Exploring Transfers between Earth-Moon Halo Orbits via Multi-Objective Reinforcement Learning.

Multi-Reward Proximal Policy Optimization, a multi-objective deep reinforcement learning algorithm, is used to examine the design space of low-thrust trajectories for a SmallSat transferring between two libration point orbits in the Earth-Moon system. Using Multi-Reward Proximal Policy Optimization, multiple policies are simultaneously and efficiently trained on three distinct trajectory design scenarios. Each policy is trained to create a unique control scheme based on the trajectory design scenario and assigned reward function. Each reward function is defined using a set of objectives that are scaled via a unique combination of weights to balance guiding the spacecraft to the target mission orbit, incentivizing faster flight times, and penalizing propellant mass usage. Then, the policies are evaluated on the same set of perturbed initial conditions in each scenario to generate the propellant mass usage, flight time, and state discontinuities from a reference trajectory for each control scheme. The resulting low-thrust trajectories are used to examine a subset of the multi-objective trade space for the SmallSat trajectory design scenario. By autonomously constructing the solution space, insights into the required propellant mass, flight time, and transfer geometry are rapidly achieved.

A multivariate neuroimaging biomarker of individual outcome to transcranial magnetic stimulation in depression.

The neurobiology of major depressive disorder (MDD) remains incompletely understood, and many individuals fail to respond to standard treatments. Repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex (DLPFC) has emerged as a promising antidepressant therapy. However, the heterogeneity of response underscores a pressing need for biomarkers of treatment outcome. We acquired resting state functional magnetic resonance imaging (rsfMRI) data in 47 MDD individuals prior to 5-8 weeks of rTMS treatment targeted using the F3 beam approach and in 29 healthy comparison subjects. The caudate, prefrontal cortex, and thalamus showed significantly lower blood oxygenation level-dependent (BOLD) signal power in MDD individuals at baseline. Critically, individuals who responded best to treatment were associated with lower pre-treatment BOLD power in these regions. Additionally, functional connectivity (FC) in the default mode and affective networks was associated with treatment response. We leveraged these findings to train support vector machines (SVMs) to predict individual treatment responses, based on learned patterns of baseline FC, BOLD signal power and clinical features. Treatment response (responder vs. nonresponder) was predicted with 85-95% accuracy. Reduction in symptoms was predicted to within a mean error of ±16% (r = .68, p < .001). These preliminary findings suggest that therapeutic outcome to DLPFC-rTMS could be predicted at a clinically meaningful level using only a small number of core neurobiological features of MDD, warranting prospective testing to ascertain generalizability. This provides a novel, transparent and physiologically plausible multivariate approach for classification of individual response to what has become the most commonly employed rTMS treatment worldwide. This study utilizes data from a larger clinical study (Australian New Zealand Clinical Trials Registry: Investigating Predictors of Response to Transcranial Magnetic Stimulation for the Treatment of Depression; ACTRN12610001071011; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=336262).

Chronic Prostatitis and/or Chronic Pelvic Pain as a Psychoneuromuscular Disorder-A Meta-analysis.

OBJECTIVE: To evaluate effectiveness of physical therapy, biofeedback, and/or cognitive behavioral therapy for chronic prostatitis/chronic pelvic pain syndrome (CP and/or CPPS). This symptom complex has resisted resolution from conventional urologic treatment of the prostate, which includes antibiotics, alpha-blockers, and analgesics. Beginning in 1995, a new paradigm was introduced viewing CP and/or CPPS as a psychoneuromuscular disorder driven by protective pelvic floor guarding and psychosocial stress. METHODS: A literature search (PubMed, Google Scholar, and the Cochran Library) was conducted from inception through December 2017 using key words related to CP and/or CPPS (eg, prostatitis and pelvic pain) with physical therapy (eg, myofascial trigger point release) and/or biofeedback or cognitive behavioral treatment. Studies were required to include pre- and post-treatment with the National Institutes of Health Chronic Prostatitis Symptom Index (CPSI) scores. RESULTS: Eight studies inclusive of 280 patients met primary inclusion criteria. Study sample sizes ranged from 8 to 116 men (mean = 35); treatment duration ranged from 8 to 26 weeks (mean = 14). Pretreatment mean CPSI scores ranged from 21.7 to 33.5. The nonstandardized weighted mean reduction of CPSI score from baseline was 8.8 points; 95% confidence interval (7.5, 11.1); P <.001. The I2 statistic = 18.5% indicating little heterogeneity between studies. A sensitivity analysis including an additional multimodal intervention study of with 100 patients produced similar findings. CONCLUSION: Conventional medical treatment often fails to resolve CP and/or CPPS. A 6-point reduction in CPSI score is considered a clinically meaningful improvement of symptoms. This meta-analysis shows that treating CP and/or CPPS as a psychoneuromuscular disorder can significantly exceed this clinical threshold.

Occipital bending in schizophrenia.

OBJECTIVE: To investigate the prevalence of occipital bending (an occipital lobe crossing or twisting across the midline) in subjects with schizophrenia and matched healthy controls. METHOD: Occipital bending prevalence was investigated in 37 patients with schizophrenia and 44 healthy controls. RESULTS: Ratings showed that prevalence was nearly three times higher among schizophrenia patients (13/37 [35.1%]) than in control subjects (6/44 [13.6%]). Furthermore, those with schizophrenia had greater normalized gray matter volume but less white matter volume and had larger brain-to-cranial ratio. CONCLUSION: The results suggest that occipital bending is more prevalent among schizophrenia patients than healthy subjects and that schizophrenia patients have different gray matter-white matter proportions. Although the cause and clinical ramifications of occipital bending are unclear, the results infer that occipital bending may be a marker of psychiatric illness.

Repetitive transcranial magnetic stimulation for treatment resistant depression: Re-establishing connections.

Repetitive transcranial magnetic stimulation (rTMS) is a relatively recent addition to the neurostimulation armamentarium for treating individuals suffering from treatment refractory depression and has demonstrated efficacy in clinical trials. One of the proposed mechanisms of action underlying the therapeutic effects of rTMS for depression involves the modulation of depression-associated dysfunctional activity in distributed brain networks involving frontal cortical and subcortical limbic regions, via changes to aberrant functional and structural connectivity. Although there is currently a paucity of published data, we review changes to functional and structural connectivity following rTMS for depression. Current evidence suggests an rTMS-induced normalisation of depression-associated dysfunction within and between large scale functional networks, including the default mode, central executive and salience networks, associated with an amelioration of depressive symptoms. Additionally, changes to measures of white matter microstructure, primarily in the dorsolateral prefrontal cortex, have also been reported following rTMS for depression, possibly reversing depression-associated abnormalities. We argue that measures of functional and structural connectivity can be used to optimise rTMS targeting within the dorsolateral prefrontal cortex and also to explore novel rTMS targets for depression. Finally, we discuss the utility of measures of brain connectivity as predictive biomarkers of rTMS treatment response in guiding therapeutic decisions.

A STUDY OF THE PATTERN OF RESPONSE TO rTMS TREATMENT IN DEPRESSION.

BACKGROUND: Considerable research has demonstrated the efficacy of repetitive transcranial magnetic stimulation (rTMS) treatment in patients with depression. However, limited research has described the pattern of response to rTMS treatment or explored possible predictors of the likelihood of treatment response. METHODS: Data from 11 clinical trials (n = 1,132) was pooled and we described the pattern of response to rTMS, rate of response, and remission as well as potential clinical and demographic predictors of response. RESULTS: There was a bimodal pattern of response to rTMS with the response-associated peak at 57% reduction in depression rating scale scores. About 46% of patients achieved response criteria, with 31% completing rTMS treatment in remission. A greater likelihood of response was seen for patients who had less severe depression at baseline, a shorter duration of the current episode, and recurrent rather than single episode of depression. Greater response was also seen in patients treated at higher stimulation intensity. CONCLUSIONS: A meaningful percentage (>40%) of patients respond to a course of rTMS treatment. Response does vary with a number of clinical and demographic variables but none of these variables exert a sufficiently strong influence on response rates to warrant using these criteria to exclude patients from treatment.

Equal Improvement in Men and Women in the Treatment of Urologic Chronic Pelvic Pain Syndrome Using a Multi-modal Protocol with an Internal Myofascial Trigger Point Wand.

Both men and women require treatment for urologic chronic pelvic pain syndromes (UCPPS), which includes interstitial cystitis/painful bladder syndrome, pelvic floor dysfunction, and chronic prostatitis/chronic pelvic pain syndrome. However, it is unknown if men and women respond differently to a protocol that includes specific physical therapy self-treatment using an internal trigger point wand and training in paradoxical relaxation. We performed a retrospective analysis by gender in a single arm, open label, single center clinical trial designed to evaluate the safety and effectiveness of a protocol for the treatment of UCPPS from October, 2008 to May, 2011. 314 adult men (79.9 %) and 79 (20.1 %) women met inclusion criteria. The median duration of symptoms was 60 months. The protocol required an initial 6-day clinic for training followed by a 6-month self-treatment period. The treatment included self-administered pelvic floor trigger point release with an internal trigger point device for physical therapy along with paradoxical relaxation training. Notable gender differences in prior treatments were observed. Men had a lower median [Interquartile Range] NIH-CPSI score at baseline than women (27 [21, 31] vs. 29 [22, 33], p = 0.04). Using a 1-10 scale with 10 = Most Severe, the median reduction in trigger point sensitivity was 3 units for both men and women after 6 months therapy (p = 0.74). A modified Intention to Treat analysis and a multivariate regression analysis found similar results. We conclude that men and women have similar, significant reductions in trigger point sensitivity with this protocol.

Chronic pelvic pain syndrome: reduction of medication use after pelvic floor physical therapy with an internal myofascial trigger point wand.

This study documents the voluntary reduction in medication use in patients with refractory chronic pelvic pain syndrome utilizing a protocol of pelvic floor myofascial trigger point release with an FDA approved internal trigger point wand and paradoxical relaxation therapy. Self-referred patients were enrolled in a 6-day training clinic from October, 2008 to May, 2011 and followed the protocol for 6 months. Medication usage and symptom scores on a 1-10 scale (10 = most severe) were collected at baseline, and 1 and 6 months. All changes in medication use were at the patient's discretion. Changes in medication use were assessed by McNemar's test in both complete case and modified intention to treat (mITT) analyses. 374 out of 396 patients met inclusion criteria; 79.7 % were male, median age of 43 years and median symptom duration of 5 years. In the complete case analysis, the percent of patients using medications at baseline was 63.6 %. After 6 months of treatment the percentage was 40.1 %, a 36.9 % reduction (p < 0.001). In the mITT analysis, there was a 22.7 % overall reduction from baseline (p < 0.001). Medication cessation at 6 months was significantly associated with a reduction in total symptoms (p = 0.03).

Occipital bending (Yakovlevian torque) in bipolar depression.

Differing levels of occipital lobe asymmetry and enlarged lateral ventricles have been reported within patients with bipolar disorder (BD) compared with healthy controls, suggesting different rates of occipital bending (OB). This may exert pressure on subcortical structures, such as the hippocampus, reduced among psychiatric patients. We investigated OB prevalence in 35 patients with BD and 36 healthy controls, and ventricular and occipital volumes. Prevalence was four times higher among BD patients (12/35 [34.3%]) than in control subjects (3/36 [8.3%]), as well as larger lateral ventricular volumes (LVVs). Furthermore, we found OB to relate to left-to-right ventricular and occipital lobe volume (OLV) ratios. Those with OB also had reduced left-to-right hippocampal volume ratios. The results suggest that OB is more common among BD patients than healthy subjects, and prevalent in both BD Type I and Type II patients. We posit that anomalies in neural pruning or ventricular enlargement may precipitate OB, consequently resulting in one occipital lobe twisting around the other. Although the clinical implications of these results are unclear, the study suggests that asymmetrical ventricular volume matched with a pattern of oppositely asymmetrical occipital volume is related to OB and may be a marker of psychiatric illness.

Occipital bending in depression.

There are reports of differences in occipital lobe asymmetry within psychiatric populations when compared with healthy control subjects. Anecdotal evidence and enlarged lateral ventricles suggests that there may also be a different pattern of curvature whereby one occipital lobe wraps around the other, termed 'occipital bending'. We investigated the prevalence of occipital bending in 51 patients with major depressive disorder (males mean age = 41.96 ± 14.00 years, females mean age = 40.71 ± 12.41 years) and 48 age- and sex-matched healthy control subjects (males mean age = 40.29 ± 10.23 years, females mean age = 42.47 ± 14.25 years) and found the prevalence to be three times higher among patients with major depressive disorder (18/51, 35.3%) when compared with control subjects (6/48, 12.5%). The results suggest that occipital bending is more common among patients with major depressive disorder than healthy subjects, and that occipital asymmetry and occipital bending are separate phenomena. Incomplete neural pruning may lead to the cranial space available for brain growth being restricted, or ventricular enlargement may exacerbate the natural occipital curvature patterns, subsequently causing the brain to become squashed and forced to 'wrap' around the other occipital lobe. Although the clinical implications of these results are unclear, they provide an impetus for further research into the relevance of occipital bending in major depression disorder.

OnabotulinumtoxinA office treatment for neurogenic bladder incontinence in Parkinson's disease.

OBJECTIVE: To evaluate safety and effectiveness of low-dose (100 U) onabotulinumtoxinA (onabotA) bladder injections as an office procedure with topical anesthesia only for patients with Parkinson's disease (PD) and incontinence. METHODS: Qualified patients who failed oral antimuscarinic agents participated in an open-label study. They discontinued antimuscarinics, provided a King's Health Questionnaire (KHQ), voiding symptom score, and 3-day voiding diary. Free uroflowmetry with post-void ultrasounds and cystometrogram pressure/flow studies were performed. Patients underwent flexible cystoscopy and injections of onabotA 100 U (10 U/mL) dispersed into 10-20 submucosal/detrusor sites of the bladder, including the trigone. Voiding diaries, questionnaires, and free uroflowmetry with post-void ultrasound residual urine measurements were repeated after 1, 3, and 6 months. RESULTS: Twelve men and 8 women were treated: mean age, 70.4 years; duration of disease, 10.6 years; median bladder contraction volume, 115 mL; maximum bladder pressure, 62 cm; and post-void volume, 9 mL. Moderate to marked symptom relief at 3 months and a 50% incontinence decrease over 6 months relative to pretreatment was reported in 59% patients (P ≤.02); 5 patients failed to complete the 6-month endpoint. No urinary retention required catheterization. CONCLUSION: Office cystoscopy with low-dose onabotA injection treatment is a potential long-term management strategy for patients with PD and urinary incontinence who fail oral antimuscarinic agents. The treatment seems to be safely utilized for older men with BPH as well as women with potential hypoactive detrusor function.

Randomized multicenter feasibility trial of myofascial physical therapy for the treatment of urological chronic pelvic pain syndromes.

PURPOSE: We determined the feasibility of conducting a randomized clinical trial designed to compare 2 methods of manual therapy (myofascial physical therapy and global therapeutic massage) in patients with urological chronic pelvic pain syndromes. MATERIALS AND METHODS: We recruited 48 subjects with chronic prostatitis/chronic pelvic pain syndrome or interstitial cystitis/painful bladder syndrome at 6 clinical centers. Eligible patients were randomized to myofascial physical therapy or global therapeutic massage and were scheduled to receive up to 10 weekly treatments of 1 hour each. Criteria to assess feasibility included adherence of therapists to prescribed therapeutic protocol as determined by records of treatment, adverse events during study treatment and rate of response to therapy as assessed by the patient global response assessment. Primary outcome analysis compared response rates between treatment arms using Mantel-Haenszel methods. RESULTS: There were 23 (49%) men and 24 (51%) women randomized during a 6-month period. Of the patients 24 (51%) were randomized to global therapeutic massage, 23 (49%) to myofascial physical therapy and 44 (94%) completed the study. Therapist adherence to the treatment protocols was excellent. The global response assessment response rate of 57% in the myofascial physical therapy group was significantly higher than the rate of 21% in the global therapeutic massage treatment group (p = 0.03). CONCLUSIONS: We judged the feasibility of conducting a full-scale trial of physical therapy methods and the preliminary findings of a beneficial effect of myofascial physical therapy warrants further study.

Deep brain stimulation for treatment-resistant depression: efficacy, safety and mechanisms of action.

Deep brain stimulation (DBS), a neuromodulation therapy that has been used successfully in the treatment of symptoms associated with movement disorders, has recently undergone clinical trials for individuals suffering from treatment-resistant depression (TRD). Although the small patient numbers and open label study design limit our ability to identify optimum targets and make definitive conclusions about treatment efficacy, a review of the published research demonstrates significant reductions in depressive symptomatology and high rates of remission in a severely treatment-resistant patient group. Despite these encouraging results, an incomplete understanding of the mechanisms of action underlying the therapeutic effects of DBS for TRD is highlighted, paralleling the incomplete understanding of the neuroanatomy of mood regulation and treatment resistance. Proposed mechanisms of action include short and long-term local effects of stimulation at the neuronal level, to modulation of neural network activity.

Sacral nerve stimulator revision due to somatic growth.

PURPOSE: Sacral nerve modulation is a Food and Drug Administration approved treatment for refractory urgency, frequency, urge incontinence and nonobstructive urinary retention in adults. The sparse literature on sacral nerve modulation in children focuses on its initial efficacy in patients with neurogenic bladder and dysfunctional elimination. We describe our initial experience with sacral nerve modulation and the phenomenon of growth spurts associated with lead malfunction that necessitates revision. MATERIALS AND METHODS: After receiving institutional review board approval we retrospectively reviewed the charts of pediatric patients who underwent sacral nerve modulation surgery at our institution. Charts were examined for patient demographics, subjective success, the need for further surgery and success after revision. RESULTS: Four patients underwent sacral nerve modulation at an average age of 12.1 years. All patients reported initial success, defined as greater than 50% symptom improvement. Subsequently 3 patients required a total of 5 revisions due to lead malfunction with an average of 1.5 years between surgeries. In those requiring revision the average somatic growth between revisions was 8.1 cm. Return of efficacy was reported after each revision. All patients had functioning nerve stimulators in place and continued to have a positive subjective response. CONCLUSIONS: The sparse data on sacral nerve modulation in children shows efficacy and safety similar to those in adults. Somatic growth may be associated with lead malfunction and require surgical revision. We report a small series showing that revision can be done successfully and safely. Informed consent for sacral nerve modulation in pediatric patients should include a discussion of somatic growth as a possible cause of lead malfunction necessitating revision.

Safety and effectiveness of an internal pelvic myofascial trigger point wand for urologic chronic pelvic pain syndrome.

OBJECTIVES: Pelvic muscle tenderness occurs often in patients with urologic chronic pelvic pain syndrome; symptoms frequently can be reduced with pelvic myofascial physical therapy. This open-label pilot study evaluated the safety of a personal wand that enables patient's self-treatment of internal myofascial trigger points in the pelvic floor and its effect in reducing pelvic muscle tenderness. METHODS: A specially designed curved wand served as an extended finger to locate and release painful internal myofascial trigger points; an integrated algometer monitors and guides appropriate applied point pressure. Patients used the wand several times weekly after education and careful supervision. Evaluations for adverse events and assessments of pain sensitivity were conducted at 1 and 6 months after commencing use. RESULTS: One hundred and thirteen of the enrolled 157 patients completed 6 months of wand use-106 men and 7 women; 44 patients withdrew before study completion but none for adverse events. Median age was 41 years and 93% were male. Baseline median sensitivity visual analog scale score (1 to 10, 10=most sensitive) was 7.5 and decreased significantly at 6 months to 4 (P<0.001, Wilcoxon matched-pairs signed-rank test). Most patients (95.5%) reported the wand as either very or moderately effective in alleviating pain. No serious adverse events occurred. CONCLUSIONS: A multimodal protocol using an internal pelvic therapeutic wand seems to be a safe, viable treatment option in select refractory patients with pelvic pain.

6-day intensive treatment protocol for refractory chronic prostatitis/chronic pelvic pain syndrome using myofascial release and paradoxical relaxation training.

PURPOSE: Chronic prostatitis/chronic pelvic pain syndrome continues to elude conventional therapy. Evidence supports the concept that phenotypes of pelvic muscular tenderness and psychosocial distress respond to myofascial trigger point release and specific relaxation training. This case series reports long-term outcomes of a 6-day intensive combination of such therapies in refractory cases. MATERIALS AND METHODS: A total of 200 men with pain for a median of 4.8 years referred themselves to Stanford University Urology for participation in an established protocol. Daily 3 to 5-hour sessions including intrapelvic/extrapelvic physiotherapy, self-treatment training and paradoxical relaxation training provided a solid introduction to facilitate self-management. Subjects answered baseline and followup questionnaires at variable intervals after initiation of therapy including the National Institutes of Health Chronic Prostatitis Symptom Index, global response assessment and a psychological query. RESULTS: We followed 116 men for a median of 6 months. Baseline total symptom index was 26 out of a maximum 43 points. Scores decreased by 30% (p <0.001) at followup with 60% of subjects demonstrating a 6-point or greater decrease (range 6 to 30). Domains of pain, urinary dysfunction and quality of life showed significant improvement (p <0.001). Global response assessment revealed that 82% of subjects reported improvement (59% marked to moderate, 23% slight). CONCLUSIONS: Men with chronic pelvic pain refractory to traditional treatment benefit from intensive myofascial trigger point therapy and concomitant paradoxical relaxation training. Education in techniques for self-administered trigger point release and continued pelvic muscle relaxation help patients reduce pain and dysfunction. Refinement of clinical phenotyping and selection of patients with pelvic muscle tenderness should enhance the success rate with this treatment modality.