Evaluation Research and the Psychiatric Hospital: Blending Management and Inquiry in Clinical Sociology

This paper discusses the multiple roles sociologists play in conducting evaluation research in a large state psychiatric hospital. The key to understanding this form of clinical sociology is its blending of management and inquiry in a unique organizational context. The authors, sociologists who have both served as directors of the Buffalo Psychiatric Center\u27s program evaluation unit since its founding in 1979, present examples of the unit\u27s work, discussing the role sociologists play in the collection, analysis and reporting of data used by hospital administrators for strategic planning, continuous quality improvement programs, and the monitoring of patterns and trends for census management, workload and staffing projections. The conduct of program evaluation and applied research in mental health care has been influenced by public policy, budgetary constraints, changes in national standards used in accrediting psychiatric hospitals, and the introduction of personal computers into the workplace. Several suggestions for improving the training of sociologists interested in this form of clinical practice are offered

RidA proteins prevent metabolic damage inflicted by PLP-dependent dehydratases in all domains of life

ABSTRACT Pyridoxal 5′-phosphate (PLP) is a coenzyme synthesized by all forms of life. Relevant to the work reported here is the mechanism of the PLP-dependent threonine/serine dehydratases, which generate reactive enamine/imine intermediates that are converted to keto acids by members of the RidA family of enzymes. The RidA protein of Salmonella enterica serovar Typhimurium LT2 is the founding member of this broadly conserved family of proteins (formerly known as YjgF/YER057c/UK114). RidA proteins were recently shown to be enamine deaminases. Here we demonstrate the damaging potential of enamines in the absence of RidA proteins. Notably, S. enterica strains lacking RidA have decreased activity of the PLP-dependent transaminase B enzyme IlvE, an enzyme involved in branched-chain amino acid biosynthesis. We reconstituted the threonine/serine dehydratase (IlvA)-dependent inhibition of IlvE in vitro, show that the in vitro system reflects the mechanism of RidA function in vivo, and show that IlvE inhibition is prevented by RidA proteins from all domains of life. We conclude that 2-aminoacrylate (2AA) inhibition represents a new type of metabolic damage, and this finding provides an important physiological context for the role of the ubiquitous RidA family of enamine deaminases in preventing damage by 2AA. IMPORTANCE External stresses that disrupt metabolic components can perturb cellular functions and affect growth. A similar consequence is expected if endogenously generated metabolites are reactive and persist in the cellular environment. Here we show that the metabolic intermediate 2-aminoacrylate (2AA) causes significant cellular damage if allowed to accumulate aberrantly. Furthermore, we show that the widely conserved protein RidA prevents this accumulation by facilitating conversion of 2AA to a stable metabolite. This work demonstrates that the reactive metabolite 2AA, previously considered innocuous in the cell due to a short half-life in aqueous solution, can survive in the cellular environment long enough to cause damage. This work provides insights into the roles and persistence of reactive metabolites in vivo and shows that the RidA family of proteins is able to prevent damage caused by a reactive intermediate that is created as a consequence of PLP-dependent chemistry

High resolution mapping of Puget Sound shorelines

In an effort to collect high-resolution baseline coastal topographic data of beaches and bluffs around the Puget Sound and Strait of Juan de Fuca, the Washington State Department of Ecology Coastal Monitoring & Analysis Program (CMAP) conducted a series of boat-based lidar surveys in October 2013, May through September 2015, and May 2016 at a total of 16 sites spanning 220 km of shoreline and over two dozen drift cells. The drift cells were selected based on a rigorous and systematic geospatial analysis of bluff-backed beaches for their potential for significant bluff sediment supply to intact shorelines identified as having a relative abundance of habitat for forage fish, eelgrass, herring, shellfish, and geoduck, as well as having previous investments in beach restoration projects, and potential for future shoreline armoring and habitat loss based on population growth scenarios. As such, the surveyed drift cells are top candidates for implementing drift cell-scale protection and restoration strategies. The boat-based lidar and GPS topography data were used to produce 0.5-m digital elevation models (DEMs) for the beaches and bluffs at each of the survey sites. These DEMs provide the opportunity to inventory and characterize the shoreline landscape that affects nearshore ecosystem services such as feeder bluff activity, beach slope and width, and the position, length, and elevation of armoring relative to the backshore. Boat-based lidar provides an advantageous point of view of the bluff face, resulting in high resolution data which is needed to gain insight into bluff failure and erosion mechanisms and corresponding sediment transport processes. In addition, it successfully collects data under overhanging vegetation and overwater structures. Repeat surveys in the future would enable change analyses for quantifying bluff sediment supply, changes in marine riparian vegetation, and a better understanding of the linkages between physical and ecological processes

Evaluating methods to obtain high resolution nearshore bathymetry and coastal topography for Puget Sound

The Washington State Department of Ecology Coastal Monitoring & Analysis Program performed a coastal topographic and bathymetric survey of Port Gamble Bay between March 9 and March 28, 2014. Boat-based topographic lidar was collected along the shoreline of the bay and multibeam bathymetric sonar was collected throughout the bay to obtain a seamless topographic-bathymetric surface with complete coverage of Port Gamble Bay. The survey was performed with a R2Sonic 2022 multibeam echosounder, an Optech ILRIS-HD-ER mobile laser scanner, and an Applanix POS MV 320 v5 receiving real-time kinematic positioning corrections. The Joint Airborne Lidar Bathymetry Technical Center of Expertise (JALBTCX) performed a topographic and bathymetric lidar survey of Port Gamble Bay on September 4, 2014. The Coastal Zone Mapping and Imaging Lidar (CZMIL) system was used to obtain seamless coastal topographic-bathymetric coastal intertidal and nearshore coverage of Port Gamble Bay. The bathymetric depth coverage is limited to laser extinction, which is determined by water clarity. The availability of these two datasets provides the unique opportunity to compare data between high-resolution boat-based lidar and multibeam systems and the state-of-the-art airborne topo-bathy lidar system and also assess detection and resolution of specific features throughout a range of water depths across the nearshore important to habitat and restoration efforts. This effort provides a detailed comparison of coverage and resolution of nearshore features and will help clarify differences between these capabilities to aid in planning complementary efforts in coastal zone mapping and monitoring

Could blackbird mortality from avicide DRC-1339 contribute to avian botulism outbreaks in North Dakota?

Blackbird (family Icteridae) depredation on sunflower (Helianthus annuus) crops in the prairie states of the United States has motivated the proposed use of an avicide, DRC-1339 (3-chloro-4-methylaniline), to decrease their numbers. The resulting mortality of blackbirds at wetland roosts could increase the potential of avian botulism occurring in affected marshes. To assess this possibility, we seeded (artificially placed) blackbird carcasses in selected wetlands in Stutsman County, North Dakota, during August–September 2000 and July–September 2001 to evaluate their rate of decomposition and role in initiating avian botulism outbreaks. We monitored carcasses to determine their persistence, the frequency and amount of maggots produced, and the presence of type C. botulinum toxin. In 10 of our 12 study wetlands, blackbird carcasses were not rapidly removed by scavengers, thus providing substrate for maggot growth and potential production of Clostridium botulinum toxin. Decomposition of carcasses occurred rapidly, and maggot production averaged 4–5 g per carcass within 9 days. We were unable to detect C. botulinum type C toxin in any of the 377 blackbird carcasses or the 112 samples of maggots we collected in 2000 or 2001. None of the 25 blackbird carcasses we tested contained botulinum spores, the most probable explanation for the absence of botulinum toxin production. Our results indicate that the likelihood of DRC-1339-poisoned blackbirds causing botulism outbreaks would be minimal in North Dakota wetlands during late summer and early autumn

Mode of inhibition of HIV-1 Integrase by a C-terminal domain-specific monoclonal antibody*

BACKGROUND: To further our understanding of the structure and function of HIV-1 integrase (IN) we developed and characterized a library of monoclonal antibodies (mAbs) directed against this protein. One of these antibodies, mAb33, which is specific for the C-terminal domain, was found to inhibit HIV-1 IN processing activity in vitro; a corresponding Fv fragment was able to inhibit HIV-1 integration in vivo. Our subsequent studies, using heteronuclear nuclear magnetic resonance spectroscopy, identified six solvent accessible residues on the surface of the C-terminal domain that were immobilized upon binding of the antibody, which were proposed to comprise the epitope. Here we test this hypothesis by measuring the affinity of mAb33 to HIV-1 proteins that contain Ala substitutions in each of these positions. To gain additional insight into the mode of inhibition we also measured the DNA binding capacity and enzymatic activities of the Ala substituted proteins. RESULTS: We found that Ala substitution of any one of five of the putative epitope residues, F223, R224, Y226, I267, and I268, caused a decrease in the affinity of the mAb33 for HIV-1 IN, confirming the prediction from NMR data. Although IN derivatives with Ala substitutions in or near the mAb33 epitope exhibited decreased enzymatic activity, none of the epitope substitutions compromised DNA binding to full length HIV-1 IN, as measured by surface plasmon resonance spectroscopy. Two of these derivatives, IN (I276A) and IN (I267A/I268A), exhibited both increased DNA binding affinity and uncharacteristic dissociation kinetics; these proteins also exhibited non-specific nuclease activity. Results from these investigations are discussed in the context of current models for how the C-terminal domain interacts with substrate DNA. CONCLUSION: It is unlikely that inhibition of HIV-1 IN activity by mAb33 is caused by direct interaction with residues that are essential for substrate binding. Rather our findings are most consistent with a model whereby mAb33 binding distorts or constrains the structure of the C-terminal domain and/or blocks substrate binding indirectly. The DNA binding properties and non-specific nuclease activity of the I267A derivatives suggest that the C-terminal domain of IN normally plays an important role in aligning the viral DNA end for proper processing

Genetics of Late-Onset Alzheimer's Disease: Update from the Alzgene Database and Analysis of Shared Pathways

The genetics of late-onset Alzheimer's disease (LOAD) has taken impressive steps forwards in the last few years. To date, more than six-hundred genes have been linked to the disorder. However, only a minority of them are supported by a sufficient level of evidence. This review focused on such genes and analyzed shared biological pathways. Genetic markers were selected from a web-based collection (Alzgene). For each SNP in the database, it was possible to perform a meta-analysis. The quality of studies was assessed using criteria such as size of research samples, heterogeneity across studies, and protection from publication bias. This produced a list of 15 top-rated genes: APOE, CLU, PICALM, EXOC3L2, BIN1, CR1, SORL1, TNK1, IL8, LDLR, CST3, CHRNB2, SORCS1, TNF, and CCR2. A systematic analysis of gene ontology terms associated with each marker showed that most genes were implicated in cholesterol metabolism, intracellular transport of beta-amyloid precursor, and autophagy of damaged organelles. Moreover, the impact of these genes on complement cascade and cytokine production highlights the role of inflammatory response in AD pathogenesis. Gene-gene and gene-environment interactions are prominent issues in AD genetics, but they are not specifically featured in the Alzgene database

The Epithelial Cell-Derived Atopic Dermatitis Cytokine TSLP Activates Neurons to Induce Itch

SummaryAtopic dermatitis (AD) is a chronic itch and inflammatory disorder of the skin that affects one in ten people. Patients suffering from severe AD eventually progress to develop asthma and allergic rhinitis, in a process known as the “atopic march.” Signaling between epithelial cells and innate immune cells via the cytokine thymic stromal lymphopoietin (TSLP) is thought to drive AD and the atopic march. Here, we report that epithelial cells directly communicate to cutaneous sensory neurons via TSLP to promote itch. We identify the ORAI1/NFAT calcium signaling pathway as an essential regulator of TSLP release from keratinocytes, the primary epithelial cells of the skin. TSLP then acts directly on a subset of TRPA1-positive sensory neurons to trigger robust itch behaviors. Our results support a model whereby calcium-dependent TSLP release by keratinocytes activates both primary afferent neurons and immune cells to promote inflammatory responses in the skin and airways

Plasmonic field confinement for separate absorption-multiplication in InGaAs nanopillar avalanche photodiodes

Avalanche photodiodes (APDs) are essential components in quantum key distribution systems and active imaging systems requiring both ultrafast response time to measure photon time of flight and high gain to detect low photon flux. The internal gain of an APD can improve system signal-to-noise ratio (SNR). Excess noise is typically kept low through the selection of material with intrinsically low excess noise, using separate-absorption-multiplication (SAM) heterostructures, or taking advantage of the dead-space effect using thin multiplication regions. In this work we demonstrate the first measurement of excess noise and gain-bandwidth product in III–V nanopillars exhibiting substantially lower excess noise factors compared to bulk and gain-bandwidth products greater than 200 GHz. The nanopillar optical antenna avalanche detector (NOAAD) architecture is utilized for spatially separating the absorption region from the avalanche region via the NOA resulting in single carrier injection without the use of a traditional SAM heterostructure

Prevalence of GB virus type C in urban Americans infected with human immunodeficiency virus type 1

GBV-C virus infection has been linked to improved clinical outcome in HIV-1 co-infected individuals. The epidemiology of GBV-C has, thus far, been limited to the gay male, HIV(+ )population. Here we describe the prevalence of antibodies against GBV-C envelope glycoprotein E2 and GBV-C viremia in an HIV(+ )inner city population. This study group is predominantly African-American; 41% of the participants are women. The major risk factor for HIV infection is intravenous drug use. Overall, 56% of the study population had evidence of current or past infection with GBV-C. GBV-C exposure was not associated with hepatitis C virus infection. The group of participants, who had GBV-C viremia and anti-E2 antibodies, had high percentage of patients with an undetectable HIV-1 viral load. These data provide increased insight into the prevalence of GBV-C co-infection in the HIV epidemic in this understudied population