Near infra-red photoimmunotherapy with anti-CEA-IR700 results in extensive tumor lysis and a significant decrease in tumor burden in orthotopic mouse models of pancreatic cancer.

Photoimmunotherapy (PIT) of cancer utilizes tumor-specific monoclonal antibodies conjugated to a photosensitizer phthalocyanine dye IR700 which becomes cytotoxic upon irradiation with near infrared light. In this study, we aimed to evaluate the efficacy of PIT on human pancreatic cancer cells in vitro and in vivo in an orthotopic nude mouse model. The binding capacity of anti-CEA antibody to BxPC-3 human pancreatic cancer cells was determined by FACS analysis. An in vitro cytotoxicity assay was used to determine cell death following treatment with PIT. For in vivo determination of PIT efficacy, nude mice were orthotopically implanted with BxPC-3 pancreatic tumors expressing green fluorescent protein (GFP). After tumor engraftment, the mice were divided into two groups: (1) treatment with anti-CEA-IR700 + 690 nm laser and (2) treatment with 690 nm laser only. Anti-CEA-IR700 (100 μg) was administered to group (1) via tail vein injection 24 hours prior to therapy. Tumors were then surgically exposed and treated with phototherapy at an intensity of 150 mW/cm2 for 30 minutes. Whole body imaging was done subsequently for 5 weeks using an OV-100 small animal imaging system. Anti-CEA-IR700 antibody bound to the BxPC3 cells to a high degree as shown by FACS analysis. Anti-CEA-IR700 caused extensive cancer cell killing after light activation compared to control cells in cytotoxicity assays. In the orthotopic models of pancreatic cancer, the anti-CEA-IR700 group had significantly smaller tumors than the control after 5 weeks (p<0.001). There was no significant difference in the body weights of mice in the anti-CEA-IR700 and control groups indicating that PIT was well tolerated by the mice

Clinical utility of a pediatric hand exoskeleton: identifying users, practicability, and acceptance, and recommendations for design improvement

BACKGROUND Children and adolescents with upper limb impairments can experience limited bimanual performance reducing daily-life independence. We have developed a fully wearable pediatric hand exoskeleton (PEXO) to train or compensate for impaired hand function. In this study, we investigated its appropriateness, practicability, and acceptability. METHODS Children and adolescents aged 6-18 years with functional limitations in at least one hand due to a neurological cause were selected for this cross-sectional evaluation. We characterized participants by various clinical tests and quantified bimanual performance with the Assisting Hand Assessment (AHA). We identified children whose AHA scaled score increased by ≥ 7 points when using the hand exoskeleton and determined clinical predictors to investigate appropriateness. The time needed to don each component and the number of technical issues were recorded to evaluate practicability. For acceptability, the experiences of the patients and the therapist with PEXO were evaluated. We further noted any adverse events. RESULTS Eleven children (median age 11.4 years) agreed to participate, but data was available for nine participants. The median AHA scaled score was higher with PEXO (68; IQR: 59.5-83) than without (55; IQR: 37.5-80.5; p = 0.035). The Box and Block test, the Selective Control of the Upper Extremity Scale, and finger extensor muscle strength could differentiate well between those participants who improved in AHA scaled scores by ≥ 7 points and those who did not (sensitivity and specificity varied between 0.75 and 1.00). The median times needed to don the back module, the glove, and the hand module were 62, 150, and 160 s, respectively, but all participants needed assistance. The most critical failures were the robustness of the transmission system, the electronics, and the attachment system. Acceptance was generally high, particularly in participants who improved bimanual performance with PEXO. Five participants experienced some pressure points. No adverse events occurred. CONCLUSIONS PEXO is a safe exoskeleton that can improve bimanual hand performance in young patients with minimal hand function. PEXO receives high acceptance. We formulated recommendations to improve technical issues and the donning before such exoskeletons can be used under daily-life conditions for therapy or as an assistive device. Trial registration Not appropriate

Methyl mercury dynamics in a tidal wetland quantified using in situ optical measurements

Author Posting. © American Society of Limnology and Oceanography, 2011. This article is posted here by permission of American Society of Limnology and Oceanography for personal use, not for redistribution. The definitive version was published in Limnology and Oceanography 56 (2011): 1355-1371, doi:10.4319/lo.2011.56.4.1355.We assessed monomethylmercury (MeHg) dynamics in a tidal wetland over three seasons using a novel method that employs a combination of in situ optical measurements as concentration proxies. MeHg concentrations measured over a single spring tide were extended to a concentration time series using in situ optical measurements. Tidal fluxes were calculated using modeled concentrations and bi-directional velocities obtained acoustically. The magnitude of the flux was the result of complex interactions of tides, geomorphic features, particle sorption, and random episodic events such as wind storms and precipitation. Correlation of dissolved organic matter quality measurements with timing of MeHg release suggests that MeHg is produced in areas of fluctuating redox and not limited by buildup of sulfide. The wetland was a net source of MeHg to the estuary in all seasons, with particulate flux being much higher than dissolved flux, even though dissolved concentrations were commonly higher. Estimated total MeHg yields out of the wetland were approximately 2.5 µg m−2 yr−1—4–40 times previously published yields—representing a potential loading to the estuary of 80 g yr−1, equivalent to 3% of the river loading. Thus, export from tidal wetlands should be included in mass balance estimates for MeHg loading to estuaries. Also, adequate estimation of loads and the interactions between physical and biogeochemical processes in tidal wetlands might not be possible without long-term, high-frequency in situ measurements.This work was supported by funding from the California Bay Delta Authority Ecosystem Restoration and Drinking Water Programs (grant ERP-00-G01) and matching funds from the U.S. Geological Survey Cooperative Research Program

Mercury Dynamics in a San Francisco Estuary Tidal Wetland: Assessing Dynamics Using In Situ Measurements

We used high-resolution in situ measurements of turbidity and fluorescent dissolved organic matter (FDOM) to quantitatively estimate the tidally driven exchange of mercury (Hg) between the waters of the San Francisco estuary and Browns Island, a tidal wetland. Turbidity and FDOM-representative of particle-associated and filter-passing Hg, respectively-together predicted 94 % of the observed variability in measured total mercury concentration in unfiltered water samples (UTHg) collected during a single tidal cycle in spring, fall, and winter, 2005-2006. Continuous in situ turbidity and FDOM data spanning at least a full spring-neap period were used to generate UTHg concentration time series using this relationship, and then combined with water discharge measurements to calculate Hg fluxes in each season. Wetlands are generally considered to be sinks for sediment and associated mercury. However, during the three periods of monitoring, Browns Island wetland did not appreciably accumulate Hg. Instead, gradual tidally driven export of UTHg from the wetland offset the large episodic on-island fluxes associated with high wind events. Exports were highest during large spring tides, when ebbing waters relatively enriched in FDOM, dissolved organic carbon (DOC), and filter-passing mercury drained from the marsh into the open waters of the estuary. On-island flux of UTHg, which was largely particle-associated, was highest during strong winds coincident with flood tides. Our results demonstrate that processes driving UTHg fluxes in tidal wetlands encompass both the dissolved and particulate phases and multiple timescales, necessitating longer term monitoring to adequately quantify fluxes

TOWARD GLOBAL DROUGHT EARLY WARNING CAPABILITY: Expanding International Cooperation for the Development of a Framework for Monitoring and Forecasting

The need for a global drought early warning framework. Drought has had a significant impact on civilization throughout history in terms of reductions in agricultural productivity, potable water supply, and economic activity, and in extreme cases this has led to famine. Every continent has semiarid areas, which are especially vulnerable to drought. The Intergovernmental Panel on Climate Change has noted that average annual river runoff and water availability are projected to decrease by 10%–13% over some dry and semiarid regions in mid and low latitudes, increasing the frequency, intensity, and duration of drought, along with its associated impacts. The sheer magnitude of the problem demands efforts to reduce vulnerability to drought by moving away from the reactive, crisis management approach of the past toward a more proactive, risk management approach that is centered on reducing vulnerability to drought as much as possible while providing early warning of evolving drought conditions and possible impacts. Many countries, unfortunately, do not have adequate resources to provide early warning, but require outside support to provide the necessary early warning information for risk management. Furthermore, in an interconnected world, the need for information on a global scale is crucial for understanding the prospect of declines in agricultural productivity and associated impacts on food prices, food security, and potential for civil conflict

Toward Global Drought Early Warning Capability - Expanding International Cooperation for the Development of a Framework for Monitoring and Forecasting

Drought has had a significant impact on civilization throughout history in terms of reductions in agricultural productivity, potable water supply, and economic activity, and in extreme cases this has led to famine. Every continent has semiarid areas, which are especially vulnerable to drought. The Intergovernmental Panel on Climate Change has noted that average annual river runoff and water availability are projected to decrease by 10 percent-13 percent over some dry and semiarid regions in mid and low latitudes, increasing the frequency, intensity, and duration of drought, along with its associated impacts. The sheer magnitude of the problem demands efforts to reduce vulnerability to drought by moving away from the reactive, crisis management approach of the past toward a more proactive, risk management approach that is centered on reducing vulnerability to drought as much as possible while providing early warning of evolving drought conditions and possible impacts. Many countries, unfortunately, do not have adequate resources to provide early warning, but require outside support to provide the necessary early warning information for risk management. Furthermore, in an interconnected world, the need for information on a global scale is crucial for understanding the prospect of declines in agricultural productivity and associated impacts on food prices, food security, and potential for civil conflict. This paper highlights the recent progress made toward a Global Drought Early Warning Monitoring Framework (GDEWF), an underlying partnership and framework, along with its Global Drought Early Warning System (GDEWS), which is its interoperable information system, and the organizations that have begun working together to make it a reality. The GDEWF aims to improve existing regional and national drought monitoring and forecasting capabilities by adding a global component, facilitating continental monitoring and forecasting (where lacking), and improving these tools at various scales, thereby increasing the capacity of national and regional institutions that lack drought early warning systems or complementing existing ones. A further goal is to improve coordination of information delivery for drought-related activities and relief efforts across the world. This is especially relevant for regions and nations with low capacity for drought early warning. To do this requires a global partnership that leverages the resources necessary and develops capabilities at the global level, such as global drought forecasting combined with early warning tools, global real-time monitoring, and harmonized methods to identify critical areas vulnerable to drought. Although the path to a fully functional GDEWS is challenging, multiple partners and organizations within the drought, forecasting, agricultural, and water-cycle communities are committed to working toward its success

Mercury dynamics in a San Francisco estuary tidal wetland : assessing dynamics using in situ measurements

© The Author(s), 2012. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Estuaries and Coasts 35 (2012): 1036-1048, doi:10.1007/s12237-012-9501-3.We used high-resolution in situ measurements of turbidity and fluorescent dissolved organic matter (FDOM) to quantitatively estimate the tidally driven exchange of mercury (Hg) between the waters of the San Francisco estuary and Browns Island, a tidal wetland. Turbidity and FDOM—representative of particle-associated and filter-passing Hg, respectively—together predicted 94 % of the observed variability in measured total mercury concentration in unfiltered water samples (UTHg) collected during a single tidal cycle in spring, fall, and winter, 2005–2006. Continuous in situ turbidity and FDOM data spanning at least a full spring-neap period were used to generate UTHg concentration time series using this relationship, and then combined with water discharge measurements to calculate Hg fluxes in each season. Wetlands are generally considered to be sinks for sediment and associated mercury. However, during the three periods of monitoring, Browns Island wetland did not appreciably accumulate Hg. Instead, gradual tidally driven export of UTHg from the wetland offset the large episodic on-island fluxes associated with high wind events. Exports were highest during large spring tides, when ebbing waters relatively enriched in FDOM, dissolved organic carbon (DOC), and filter-passing mercury drained from the marsh into the open waters of the estuary. On-island flux of UTHg, which was largely particle-associated, was highest during strong winds coincident with flood tides. Our results demonstrate that processes driving UTHg fluxes in tidal wetlands encompass both the dissolved and particulate phases and multiple timescales, necessitating longer term monitoring to adequately quantify fluxes.This work was supported by funding from the California Bay Delta Authority Ecosystem Restoration and Drinking Water Programs (grant ERP-00- G01) and matching funds from the United States Geological Survey Cooperative Research Program

The gender specific frequency of risk factor and CHD diagnoses prior to incident MI: A community study

BACKGROUND: CHD is a chronic disease often present years prior to incident AMI. Earlier recognition of CHD may be associated with higher levels of recognition and treatment of CHD risk factors that may delay incident AMI. To assess timing of CHD and CHD risk factor diagnoses prior to incident AMI. METHODS: This is a 10-year population based medical record review study that included all medical care providers in Olmsted County, Minnesota for all women and a sample of men residing in Olmsted County, MN with confirmed incident AMI between 1995 and 2000. RESULTS: All medical care for the 10 years prior to incident AMI was reviewed for 150 women and 148 men (38% sample) in Olmsted County, MN. On average, women were older than men at the time of incident AMI (74.7 versus 65.9 years, p < 0.0001). 30.4% of the men and 52.0% of the women received diagnoses of CHD prior to incident AMI (p = 0.0002). Unrecognized and untreated CHD risk factors were present in both men (45% of men 5 years prior to AMI) and women (22% of women 5 years prior to first AMI), more common in men and those without a diagnosis of CHD prior to incident AMI (p < 0.0001). CONCLUSION: A CHD diagnosis prior to incident AMI is associated with higher rates of recognition and treatment of CHD risk factors suggesting that diagnosing CHD prior to AMI enhances opportunities to lower the risk of future CHD events

Functional Fluorescent Ca(2+) Indicator Proteins in Transgenic Mice under TET Control

Genetically encoded fluorescent calcium indicator proteins (FCIPs) are promising tools to study calcium dynamics in many activity-dependent molecular and cellular processes. Great hopes—for the measurement of population activity, in particular—have therefore been placed on calcium indicators derived from the green fluorescent protein and their expression in (selected) neuronal populations. Calcium transients can rise within milliseconds, making them suitable as reporters of fast neuronal activity. We here report the production of stable transgenic mouse lines with two different functional calcium indicators, inverse pericam and camgaroo-2, under the control of the tetracycline-inducible promoter. Using a variety of in vitro and in vivo assays, we find that stimuli known to increase intracellular calcium concentration (somatically triggered action potentials (APs) and synaptic and sensory stimulation) can cause substantial and rapid changes in FCIP fluorescence of inverse pericam and camgaroo-2