cssi/SciSciGPT-SciSciNet huggingface dataset:
Structurally diverse c-Myc inhibitors share a common mechanism of action involving ATP depletion

// Huabo Wang 1 , Lokendra Sharma 1 , Jie Lu 1 , Paul Finch 1 , Steven Fletcher 2,3 and Edward V. Prochownik 1,4,5 1 Division of Hematology/Oncology, Children’s Hospital of Pittsburgh of University of Pittsburgh Medical Center, Pittsburgh PA, USA 2 Department of Pharmaceutical Sciences, The University of Maryland School of Pharmacy, Baltimore, MD, USA 3 The Greenebaum Cancer Center, Baltimore MD, USA 4 Department of Microbiology and Molecular Genetics, The University of Pittsburgh, Pittsburgh, PA, USA 5 The University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA Correspondence to: Edward V. Prochownik, email: // Keywords : 10058-F4, 10074-G5, JQ1, artemisinin, glycolysis Received : March 31, 2015 Accepted : April 10, 2015 Published : May 30, 2015 Abstract The c-Myc (Myc) oncoprotein is deregulated in a large proportion of diverse human cancers. Considerable effort has therefore been directed at identifying pharmacologic inhibitors as potential anti-neoplastic agents. Three such groups of small molecule inhibitors have been described. The first is comprised of so-called “direct” inhibitors, which perturb Myc’s ability to form productive DNA-binding heterodimers in association with its partner, Max. The second group is comprised of indirect inhibitors, which largely function by targeting the BET-domain protein BRD4 to prevent the proper formation of transcriptional complexes that assemble in response to Myc-Max DNA binding. Thirdly, synthetic lethal inhibitors cause the selective apoptosis of Myc over-expressing either by promoting mitotic catastrophe or altering Myc protein stability. We report here a common mechanism by which all Myc inhibitors, irrespective of class, lead to eventual cellular demise. This involves the depletion of ATP stores due to mitochondrial dysfunction and the eventual down-regulation of Myc protein. The accompanying metabolic de-regulation causes neutral lipid accumulation, cell cycle arrest, and an attempt to rectify the ATP deficit by up-regulating AMP-activated protein kinase (AMPK). These responses are ultimately futile due to the lack of functional Myc to support the requisite anabolic response. Finally, the effects of Myc depletion on ATP levels, cell cycle arrest, differentiation and AMPK activation can be mimicked by pharmacologic inhibition of the mitochondrial electron transport chain without affecting Myc levels. Thus, all Myc inhibitors promote a global energy collapse that appears to underlie many of their phenotypic consequences.
Amifostine pretreatment for protection against cyclophosphamide-induced and cisplatin-induced toxicities: results of a randomized control trial in patients with advanced ovarian cancer.

PURPOSESerious cumulative toxicity is a well-recognized consequence of chemotherapy. Amifostine, an organic thiophosphate, has demonstrated the ability to protect selectively a broad range of normal, but not neoplastic, tissues from the cytotoxic effects of chemotherapy and radiotherapy. This study was designed to determine if amifostine could reduce the serious toxicities associated with cyclophosphamide and cisplatin (CP), without reducing antitumor efficacy in patients with ovarian cancer.PATIENTS AND METHODSTwo hundred forty-two patients with advanced ovarian cancer were randomized to receive six cycles of cyclophosphamide (1,000 mg/m2) and cisplatin (100 mg/m2) with or without amifostine (910 mg/m2) every 3 weeks for six cycles. The occurrence of hematologic, renal, neurologic, and ototoxicity was evaluated. Antitumor efficacy was assessed by pathologic tumor response and survival.RESULTSPretreatment with amifostine before each cycle of chemotherapy resulted in a reduction of cumulative toxicities. H...
High incidence rates of invasive pneumococcal disease in the White Mountain Apache population.

• Objective.— In this article we determine the incidence and clinical spectrum of invasive pneumococcal disease in the White Mountain Apache population, a group known to have a high incidence of invasive disease due to Haemophilus influenzae type b. Design.— Patients from whom cultures of normally sterile body sites yielded Streptococcus pneumoniae were identified retrospectively through review of hospital laboratory records from a 6.8-year period. Clinical data were reviewed and incidence rates were computed. Setting.— The Whiteriver Indian Health Service Hospital is located on the 1.7-million-acre White Mountain Apache Reservation in eastern Arizona. Patients.— Approximately 10 000 members of the White Mountain Apache Tribe reside on or near the reservation and receive health care through the Whiteriver Indian Health Service Hospital. Outcome Measures.— The average annual incidence rates of invasive pneumococcal disease were calculated and clinical characteristics were reviewed. Results.— One hundred thirty-eight cases of invasive pneumococcal disease were identified. The average annual incidence rate was 207 per 100 000 population, and 156 per 100 000 population when adjusted for age by direct standardization to the 1988 US population. The incidence rate was highest in children between 1 and 2 years—2396 per 100000. The overall case-fatality rate was 5%. Pneumococcal pneumonia was the diagnosis in 79% of the patients 5 years of age or older. Alcohol abuse, identified in 66% of the cases in adults, was the most common underlying medical condition. Conclusion.— The incidence rates in White Mountain Apaches are the highest reported for any population. A vaccine effective in children would greatly benefit this population. ( Arch Intern Med . 1992;152:2277-2282)
Vortex: enabling cooperative selective wormholing for network security systems

We present a novel approach to remote traffic aggregation for Network Intrusion Detection Systems (NIDS) called Cooperative Selective Wormholing (CSW). Our approach works by selectively aggregating traffic bound for unused network ports on a volunteer's commodity PC. CSW could enable NIDS operators to cheaply and efficiently monitor large distributed portions of the Internet, something they are currently incapable of. Based on a study of several hundred hosts in a university network, we posit that there is sufficient heterogeneity in hosts' network service configurations to achieve a high degree of network coverage by re-using unused port space on client machines. We demonstrate Vortex, a proof-of-concept CSW implementation that runs on a wide range of commodity PCs (Unix and Windows). Our experiments show that Vortex can selectively aggregate traffic to a virtual machine backend, effectively allowing two machines to share the same IP address transparently. We close with a discussion of the basic requirements for a large-scale CSW deployment.
Total Knee Arthroplasty

Richard D. Scott. Philadelphia: Elsevier; 2006. 148 pages. $195.00. ISBN: 978-0-7216-3948-2. This brief yet concise text is the work of a real expert and pioneer in the field of total knee arthroplasty. The text, despite its brevity, covers the topic of total knee arthroplasty well. Typically, the chapters are minimally referenced; however, the author …
Critical Reflections on 4/29/1992 and Beyond

Jerry Kang (JK): It's hard to believe that it's been almost twenty years since what Koreans called Sa-I-Gu—4/29—when Los Angeles burned, and I'm excited about being able to have a conversation with some of my closest colleagues on the two decades having passed.
Tolerance sensitivity analysis in a variational design environment

This paper presents the use of variational geometry theory to calculate the tolerance sensitivities. Due to the lack of mathematical foundation, it has long been a difficult task to calculate how one design constraint variation will affect other constraints (tolerance sensitivity calculations). In the variational geometry–based design environment, design constraints are described with mathematical equations, and tolerances are considered as design constraint variations. Because of the solid mathematical foundation behind the variational geometry, both dimensional and geometric tolerances can be analytically studied, which provides a powerful tool for the variation reduction in vehicle design and manufacturing.
Pooling Issues and Methods in Regression Analysis with Examples in Marketing Research

The existence of multiple observations within several cross sections gives rise to both opportunities and problems in the application of regression analysis. In this article the issues associated w...
Human sex differences in solving a virtual navigation problem

The current study examined sex differences in initial and subsequent strategies in solving a navigational problem within a virtual reality environment. We tested 163 undergraduates on a virtual T-maze task that included probe trials designed to assess whether participants were responding using either a place or response strategy. Participants were also tested on a mental rotation task and memory of the details of the virtual room. There were no differences between the sexes in copying or recalling a map of the room or on first trial performance of the T-maze. However, at trial two, males show a significant advantage in solving the task, and approximately 80% of the males adopt a place strategy to solve the T-maze whereas females at that point showed no strategy preference. Across all testing, both males and females preferentially used a place strategy. We discuss how factors such as spatial priming affect strategy preferences and how such factors may differentially affect males and females.
The Basis for Estuarine Habitat Restoration and Nutrient Trading Schemes in the Clean Water Act

This paper examines how habitat restoration techniques, such as revitalizing shellfish beds and restoring wetlands, can be used as a way to clean estuarine waters from the effects of Nitrogen (N) pollution, and, in doing so, satisfy the statutory requirements and policy intent of the Clean Water Act (CWA). The CWA requires each state to produce a Total Maximum Daily Load (TMDL) report for bodies of water that are impacted by pollutants, as well as a remediation plan. This report begins by identifying a specific variety of pollution, the scale of the problem, and the extent to which the pollutants must be reduced. In addition, strategies are identified to accomplish the goal of pollutant reduction. Since the 1990s, research has demonstrated the ability of oysters and other shellfish to filter the water column and therefore remove the effects of over-nitrification in coastal and estuarine waters. Other research has shown that wetland restoration can be used as a denitrification tool as well. Both these strategies use natural processes and have the benefits of not only removing nitrogen and its effects but also can provide benefits such as stimulating the regrowth of valuable eelgrass beds and revitalizing finfish populations and crustacean nurseries. Both have the ultimate effect of providing not only clearer estuarine waters but also a potential source of sustainable food stocks. This paper discusses the feasibility of using shellfish and wetlands restoration as an integral part of an overall strategy for the removal of the effects of over-nitrification of estuarine waters in the TMDL process and argues that these tools meet both the statutory requirements CWA and its policy objectives of restoring water quality.
Knowledge Flows Within and Outside Alliance Scope: Theory and Evidence

We examine the role of alliance scope in influencing knowledge transfers between parent firms. Using patent data and a sample of R&D alliances, we find that the knowledge flows within the scope of ...
Paclitaxel plus carboplatin and concurrent radiation therapy for patients with locally advanced non-small cell lung cancer

Previously untreated patients with stages IIIA or IIIB non-small cell lung cancer entered this phase II study to evaluate the activity and toxicity of combined paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and carboplatin and concurrent radiation. Patients received paclitaxel 50 mg/m2/wk as a 1-hour infusion and carboplatin area under the concentration-time curve of 2/wk for 7 weeks with radiation to the primary tumor and regional lymph nodes (44 Gy) followed by a boost to the tumor (22 Gy). In addition, patients received two additional cycles of paclitaxel 200 mg/m2 and carboplatin (area under the concentration-time curve of 6) 3 weeks apart. From March 1995 to February 1996, 23 patients entered the study and their overall response rate (complete plus partial responses) was 82%. The major toxicity was esophagitis. Nine patients (45%) had experienced grades 3 or 4 esophagitis by the end of the 7-week concurrent phase. Seven of the nine patients recovered from the esophagitis within 2 weeks and received the additional two cycles of paclitaxel 200 mg/m2 and carboplatin (area under the concentration-time curve of 6). Only one patient (4%) had grade 4 pneumonitis; this patient also recovered within 2 weeks and received the final two doses of combined chemotherapy. Therapy with paclitaxel, carboplatin, and concurrent radiation is a promising treatment for patients with locally advanced non-small cell lung cancer; it has a high response rate and acceptable toxicity.
Managing the Exchange Rate in the Face of Volatile Capital Flows

Emerging market economies (EMEs) face continuing challenges in managing boom-bust capital flow cycles. Flows have become increasingly volatile, putting upward pressures on currencies during the boom, and creating dislocations during the bust. During 2008, flows to EMEs, which had peaked at $665 billion the previous year, plummeted to less than $170 billion, only to surge again in 2010 as the global recovery got underway. Following the US sovereign downgrade, capital flows to EMEs again dried up, then resumed, and they have been bouncing around quite a bit ever since. This volatility, moreover, is unlikely to be the exclusive result of country-specific factors in the recipient countries (pull factors), but likely reflects global forces to a significant degree, including the changing monetary policy in major source countries and risk-on-risk-off considerations. Debates have ensued about how emerging market countries should manage this capital flow volatility.
Clustering very large data sets with principal direction divisive partitioning

We present a method to cluster data sets too large to fit in memory, based on a Low-Memory Factored Representation (LMFR). The LMFR represents the original data in a factored form with much less memory, while preserving the individuality of each of the original samples. The scalable clustering algorithm Principal Direction Divisive Partitioning (PDDP) can use the factored form in a natural way to obtain a clustering of the original dataset.
Data Driven Computing with noisy material data sets

We formulate a Data Driven Computing paradigm, termed max-ent Data Driven Computing, that generalizes distance-minimizing Data Driven Computing and is robust with respect to outliers. Robustness is achieved by means of clustering analysis. Specifically, we assign data points a variable relevance depending on distance to the solution and on maximum-entropy estimation. The resulting scheme consists of the minimization of a suitably-defined free energy over phase space subject to compatibility and equilibrium constraints. Distance-minimizing Data Driven schemes are recovered in the limit of zero temperature. We present selected numerical tests that establish the convergence properties of the max-ent Data Driven solvers and solutions.
Hypoxia-Inducible Factor 1α Signaling Promotes Repair of the Alveolar Epithelium after Acute Lung Injury

During the acute respiratory distress syndrome, epithelial cells, primarily alveolar type (AT) I cells, die and slough off, resulting in enhanced permeability. ATII cells proliferate and spread onto the denuded basement membrane to reseal the barrier. Repair of the alveolar epithelium is critical for clinical recovery; however, mechanisms underlying ATII cell proliferation and spreading are not well understood. We hypothesized that hypoxia-inducible factor (HIF)1α promotes proliferation and spreading of ATII cells during repair after lung injury. Mice were treated with lipopolysaccharide or hydrochloric acid. HIF activation in ATII cells after injury was demonstrated by increased luciferase activity in oxygen degradation domain–Luc (HIF reporter) mice and expression of the HIF1α target gene GLUT1. ATII cell proliferation during repair was attenuated in ATII cell–specific HIF1α knockout (SftpcCreERT2+/−;HIF1αf/f) mice. The HIF target vascular endothelial growth factor promoted ATII cell proliferation in vitro and after lung injury in vivo. In the scratch wound assay of cell spreading, HIF stabilization accelerated, whereas HIF1α shRNA delayed wound closure. SDF1 and its receptor, CXCR4, were found to be HIF1α-regulated genes in ATII cells and were up-regulated during lung injury. Stromal cell-derived factor 1/CXCR4 inhibition impaired cell spreading and delayed the resolution of permeability after lung injury. We conclude that HIF1α is activated in ATII cells after lung injury and promotes proliferation and spreading during repair.
Macrophage heme oxygenase-1-SIRT1-p53 axis regulates sterile inflammation in liver ischemia-reperfusion injury

Background & Aims Hepatic ischemia-reperfusion injury (IRI), characterized by exogenous antigen-independent local inflammation and hepatocellular death, represents a risk factor for acute and chronic rejection in liver transplantation. We aimed to investigate the molecular communication involved in the mechanism of liver IRI. Methods We analyzed human liver transplants, primary murine macrophage cell cultures and IR-stressed livers in myeloid-specific heme oxygenase-1 (HO-1) gene mutant mice, for anti-inflammatory and cytoprotective functions of macrophage-specific HO-1/SIRT1 (sirtuin 1)/p53 (tumor suppressor protein) signaling. Results Decreased HO-1 expression in human post-reperfusion liver transplant biopsies correlated with a deterioration in hepatocellular function (serum ALT; p p p p In vitro macrophage cultures revealed that HO-1 induction positively regulated SIRT1 signaling, whereas SIRT1-induced Arf inhibited ubiquitinating activity of MDM2 against p53, which in turn attenuated macrophage activation. In a murine model of hepatic warm IRI, myeloid-specific HO-1 deletion lacked SIRT1/p53, exacerbated liver inflammation and IR-hepatocellular death, whereas adjunctive SIRT1 activation restored p53 signaling and rescued livers from IR-damage. Conclusion This bench-to-bedside study identifies a new class of macrophages activated via the HO-1–SIRT1–p53 signaling axis in the mechanism of hepatic sterile inflammation. This mechanism could be a target for novel therapeutic strategies in liver transplant recipients. Lay summary Post-transplant low macrophage HO-1 expression in human liver transplants correlates with reduced hepatocellular function and survival. HO-1 regulates macrophage activation via the SIRT1–p53 signaling network and regulates hepatocellular death in liver ischemia-reperfusion injury. Thus targeting this pathway in liver transplant recipients could be of therapeutic benefit.
mRNA In Situ Hybridization of TIGR/MYOC in Human Trabecular Meshwork

PURPOSE: To determine the distribution of mRNA expression of the trabecular meshwork-induced glucocorticoid response protein/myocilin (TIGR/MYOC) in human trabecular meshwork. METHODS: In situ hybridization using a 1.25-kb probe obtained from reverse transcription-polymerase chain reaction of TIGR/MYOC cDNA was performed to determine the location of cell labeling within the different regions of the meshwork. The effect of dexamethasone on the pattern of labeling was studied in organ cultured meshwork. Trabecular meshwork from three sources was studied: enucleated eyes obtained at autopsy, trabeculectomy specimens obtained during filtration surgery, and meshworks from anterior segments in perfusion organ culture. Hybridization was performed on frozen sections, paraffin sections, and sections from JB-4 plastic-embedded tissue. RESULTS: Labeling for TIGR/MYOC mRNA was present in most trabecular cells of the uveal, corneoscleral, and juxtacanalicular regions but only variably present in the endothelial cells of Schlemm's canal. A similar pattern was found in the trabeculectomy specimens from eyes with primary open-angle or pseudoexfoliative glaucoma. Dexamethasone treatment increased the labeling intensity and number of labeled cells in meshwork, and also the number of labeled endothelial cells of Schlemm's canal. Fresh tissue processed within 12 hours postmortem gave more consistent labeling than older tissue, although some label was found up to 48 hours postmortem. Labeling was found in tissue from all three sources, and with all three embedding techniques; JB-4 sections provided the best morphologic resolution. CONCLUSIONS: In situ hybridization reveals that mRNA expression for TIGR/MYOC is present in most cells in all regions of the meshwork but only variably present in the endothelial cells of Schlemm's canal. Dexamethasone treatment increased the number and intensity of labeled cells, and also increased the number of labeled cells in the endothelial lining of Schlemm's canal.
Techniques of Ectopic Reservoir Placement and Their Pitfalls.

Abstract Background Ectopic placement of penile prosthesis reservoirs has become more common in patients whose space of Retzius has been compromised. Aim To describe techniques and instruments used to place penile prosthesis reservoirs ectopically. Methods We present our method of placing ectopic reservoirs and review the literature for other techniques. We also catalog the instruments used for this purpose. Outcomes Similar to traditional reservoir placement, successful ectopic reservoir implantation requires good cosmetic and functional success and low complication rates. Results Ectopic reservoir placement has been shown to be effective, to safely avoid bowel, bladder, and vascular injury, and to maintain excellent function and cosmesis. Multiple tools for ectopic placement have been described, but no data exist comparing their effectiveness and complications. Examples include dissection of the space anterior to the transversalis muscle using the surgeon's finger, a pediatric Yankauer suction tip, or a Foerster lung clamp. Instruments described to grasp and advance the reservoir include a sponge stick, a Foerster lung clamp, and the ectopic reservoir insertion tool (Sontec, Centennial, CO, USA). The effect of different instruments on the integrity of reservoir has not been extensively studied. Clinical Implications Attention to technique and the instruments used to dissect the ectopic space and grasp the reservoir are crucial to successful ectopic reservoir placement. Strengths and Limitations Reports of vascular, bowel, or bladder injuries during ectopic placement are exceedingly rare, as are reports of injury to reservoirs caused by traumatic grasping. However, no methods or tools have been compared in head-to-head trials. Conclusion Ectopic placement is safe and effective, but differences between methods and instruments have not been delineated. Thirumavalavan N, Gross MS, Munarriz R. Techniques of Ectopic Reservoir Placement and Their Pitfalls. J Sex Med 2017;14:1451–1454.
Self-reported tick-borne encephalitis (TBE) vaccination coverage in Europe: Results from a cross-sectional study

Adequate vaccination is effective in preventing tick-borne encephalitis (TBE). A population survey conducted in 2015 in Czech Republic, Estonia, Finland, Germany, Hungary, Latvia, Lithuania, Poland, Slovakia, Slovenia, and Sweden obtained information on TBE vaccination. Respondents answered 10 questions for themselves and household members. Data were weighted according to age and fine-tuned for geographical spread. Across the 10 countries (excluding Poland), TBE awareness was 83%; of all respondents, 68% were aware of TBE vaccines and 25% had ≥1 injections. Vaccination rates were lowest in Finland and Slovakia (∼10%), highest in Austria (85%, results from a separate 2015 survey), and varied widely in Germany. Across the 11 countries (excluding Austria), compliance with vaccination schedule among TBE-vaccinated respondents was 61%; 27% and 15% of respondents received first and second booster injections; strongest motivators for vaccination were fear of TBE (38%) and residence/spending time in high-risk areas (31-35%); main reasons for not receiving vaccination were beliefs that vaccination was unnecessary (33%) and that there was no risk of contracting TBE (23%). TBE vaccine uptake and compliance could be improved with effective public health information to increase TBE awareness and trust in vaccination and by updating recommendations to include all subjects visiting TBE-risk areas.
Biological connective tissues exhibit viscoelastic and poroelastic behavior at different frequency regimes: Application to tendon and skin biophysics.

Abstract In this study, a poroviscoelastic finite element model (FEM) was developed and used in conjunction with an AFM-based wide-bandwidth nanorheology system to predict the frequency-dependent mechanical behavior of tendon and dermis subjected to compression via nanoindentation. The aim was to distinguish between loading rates that are dominated by either poroelasticity, viscoelasticity, or the superposition of these processes. Using spherical probe tips having different radii, the force and tip displacement were measured and the magnitude, E ∗ , and phase angle, ϕ , of the dynamic complex modulus were evaluated for mouse supraspinatus tendon and mouse dermis. The peak frequencies of the phase angle were associated with the characteristic time constants of poroelastic and viscoelastic material behavior. The developed FE model could predict the separate poroelastic and viscoelastic responses of these soft tissues over a 4 decade frequency range, showing good agreement with experimental results. We observed that poroelasticity was the dominant energy dissipation mechanism for mouse dermis and supraspinatus tendon at higher indentation frequencies ( 10 2 to 10 4 Hz) whereas viscoelasticity was typically dominant at lower frequencies ( Statement of Significance Soft biological tissues exhibit complex, load- and time-dependent mechanical behavior. Evaluating their mechanical behavior requires sophisticated experimental tools and numerical models that can capture the fundamental mechanisms governing tissue function. Using an Atomic-force-microscopy-based rheology system and finite element models, the roles of the two most dominant time-dependent mechanisms (poroelasticity and viscoelasticity) that govern the dynamic loading behavior of mouse skin and tendon have been investigated. FE models were able to predict and quantify the contribution of each mechanism to the overall dynamic response and confirming the presence of these two distinct mechanisms in the mechanical response. Overall, these results provide novel insight into the viscoelastic and poroelastic properties of mouse skin and tendon and promote better understanding of the underlying origins of each mechanism.
Stereotactic Body Radiation Therapy for Prostate Cancer: An Institutional Experience Using MRI-guided Treatment Planning

With 222,500 new cases estimated for 2017, prostate cancer makes up approximately 10% of all new cancer diagnoses in the United States and is the third most common cancer after breast and lung cancer. In 2013, the American Society of Radiation Oncology (ASTRO) policy model recognized that stereotactic body radiation therapy (SBRT) may be used as an alternative to standard treatment modalities, i.e. intensity modulated radiation therapy (IMRT), to treat prostate cancer. In this study, we report outcomes for a cohort of 30 patients with prostate cancer treated with SBRT at our institution. We also describe, in detail, the technical aspects of SBRT planning and delivery for these patients, specifically the use of MRI in determining treatment volumes and detecting gross lesions. After institutional review board (IRB) approval, a retrospective analysis was done of 30 males with the diagnosis of prostate cancer treated in the Department of Radiation Oncology at the Baylor College of Medicine between January 2011 and June 2016. All patients received image-guided SBRT. Treatment planning was performed using a non-contrast computed tomography (CT) scan as well as a contrast thin-slice open MRI with the patient in the treatment position. Patient comparisons were done using the Mann-Whitney U, Fishers Exact, and Kaplan-Meier tests. Thirty patients were treated between January 2011 and June 2016. Twenty-six had follow-up data available and were included in the analysis. Median follow-up was 32 months (range 2-72 months). Mean and median ages at diagnosis were both 68.5 years. A total of 64% of the patients had foci on magnetic resonance imaging (MRI) or a palpable nodule on an exam. The median prostate-specific antigen (PSA) at diagnosis was 7.35 ng/mL (range 2.8-13), and the median PSA nadir after treatment was 0.4 ng/mL (range 0.01-4.5). The biochemical disease-free recurrence rate per Phoenix definition was 96%, with only one patient experiencing a biochemical recurrence four years after treatment. The patient with a recurrence was T2c, high-intermediate risk with a Gleason score of 7(3+4). He had a focus visible on MRI. Overall survival was 96%, with the only patient death unrelated to his prostate cancer. There was no statistical significance associated with recurrence and nodule on MRI (p=0.318), T-stage (p=0.222), Gleason score (p=0.890), risk group (p=0.654), age (p=0.692), or race (p=0.509). There were no grade three or four acute or long-term toxicities. SBRT of the prostate is an effective method for treating prostate cancer. We saw excellent PSA control and minimal acute or long-term toxicities after a median of three years of follow-up.
Being a Leader: Organizing a Health Services Research Program

Health services research (HSR) seeks to understand the factors that influence the need for healthcare services, the care delivered, its cost and quality, as well as the outcomes experienced. Organizing an HSR program requires leadership that leverages personnel, pre-existing infrastructure, and institutional resources. Key leadership principles include dedication to the mission of advancing surgical care through research and a strong commitment to the success of program members.
Scapular Winging in the Pediatric Patient.

Scapular winging is a rare condition that can lead to considerable functional impairment and cosmetic deformity but is frequently missed or misdiagnosed.Scapular winging is of particular concern in the pediatric patient given its association with birth injuries, perinatal thoracic operations, inheri
Optimizando la experiencia de ocio después de los 40

Aging is a natural process that occurs across the lifespan, but to suggest that some people age more successfully than others is to invoke some criteria of living well in later life and then to consider the factors that may contribute. This article puts leisure front and center in the aging process, especially after midlife, and identifies experiential aspects of leisure that may be most influential. But it departs from some of the standard models of successful aging in recognizing opportunities and possibilities even for those with disabling conditions, in reaching back earlier in adulthood for critical incidents that may prove influential, and in considering disengagement as well as engagement as processes and experiences for optimizing leisure and thus aging. Relying more on models of adaptation and selectivity from developmental psychologists Paul and Margaret Baltes and Leah Carstenson, social and civic engagement are considered as well.
Comfort-Centered Design of a Lightweight and Backdrivable Knee Exoskeleton

This letter presents design principles for comfort-centered wearable robots and their application in a lightweight and backdrivable knee exoskeleton. The mitigation of discomfort is treated as mechanical design and control issues and three solutions are proposed in this letter: 1) a new wearable structure optimizes the strap attachment configuration and suit layout to ameliorate excessive shear forces of conventional wearable structure design; 2) rolling knee joint and double-hinge mechanisms reduce the misalignment in the sagittal and frontal plane, without increasing the mechanical complexity and inertia, respectively; 3) a low impedance mechanical transmission reduces the reflected inertia and damping of the actuator to human, thus the exoskeleton is highlybackdrivable. Kinematic simulations demonstrate that misalignment between the robot joint and knee joint can be reduced by 74% at maximum knee flexion. In experiments, the exoskeleton in the unpowered mode exhibits 1.03 Nm root mean square (RMS) low resistive torque. The torque control experiments demonstrate 0.31 Nm RMS torque tracking error in three human subjects.
The Self-Regulated Learning Guide: Teaching Students to Think in the Language of Strategies

The Self-Regulated Learning Guide introduces K-12 teachers to the basics of self-regulation. Highly practical and supported by cutting-edge research, this book offers a variety of techniques for seamlessly infusing self-regulated learning principles into the classroom and for nurturing students’ motivation to strategize, reflect, and succeed. Featuring clear explanations of the psychology of self-regulation, these nine chapters provide teachers with core concepts, realistic case scenarios, reflection activities, and more to apply SRL concepts to classroom activities with confidence.
Chapter 25 DnaJ homologs and protein transport

Abstract A variety of intracellular protein transport processes require or are stimulated by members of the evolutionarily conserved 70 kDa heat shock protein (HSP70) family and other unidentified factors. The ability of HSP70s to control protein folding and assembly is thought to be the basis for their role in protein transport. In Escherichia coli, genetic and biochemical evidence suggests that the unique bacterial HSP70, DnaK, does not act alone but functions in concert with two other heat shock proteins, DnaJ and GrpE, to mediate such protein folding and assembly. Complete and partial DnaJ homologs have now been identified in other bacterial species as well as in the yeast, Saccharomyces cerevisiae . Genetic evidence suggests a role in protein transport for three of the four yeast homologs. Based on the functional complex of DnaJ and DnaK in E. coli , we propose that DnaJ homologs will interact with HSP70s via an evolutionarily conserved 'J-region' to mediate protein folding and assembly reactions important for protein transport processes. It will be of great interest to determine if the unidentified factors that are required along with HSP70s for maximum stimulation of some transport processes correspond to DnaJ homologs.
Sim2Real Viewpoint Invariant Visual Servoing by Recurrent Control

Humans are remarkably proficient at controlling their limbs and tools from a wide range of viewpoints. In robotics, this ability is referred to as visual servoing: moving a tool or end-point to a desired location using primarily visual feedback. In this paper, we propose learning viewpoint invariant visual servoing skills in a robot manipulation task. We train a deep recurrent controller that can automatically determine which actions move the end-effector of a robotic arm to a desired object. This problem is fundamentally ambiguous: under severe variation in viewpoint, it may be impossible to determine the actions in a single feedforward operation. Instead, our visual servoing approach uses its memory of past movements to understand how the actions affect the robot motion from the current viewpoint, correcting mistakes and gradually moving closer to the target. This ability is in stark contrast to previous visual servoing methods, which assume known dynamics or require a calibration phase. We learn our recurrent controller using simulated data, synthetic demonstrations and reinforcement learning. We then describe how the resulting model can be transferred to a real-world robot by disentangling perception from control and only adapting the visual layers. The adapted model can servo to previously unseen objects from novel viewpoints on a real-world Kuka IIWA robotic arm. For supplementary videos, see: https://www.youtube.com/watch?v=oLgM2Bnb7fo
Sleep-related symptoms in patients with mild stroke.

Study Objectives:Treatable sleep-related conditions are frequent in stroke patients, although their prevalence across stroke types and ideal method for screening is not clear. The objectives of thi...
Multiple Myeloma in a Young Female Presenting with Neurological Symptoms

Background Multiple myeloma is overall the 14th most common malignancy but is rarely seen in those younger than 35 years. Those in the younger age group have been shown to have a more aggressive course but reportedly have had similar responses to treatment compared to older cohorts. Extramedullary plasmacytomas are discrete soft tissue masses of neoplastic monoclonal plasma cells that often occur in patients with multiple myeloma. Case This case entails a young female with new diagnosis of multiple myeloma and multiple extramedullary plasmacytomas presenting with neurological symptoms. She was treated with CyBorD regimen but was refractory and progressed. Treatment was changed to DCEP regimen, and daratumumab was added for primary refractory myeloma. The patient improved rapidly. Conclusion This is a unique case of multiple myeloma in a young female that had failed first-line treatment but responded to targeted therapy of daratumumab. It highlights that multiple myeloma may present atypically in young patients. More research is needed on appropriate initial diagnosis and treatment of patients in this age group.
Biomedical optics applications of advanced lasers and nonlinear optics.

Significance: 2019 SPIE Photonics West conference hosted over 5000 presentations. Some important presentations in the Industrial Laser, Laser Source and Application (LASE) and Optoelectronics, Photonic Materials and Devices (OPTO) sections of the SPIE Photonics West conference have a risk of being overlooked by the biomedical community despite their implications for the field of biophotonics. We review some recent advances in the area of development coherent radiation sources in the infrared (IR), ultraviolet (UV), and terahertz (THz) regimes. Aim: Recent advances in coherent radiation sources in the IR, deep UV, and THz regimes were outlined, and the importance of each presentation to one or more promising biomedical applications was assessed. Approach: Presentations and proceedings from the LASE and OPTO sections were reviewed for inclusion. Emphasis was placed on talks from the Nonlinear Frequency Generation and Conversion: Materials and Devices XVIII conference, and the Terahertz, RF, Millimeter, and Submillimeter-Wave Technology and Applications XII conference. Conference sections that directly focused on biomedical applications were excluded. Results: Enhanced IR supercontinuum generation with compact supercontinuum sources may allow for real-time biomarker detection and create new opportunities for imaging tissues using the third biological window (1600 to 1850 nm). Efficient methods to generate deep UV (200 to 260 nm) radiation allow for the study of biologically important molecules through techniques such as resonance Raman spectroscopy while avoiding fluorescence overlap. Likewise, novel and improved THz generation methods seek to bridge the “THz gap” that has previously limited biomedical applications. Conclusions: Advances in coherent radiation sources in the IR, UV, and THz regimes have created new opportunities for biomedical optics research.
MET: a magneto-inductive sensing based electric toothbrushing monitoring system

Electric toothbrushes are widely used for home oral care, but many users do not achieve desired hygiene results due to insufficient brushing coverage or incorrect brushing techniques. Existing electric toothbrushing monitoring systems fail to detect these issues because they cannot achieve fine-grained position tracking. In this paper, we present a novel electric toothbrushing monitoring system called MET that tracks brushing coverage for all the 15 surfaces of teeth and detects different types of incorrect brushing techniques. This design is inspired by our observation that the motor inside an electric toothbrush generates a unique magnetic field, which can serve as a reliable signal for position and orientation tracking. MET is the first system that tracks both the position and orientation of an unmodified electric motor using magnetic inductive sensing. Experiments with fourteen users show that the average toothbrushing surface recognition accuracy of MET is 85.3%. Moreover, MET is robust to user location changes and posture variations and does not require any training from the users. Experimental results also demonstrate our significant advantages over existing commercial systems.
Design and Evaluation of EV Drivetrain Clunk and Shuffle Management Control System

Vehicle drivetrains contain backlash and compliance, making it challenging to transmit torque to the wheels smoothly and rapidly. Due to the presence of this lash and compliance, any rapid changes in the actuator torque gives rise to the so-called clunk and shuffle phenomena, which degrade the drivability of the vehicle. Hence, the actuator torque has to be shaped so that clunk and shuffle are maintained at acceptable levels. In order to accomplish the shaping, we develop a switching control system that switches between the contact mode and the backlash mode, based on an estimation of the drivetrain state. The system includes a controller, which consists of a Butterworth precompensator and a lead feedback compensator in the contact mode and a bang-bang controller in the backlash mode. It also includes an estimator, which is designed as an Extended Kalman Filter. We apply the proposed approach in an EV drivetrain, and show using simulations that the control system is effective in delivering the driver demand quickly, while, at the same time, also mitigating the clunk and shuffle. Along the way, we introduce metrics that quantify the performance of the shaping system, from the point of view of smoothness, responsiveness, and intensity of clunk. Based on these metrics, we show that the performance of the proposed system compares favorably with that of a torque shaping strategy, which is applied in some of our current vehicles.
A Mixed Methods Evaluation of the Implementation of Asthma Care in Rural School-Based Telehealth Clinics

Background/Purpose: Telehealth-delivered school-based asthma care offers an opportunity to overcome typical barriers to providing asthma care to children compared to the traditional setting. Exploring the key components of care and internal and external factors affecting delivery may facilitate implementation of these programs, which have been shown to expand care. We used a dissemination and implementation science approach to characterize barriers and facilitators to asthma care in a telehealth-delivered school-based program available in over 50 South Carolina schools, of which 91% serve students who qualify for free or reduced lunch. Methods: …
Improving Assessment of Demand for Postpartum Tubal Ligation among Publicly Insured Women in Texas.

Abstarct Objective : To assess an alternative method for estimating demand for postpartum tubal ligation and evaluate reproductive trajectories of low-income women who did not obtain a desired procedure. Study Design : In a two-year cohort study of 1,700 publicly insured women who delivered at eight hospitals in Texas, we identified those who had an unmet demand for tubal ligation prior to discharge from the hospital. We classified unmet demand as explicit or prompted based on survey questions that included a prompt regarding whether the respondent would like to have had a tubal ligation at the time of delivery. We assessed persistence of demand for permanent contraception, contraceptive use, and repeat pregnancies among all study participants who wanted but did not get a postpartum procedure. Results : Some 426 women desired a postpartum tubal ligation; 219 (51%) obtained one prior to discharge. Among the 207 participants with unmet demand, 62 (30%) expressed an explicit preference for the procedure, while 145 (70%) were identified from the prompt. Most with unmet demand still wanted permanent contraception three months after delivery (156/184), but only 23 had obtained interval procedures. By 18 months, the probability of a woman with unmet demand conceiving a pregnancy that she would likely carry to term was 12.5% (95% C.I.: 8.3% - 18.5%). Conclusion : The majority of unmet demand for postpartum tubal ligation among publicly insured women in Texas was uncovered via a prompt and would not have been evident in clinical records or from consent forms. Women unable to obtain a desired procedure had a substantial chance of pregnancy within 18 months after delivery. Implications : Estimates of unmet demand for postpartum tubal ligation based on clinical records and consent forms likely underestimate desire for permanent contraception. Among low-income women in Texas, those with unmet demand for postpartum tubal ligation require improved access to effective contraception.
A refutation of pure conjecture

The present paper explores three interrelated topics in Popper's theory of science: (1) his view of conjecture, (2) the aim of science, and (3) his (never fully articulated) theory of meaning. Central to Popper's theory of science is the notion of conjecture. Popper writes as if scientists faced with a problem proceed to tackle it by conjecture, that is, by guesses uninformed by inferential considerations. This paper develops a contrast between guesses and educated guesses in an attempt to show that there is more to scientific conjecture than conjecture. The suggestion is made that some inductive considerations enter into the process of educated guessing or scientific conjecture in such a way that the ‘context of discovery’ cannot be sharply separated from the ‘context of justification’. This discussion leads to a tension between Popper's negative method of conjecture and his realism. Given Popper's (implicit) theory of meaning it seems Popper's epistemology (the conjecture and refutation method) is incompatible with his metaphysical realism.
A general model for resource allocation in utility computing

A utility computing problem is one in which a server (service provider) provides computing resources to clients (service receivers) whose jobs require the resources for processing. In this paper, we propose a general, decentralized and auction-based model for the server-to-clients resource allocation problem. This model combines a general class of queueing processes with a general class of “incentivecompatible” bidding mechanisms. Crucial to this model is the interplay between the nature of queueing costs and the nature of good bidding mechanisms. Insights on how such interplay contributes to the stability of the system can be helpful in guiding specific implementations in real-world applications. This decentralized and auction-based resource allocation model naturally induces a multi-player game, which is the principal object we study in this paper. We show the existence and uniqueness of Nash equilibrium under this general setting. We also present distributed update dynamics that converge to this unique Nash equilibrium. The distributed dynamics given here share the features of being secure and requiring little communications, thus, providing a practical scheme through which Nash equilibrium is reached.