Beta Burst-Driven Adaptive Deep Brain Stimulation Improves Gait Impairment and Freezing of Gait in Parkinson's Disease.

Background: Freezing of gait (FOG) is a debilitating symptom of Parkinson's disease (PD) that is often refractory to medication. Pathological prolonged beta bursts within the subthalamic nucleus (STN) are associated with both worse impairment and freezing behavior in PD, which are improved with deep brain stimulation (DBS). The goal of the current study was to investigate the feasibility, safety, and tolerability of beta burst-driven adaptive DBS (aDBS) for FOG in PD. Methods: Seven individuals with PD were implanted with the investigational Summit™ RC+S DBS system (Medtronic, PLC) with leads placed bilaterally in the STN. A PC-in-the-loop architecture was used to adjust stimulation amplitude in real-time based on the observed beta burst durations in the STN. Participants performed either a harnessed stepping-in-place task or a free walking turning and barrier course, as well as clinical motor assessments and instrumented measures of bradykinesia, OFF stimulation, on aDBS, continuous DBS (cDBS), or random intermittent DBS (iDBS). Results: Beta burst driven aDBS was successfully implemented and deemed safe and tolerable in all seven participants. Gait metrics such as overall percent time freezing and mean peak shank angular velocity improved from OFF to aDBS and showed similar efficacy as cDBS. Similar improvements were also seen for overall clinical motor impairment, including tremor, as well as quantitative metrics of bradykinesia. Conclusion: Beta burst driven adaptive DBS was feasible, safe, and tolerable in individuals with PD with gait impairment and FOG.

Preclinical studies of a PARP targeted, Meitner-Auger emitting, theranostic radiopharmaceutical for metastatic ovarian cancer.

Advanced ovarian cancer currently has few therapeutic options. Poly(ADP-ribose) polymerase (PARP) inhibitors bind to nuclear PARP and trap the protein-inhibitor complex to DNA. This work investigates a theranostic PARP inhibitor for targeted radiopharmaceutical therapy of ovarian cancer in vitro and PET imaging of healthy mice in vivo. METHODS: [77Br]RD1 was synthesized and assessed for pharmacokinetics and cytotoxicity in human and murine ovarian cancer cell lines. [76Br]RD1 biodistribution and organ uptake in healthy mice were quantified through longitudinal PET/CT imaging and ex vivo radioactivity measurements. Organ-level dosimetry following [76/77Br]RD1 administration was calculated using RAPID, an in-house platform for absorbed dose in mice, and OLINDA for equivalent and effective dose in human. RESULTS: The maximum specific binding (Bmax), equilibrium dissociation constant (Kd), and nonspecific binding slope (NS) were calculated for each cell line. These values were used to calculate the cell specific activity uptake for cell viability studies. The half maximal effective concentration (EC50) was measured as 0.17 (95 % CI: 0.13-0.24) nM and 0.46 (0.13-0.24) nM for PARP(+) and PARP(-) expressing cell lines, respectively. The EC50 was 0.27 (0.21-0.36) nM and 0.30 (0.22-0.41) nM for BRCA1(-) and BRCA1(+) expressing cell lines, respectively. When measuring the EC50 as a function of cellular activity uptake and nuclear dose, the EC50 ranges from 0.020 to 0.039 Bq/cell and 3.3-9.2 Gy, respectively. Excretion through the hepatobiliary and renal pathways were observed in mice, with liver uptake of 2.3 ± 0.4 %ID/g after 48 h, contributing to estimated absorbed dose values in mice of 19.3 ± 0.3 mGy/MBq and 290 ± 10 mGy/MBq for [77Br]RD1 and [76Br]RD1, respectively. CONCLUSION: [77Br]RD1 cytotoxicity was dependent on PARP expression and independent of BRCA1 status. The in vitro results suggest that [77Br]RD1 cytotoxicity is driven by the targeted Meitner-Auger electron (MAe) radiotherapeutic effect of the agent. Further studies investigating the theranostic potential, organ dose, and tumor uptake of [76/77Br]RD1 are warranted.

Community laboratories in the United States: BioMakerspaces for life science learning.

Informal learning environments play a critical role in science, technology, engineering, and mathematics learning across the lifespan and are consequential in informing public understanding and engagement. This can be difficult to accomplish in life science where expertise thresholds and logistics involved with handling biological materials can restrict access. Community laboratories are informal learning environments that provide access to the resources necessary to carry out pursuits using enabling biotechnologies. We investigate a group of these spaces in order to ascertain how this occurs-with specific attention to how material and intellectual resources are structured and shape learning. Using surveys and focus group interviews, we explore a group of these spaces located in the United States. We found that the spaces examined offer learning activities that are sufficiently scaffolded and flexible as to promote personalized and community-driven practice. We discuss these findings in relation to informal learning environment design and learning.

Women's Perceptions of HIV- and Sexuality-Related Stigma in Relation to PrEP: Qualitative Findings from the Masibambane Study, Durban, South Africa.

Daily oral pre-exposure prophylaxis (PrEP) offers effective HIV prevention. In South Africa, PrEP is publicly available, but use among young women remains low. We explored young women's perceptions of PrEP to inform a gender-focused intervention to promote PrEP uptake. Six focus group discussions and eight in-depth interviews exploring perceptions of PrEP were conducted with forty-six women not using PrEP, ages 18-25, from central Durban. Data were thematically analyzed using a team-based consensus approach. The study was conducted among likely PrEP users: women were highly-educated, with 84.8% enrolled in post-secondary education. Qualitative data revealed intersecting social stigmas related to HIV and women's sexuality. Women feared that daily PrEP pills would be confused with anti-retroviral treatment, creating vulnerability to misplaced HIV stigma. Women also anticipated that taking PrEP could expose them to assumptions of promiscuity from the community. To address these anticipated community-level reactions, women suggested community-facing interventions to reduce the burden on young women considering PrEP. Concerns around PrEP use in this group of urban, educated women reflects layered stigmas that may inhibit future PrEP use. Stigma-reducing strategies, such as media campaigns and educational interventions directed at communities who could benefit from PrEP, should re-frame PrEP as an empowering and responsible choice for young women.

Nursing practice and global refugee migration: initial impressions from an Intergovernmental-Academic Partnership.

AIM: This report from the field describes impressions of the initial impact of bilateral, multi-sectoral field-based activities undertaken to strengthen International Organization for Migration/United Nations Migration Agency and US-based nurses' capacity to address complex clinical, social and cultural challenges experienced by refugees in resettlement. Authors comment on the defined and thorough health assessment process that refugees go through prior to resettlement, and focus on the essential nursing role in the health assessment process and continuum of care. The development of the interdisciplinary and collaborative partnership is described as well as next steps to move the partnership forward. BACKGROUND: In 2017, International Organization for Migration/United Nations Migration Agency and the University of Minnesota, guided by experts from the United States Centers for Disease Control and Prevention, began a unique bilateral Intergovernmental-Academic partnership to enhance the health care of refugees. A key component was to strengthen nursing care of refugees through the standardization of clinical practice and nursing leadership. SOURCES OF EVIDENCE: Listening sessions, direct interaction between International Organization for Migration/United Nations Migration Agency and US-based refugee resettlement stakeholders, patterns in resettlement. CONCLUSION AND IMPLICATIONS FOR NURSING AND HEALTH POLICY: The report highlights the potential public health impact of a bilateral and collaborative initiative that develops and bridges key points in the migration and health trajectory of people with refugee status. Separated by geography, context and scope of work, health professionals in different roles in varied worldwide settings with a spectrum of resources may not fully understand the work of each other. Project activities were a platform through which US-based and internationally based nurses established mutuality, reciprocity and equity as partners. By strengthening systems and resources, the partnership reinforces the abilities of nurses who engage in this important work, to optimize health and wellbeing of people with refugee status.

Strengthening the science of addressing antimicrobial resistance: a framework for planning, conducting and disseminating antimicrobial resistance intervention research.

Antimicrobial resistance (AMR) has the potential to threaten tens of millions of lives and poses major global economic and development challenges. As the AMR threat grows, it is increasingly important to strengthen the scientific evidence base on AMR policy interventions, to learn from existing policies and programmes, and to integrate scientific evidence into the global AMR response.While rigorous evaluations of AMR policy interventions are the ideal, they are far from the current reality. To strengthen this evidence base, we describe a framework for planning, conducting and disseminating research on AMR policy interventions. The framework identifies challenges in AMR research, areas for enhanced coordination and cooperation with decision-makers, and best practices in the design of impact evaluations for AMR policies.This framework offers a path forward, enabling increased local and global cooperation, and overcoming common limitations in existing research on AMR policy interventions.

Feasibility of direct venous inoculation of the radiation-attenuated Plasmodium falciparum whole sporozoite vaccine in children and infants in Siaya, western Kenya.

PfSPZ Vaccine, composed of radiation-attenuated, aseptic, purified, cryopreserved Plasmodium falciparum sporozoites, is administered by direct venous inoculation (DVI) for maximal efficacy against malaria. A critical issue for advancing vaccines that are administered intravenously is the ability to efficiently administer them across multiple age groups. As part of a pediatric safety, immunogenicity, and efficacy trial in western Kenya, we evaluated the feasibility and tolerability of DVI, including ease of venous access, injection time, and crying during the procedure across age groups. Part 1 was an age de-escalation, dose escalation trial in children aged 13 months-5 years and infants aged 5-12 months; part 2 was a vaccine efficacy trial including only infants, using the most skilled injectors from part 1. Injectors could use a vein viewer, if needed. A total of 1222 injections (target 0.5 mL) were initiated by DVI in 511 participants (36 were 5-9-year-olds, 65 were 13-59-month-olds, and 410 infants). The complete volume was injected in 1185/1222 (97.0%) vaccinations, 1083/1185 (91.4%) achieved with the first DVI. 474/511 (92.8%) participants received only complete injections, 27/511 (5.3%) received at least one partial injection (<0.5 mL), and in 10/511 (2.0%) venous access was not obtained. The rate of complete injections by single DVI for infants improved from 77.1% in part 1 to 92.8% in part 2. No crying occurred in 51/59 (86.4%) vaccinations in 5-9-year-olds, 25/86 (29.1%) vaccinations in 13-59-month-olds and 172/1067 (16.1%) vaccinations in infants. Mean administration time ranged from 2.6 to 4.6 minutes and was longer for younger age groups. These data show that vaccination by DVI was feasible and well tolerated in infants and children in this rural hospital in western Kenya, when performed by skilled injectors. We also report that shipping and storage in liquid nitrogen vapor phase was simple and efficient. (Clinicaltrials.gov NCT02687373).

Study reporting quality among interventions to reduce antibiotic use is a barrier to evidence-informed policymaking on antimicrobial resistance: systematic review.

BACKGROUND: Countries are currently seeking evidence-informed policy options to address antimicrobial resistance (AMR). While rigorous evaluations of AMR interventions are the ideal, they are far from the current reality. Additionally, poor reporting and documentation of AMR interventions impede efforts to use evidence to inform future evaluations and policy interventions. OBJECTIVES: To critically evaluate reporting quality gaps in AMR intervention research. METHODS: To evaluate the reporting quality of studies, we conducted a descriptive synthesis and comparative analysis of studies that were included in a recent systematic review of government policy interventions aiming to reduce human antimicrobial use. Reporting quality was assessed using the SQUIRE 2.0 checklist of 18 items for reporting system-level interventions to improve healthcare. Two reviewers independently applied the checklist to 66 studies identified in the systematic review. RESULTS: None of the studies included complete information on all 18 SQUIRE items (median score = 10, IQR = 8-11). Reporting quality varied across SQUIRE items, with 3% to 100% of studies reporting the recommended information for each SQUIRE item. Only 20% of studies reported the elements of the intervention in sufficient detail for replication and only 24% reported the mechanism through which the intervention was expected to work. CONCLUSIONS: Gaps in the reporting of impact evaluations pose challenges for interpreting and replicating study results. Failure to improve reporting practice of policy evaluations is likely to impede efforts to tackle the growing health, social and economic threats posed by AMR.

The Minnesota Multiphasic Personality Inventory-2-RF in Treatment-Seeking Veterans with History of Mild Traumatic Brain Injury.

OBJECTIVE: This study examined the Minnesota Multiphasic Personality Inventory-Second Edition-Restructured Form (MMPI-2-RF) to better understand symptom presentation in a sample of treatment-seeking Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) Veterans with self-reported history of mild traumatic brain injury (mTBI). METHOD: Participants underwent a comprehensive clinical neuropsychological battery including performance and symptom validity measures and self-report measures of depressive, posttraumatic, and post-concussive symptomatology. Those with possible symptom exaggeration (SE+) on the MMPI-2-RF were compared with those without (SE-) with regard to injury, psychiatric, validity, and cognitive variables. RESULTS: Between 50% and 87% of participants demonstrated possible symptom exaggeration on one or more MMPI-2-RF validity scales, and a large majority were elevated on content scales related to cognitive, somatic, and emotional complaints. The SE+ group reported higher depressive, posttraumatic, and post-concussive symptomatology, had higher scores on symptom validity measures, and performed more poorly on neuropsychological measures compared with the SE- group. There were no group differences with regard to injury variables or performance validity measures. Participants were more likely to exhibit possible symptom exaggeration on cognitive/somatic compared with traditional psychopathological validity scales. CONCLUSIONS: A sizable portion of treatment-seeking OEF/OIF Veterans demonstrated possible symptom exaggeration on MMPI-2-RF validity scales, which was associated with elevated scores on self-report measures and poorer cognitive performance, but not higher rates of performance validity failure, suggesting symptom and performance validity are distinct concepts. These findings have implications for the interpretation of clinical data in the context of possible symptom exaggeration and treatment in Veterans with persistent post-concussive symptoms.

Management of asymptomatic neonates born in the setting of chorioamnionitis: a safety comparison of the well-baby and intensive care setting.

BACKGROUND: Evaluate the safety of a change in care setting for asymptomatic neonates born to mothers with chorioamnionitis from the neonatal intensive care unit to the well baby nursery.Local problem:The neonatal intensive care unit evaluation and management of babies born to mothers with chorioamionitis often involves separation of the mother-baby dyad and more invasive interventions. METHODS: A single-center pre/post-intervention study of neonates born from January 2011 to November 2016, comparing safety outcomes in the neonatal intensive care unit (pre-intervention) and well baby nursery (post-intervention), following initiation of a triage protocol. INTERVENTIONS: A protocolized, systematic change was done in the practice location. RESULTS: Groups were similar for time to first antibiotic administration, sepsis symptom development and positive blood cultures. Length of stay (median 73.5 vs 64.4 h, P=0.0192) and % of neonates with intravenous fluid exposure (50.4% vs 7.6%, P<0.0001) were lower in the post-intervention group. Exclusive breastfeeding rates improved (pre-7.3% vs post-46.1%, P<0.0001). CONCLUSIONS: Asymptomatic neonates born to mothers with chorioamnionitis were safely treated in a well baby nursery under the guidance of a protocol for triage, thereby reducing NICU exposure for these neonates.

The Duffy antigen receptor for chemokines regulates asthma pathophysiology.

BACKGROUND: The Duffy antigen receptor for chemokines (DARC) is an atypical receptor that regulates pro-inflammatory cytokines. However, the role of DARC in asthma pathophysiology is unknown. OBJECTIVE: To determine the role of DARC in allergic airways disease in mice, and the association between DARC single nucleotide polymorphisms (SNPs) and clinical outcomes in patients with asthma. METHODS: Mice with targeted disruption of the Darc gene (Darc∆E2 ) or WT mice were challenged over 3 weeks with house dust mite (HDM) antigen. Allergic airways disease was assessed 24 hours and 7 days following the final challenge. Additionally, associations between DARC SNPs and clinical outcomes were analysed in a cohort of poorly controlled asthmatics. RESULTS: Total airway inflammation following HDM did not differ between Darc∆E2 and WT mice. At 24 hours, Darc∆E2 mice had increased airway hyperresponsiveness; however, at 7 days airway hyperresponsiveness had completely resolved in Darc∆E2 but persisted in WT mice. In poorly controlled asthmatics, DARC SNPs were associated with worse asthma control at randomization and subsequent increased risk of healthcare utilization (odds ratio 3.13(1.37-7.27), P=.0062). CONCLUSIONS AND CLINICAL RELEVANCE: Our animal model and human patient data suggest a novel role for DARC in the temporal regulation in asthma pathophysiology and symptoms.

Emtonjeni-A Structural Intervention to Integrate Sexual and Reproductive Health into Public Sector HIV Care in Cape Town, South Africa: Results of a Phase II Study.

Integration of sexual and reproductive health within HIV care services is a promising strategy for increasing access to family planning and STI services and reducing unwanted pregnancies, perinatal HIV transmission and maternal and infant mortality among people living with HIV and their partners. We conducted a Phase II randomized futility trial of a multi-level intervention to increase adherence to safer sex guidelines among those wishing to avoid pregnancy and adherence to safer conception guidelines among those seeking conception in newly-diagnosed HIV-positive persons in four public-sector HIV clinics in Cape Town. Clinics were pair-matched and the two clinics within each pair were randomized to either a three-session provider-delivered enhanced intervention (EI) (onsite contraceptive services and brief milieu intervention for staff) or standard-of-care (SOC) provider-delivered intervention. The futility analysis showed that we cannot rule out the possibility that the EI intervention has a 10 % point or greater success rate in improving adherence to safer sex/safer conception guidelines than does SOC (p = 0.573), indicating that the intervention holds merit, and a larger-scale confirmatory study showing whether the EI is superior to SOC has merit.

Intra-operative monitoring of two facial muscles in hemifacial spasm surgery.

BACKGROUND: Hemifacial spasm (HFS) is a chronic facial nerve disorder characterized by spontaneous muscle contractions. Microvascular decompression (MVD) is the neurosurgical treatment of choice. Intraoperative neurophysiologic monitoring (IOM) during MVD can help determine when adequate decompression is performed. METHODS: MVD with IOM was performed on 16 patients with HFS that included recording the abnormal lateral spread response (LSR) in lower facial muscles, considered as neurophysiologic marker of HFS. Two lower facial muscles were monitored as opposed to a standard monitoring of a single muscle. RESULTS: All patients underwent preoperative thin cut MRI confirming the presence of neurovascular conflict. Patients underwent small retrosigmoid craniotomy and MVD. In 13 cases, the LSR guided the surgeon to continue MVD until the response was unobtainable from all recorded lower facial muscles. In four of those (30%), the LSR persisted on one of the recorded muscle and prompted further exploration and decompression until complete disappearance of LSR in all recorded muscles. In two cases, the LSR disappeared after dural opening and never recurred during the procedure, therefore the completion of MVD was based on non reappearance of LSR. In one case, the LSR persisted despite apparent complete decompression of the nerve. Fourteen patients had complete relief of their symptoms after surgery, one had partial improvement and the one with persistent LSR was unchanged. CONCLUSION: Evaluation of the LSR by monitoring of two lower facial muscles provides valuable neurosurgical guidance during MVD for HFS. This simple modification of intra-operative monitoring may improve prediction of satisfactory MVD and HFS resolution.

Characterization of GSK'963: a structurally distinct, potent and selective inhibitor of RIP1 kinase.

Necroptosis and signaling regulated by RIP1 kinase activity is emerging as a key driver of inflammation in a variety of disease settings. A significant amount has been learned about how RIP1 regulates necrotic cell death through the use of the RIP1 kinase inhibitor Necrostatin-1 (Nec-1). Nec-1 has been a transformational tool for exploring the function of RIP1 kinase activity; however, its utility is somewhat limited by moderate potency, off-target activity against indoleamine-2,3-dioxygenase (IDO), and poor pharmacokinetic properties. These limitations of Nec-1 have driven an effort to identify next-generation tools to study RIP1 function, and have led to the identification of 7-Cl-O-Nec-1 (Nec-1s), which has improved pharmacokinetic properties and lacks IDO inhibitory activity. Here we describe the characterization of GSK'963, a chiral small-molecule inhibitor of RIP1 kinase that is chemically distinct from both Nec-1 and Nec-1s. GSK'963 is significantly more potent than Nec-1 in both biochemical and cellular assays, inhibiting RIP1-dependent cell death with an IC50 of between 1 and 4 nM in human and murine cells. GSK'963 is >10 000-fold selective for RIP1 over 339 other kinases, lacks measurable activity against IDO and has an inactive enantiomer, GSK'962, which can be used to confirm on-target effects. The increased in vitro potency of GSK'963 also translates in vivo, where GSK'963 provides much greater protection from hypothermia at matched doses to Nec-1, in a model of TNF-induced sterile shock. Together, we believe GSK'963 represents a next-generation tool for examining the function of RIP1 in vitro and in vivo, and should help to clarify our current understanding of the role of RIP1 in contributing to disease pathogenesis.

Quality assessment of the blue mussel (Mytilus edulis): comparison between commercial and wild types.

This study compared species identity, microplastics, chemical and microbial contamination between consumption mussels and wild type mussels, collected at Belgian department stores and Belgian groynes and quaysides, respectively. Species identification based on genetic analysis showed a high number of Mytilus (M.) edulis compared to M. galloprovincialis and M. edulis/galloprovincialis hybrid mussels. The number of total microplastics varied from 2.6 to 5.1 fibres/10 g of mussel. A higher prevalence of orange fibres at quaysides is related to fisheries activities. Chemical contamination of polycyclic aromatic hydrocarbons and polychlorobiphenyls could be related to industrial activities and water turbidity, with maximum concentrations at the quayside of port Zeebrugge. The inverse was noted for Escherichia coli contamination, which was relatively low at Zeebrugge quayside with a total count of 3.9 × 10(2)CFU/100 g tissue, due to limited agricultural effluents. Results of this complementary analysis stress the importance of integrated monitoring and quality assessment.

Landscape models for nuclear genetic diversity and genetic structure in white-footed mice (Peromyscus leucopus).

Dramatic changes in the North American landscape over the last 12 000 years have shaped the genomes of the small mammals, such as the white-footed mouse (Peromyscus leucopus), which currently inhabit the region. However, very recent interactions of populations with each other and the environment are expected to leave the most pronounced signature on rapidly evolving nuclear microsatellite loci. We analyzed landscape characteristics and microsatellite markers of P. leucopus populations along a transect from southern Ohio to northern Michigan, in order to evaluate hypotheses about the spatial distribution of genetic heterogeneity. Genetic diversity increased to the north and was best approximated by a single-variable model based on habitat availability within a 0.5-km radius of trapping sites. Interpopulation differentiation measured by clustering analysis was highly variable and not significantly related to latitude or habitat availability. Interpopulation differentiation measured as FST values and chord distance was correlated with the proportion of habitat intervening, but was best explained by agricultural distance and by latitude. The observed gradients in diversity and interpopulation differentiation were consistent with recent habitat availability being the major constraint on effective population size in this system, and contradicted the predictions of both the postglacial expansion and core-periphery hypotheses.

Issue brief: strengthening national health systems' capacity to respond to future global pandemics

Effective pandemic governance is more important now than ever as pandemic risk factors like urbanization, the hypermobility of persons, trans-border trade, rapid population growth and changes to the environment and food systems all increase in tandem with the demands of globalization.(1) These transformative global shifts have fundamentally changed the way pathogens are spread around the world.(2) The World Health Organization (WHO) estimates that newly emerging infectious disease outbreaks in one country are now only hours away from affecting many others.(3) Pandemics previously spread over years (e.g., bubonic plague in the 14th century), months (e.g., cholera epidemics in 19th century) or weeks (e.g., Spanish influenza of 1918-1919), but in today's globalized world, Severe Acute Respiratory Syndrome (SARS) took only 17 hours to spread half-way around the world from China to Canada. Future disease outbreaks are expected to take similarly short periods before they affect multiple countries across geographically distinct regions.(3) The current outbreak of H7N9 bird influenza in China (which spreads more easily from infected fowl to humans than the H5N1 strain did in 2003, according to Dr. Keiji Fukuda, WHO's top influenza expert) is a stark reminder that the threat of a pandemic exists as an imminent threat to human health and international security.(4) Of notable concern is the fact that more than 30 unexpected outbreaks of previously unknown pathogens and re-emerging diseases were observed in the past two decades alone.(2) Although the great majority of new and re-emerging diseases have not caused pandemics, national health systems that can respond adequately to pandemic threats are fundamental to controlling pandemic-prone local disease outbreaks within a country or a region

The immunologic self.

Immunology has been referred to as the science of self/non-self discrimination. Who or what is the "I" of which we often speak? It has been identified with body, brain, soul, and memories. There has been a diversity of ways to characterize the self, including denying its importance and existence, and to date no satisfactory conceptualization has been achieved. This article addresses the concept of self from an immunological perspective, a perspective that offers insights into the philosophic issues associated with the concept of self and personal identity. The article proposes that the immunological and the psychological are two aspects of one and the same self, offers criteria for an adequate conceptualization of the self, and discusses the philosophical and psychological implications of the immunological views of self. It concludes that we must move away from a simplistic, exclusively inward or mentalistic conception of the self.

Loss of caveolin-1 from bronchial epithelial cells and monocytes in human subjects with asthma.

BACKGROUND: Caveolin-1 has emerged as a critical regulator of signaling pathways involved in lung fibrosis and inflammation. METHODS: Therefore, we investigated whether caveolin-1 is deficient in asthmatic patients and in a murine model of asthma. RESULTS: Immunohistochemical analyses of endobronchial biopsies showed a remarkable loss of caveolin-1 in the lungs of asthmatic patients compared with controls. This loss was most evident in bronchial epithelial cells and associated with an increase in the expression of extracellular matrix proteins: collagen I, tenascin, and periostin. Cultured primary bronchial epithelial cells of asthmatics had lower caveolin-1 expression compared with control cells. In addition, caveolin-1 expression was significantly decreased in peripheral blood monocytes from asthma patients. The loss of caveolin-1 was also observed in a mouse model for asthma (mice sensitized and challenged with aspergillus fumigatus). CONCLUSIONS: To our knowledge, this is the first demonstration that the regulatory protein caveolin-1 is reduced in patients with asthma.

Focusing through dynamic scattering media.

We demonstrate steady-state focusing of coherent light through dynamic scattering media. The phase of an incident beam is controlled both spatially and temporally using a reflective, 1020-segment MEMS spatial light modulator, using a coordinate descent optimization technique. We achieve focal intensity enhancement of between 5 and 400 for dynamic media with speckle decorrelation time constants ranging from 0.4 seconds to 20 seconds. We show that this optimization approach combined with a fast spatial light modulator enables focusing through dynamic media. The capacity to enhance focal intensity despite transmission through dynamic scattering media could enable advancement in biological microscopy and imaging through turbid environments.