0000062) compared to the non-TBI group. No subjects from the TBI group had an endodontic procedure. The TBI group had lower mean days in dental fitness class 1 and more mean days in dental fitness class 3, but the results were not statistically significant. The TBI group had lower high caries risk categorization rates than the non-TBI group, but the results were not statistically significant. CONCLUSIONS: Patients with a history of TBI had a significantly higher number of dental procedures performed and DWV generated compared to patients without a history of TBI.
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Lesões Encefálicas Traumáticas , Militares , Lesões Encefálicas Traumáticas/epidemiologia , Assistência Odontológica , Suscetibilidade à Cárie Dentária , Humanos , Estudos RetrospectivosRESUMO
In neuroscientific experiments and applications, working with auditory stimuli demands software tools for generation and acquisition of raw audio, for composition and tailoring of that material into finished stimuli, for precisely timed presentation of the stimuli, and for experimental session recording. Numerous programming tools exist to approach these tasks, but their differing specializations and conventions demand extra time and effort for integration. In particular, verifying stimulus timing requires extensive engineering effort when developing new applications. This paper has two purposes. The first is to present audiomath (https://pypi.org/project/audiomath), a sound software library for Python that prioritizes the needs of neuroscientists. It minimizes programming effort by providing a simple object-oriented interface that unifies functionality for audio generation, manipulation, visualization, decoding, encoding, recording, and playback. It also incorporates specialized tools for measuring and optimizing stimulus timing. The second purpose is to relay what we have learned, during development and application of the software, about the twin challenges of delivering stimuli precisely at a certain time, and of precisely measuring the time at which stimuli were delivered. We provide a primer on these problems and the possible approaches to them. We then report audio latency measurements across a range of hardware, operating systems and settings, to illustrate the ways in which hardware and software factors interact to affect stimulus presentation performance, and the resulting pitfalls for the programmer and experimenter. In particular, we highlight the potential conflict between demands for low latency, low variability in latency ("jitter"), cooperativeness, and robustness. We report the ways in which audiomath can help to map this territory and provide a simplified path toward each application's particular priority. By unifying audio-related functionality and providing specialized diagnostic tools, audiomath both simplifies and potentiates the development of neuroscientific applications in Python.
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Objectives: Plantar heel pain (PHP) is the most common cause of heel pain and can be debilitating; 20% of patients are refractory to standard of care. The Fascial Distortion Model (FDM), a novel manual diagnostic and treatment strategy, is purported to be effective for chronic pain; however, no rigorous studies document its effectiveness. We assessed the FDM for care of PHP. Design: Single arm prospective effectiveness study. Settings/Location: Outpatient primary care clinic; Fort Gordon, GA. Subjects: Outpatient adults. Interventions: Participants received an FDM-informed diagnostic and treatment strategy to identify fascial "distortions" at the foot based on patient-reported pain patterns and palpatory examination and then to provide distortion-specific manual therapy at baseline and 1 week. Outcome Measures: Primary outcome measure (0, 1, and 16 weeks): the Foot Pain subscale on the validated Foot Health Status Questionnaire (FHSQ; 0-100 points on each of eight separate subscales); secondary outcome measures (0, 1, and 16 weeks): the seven remaining subscales on the FHSQ, visual analog pain scale (VAS, 0-100 points), and plantar fascia thickness of the most effected foot assessed by ultrasound (0 and 16 weeks). Analysis was performed per protocol using repeated-measures analysis of variance. Results: One hundred and ninety-seven participants were screened; 33 were enrolled. Twenty-eight participants received two FDM procedures. Compared with baseline, improvement on the FHSQ Foot Pain (33.8-23.6 points) and Foot Function (23.9-19.8 points) subscales and VAS (44.7-27.7 points) at 16 weeks was statistically significant (all p's < 0.001) and clinically important representing large effect sizes. Relative to baseline, 16-week ultrasound demonstrated reduced average plantar fascia thickness (0.6-0.9 mm [p = 0.001]). Demographic characteristics were unrelated to response. Satisfaction was high. There were no serious adverse events; side effects included consistent mild-to-moderate self-limited pain. Conclusions: Participants with PHP who received FDM-informed care reported significant and sustained improvement on validated foot pain and foot function measures; additional findings included decreased plantar fascial thickness. These results require corroboration in a larger randomized controlled study. Clinical Trial Registration No: DDEAMC17005.