Development and validation of an open-source four-pole electrical conductivity, temperature, depth sensor for in situ water quality monitoring in an estuary.

Most recent implementations of low-cost electrical conductivity (EC) sensors intended for water quality measurements are based on simple two-pole designs. However, in marine settings, EC often exceeds the range where two-pole sensors provide reliable results. We have developed a simple four-pole EC sensor that relies exclusively on analog-to-digital measurements made using readily available circuit boards (pyboard v.1.1 or Raspberry Pi Pico 2040) programmed using MicroPython. Other than resistors and graphite or wire electrodes, no other electronic components are required for the EC sensor. When combined with a pressure/temperature sensor (MS5803-05), an optional NTC thermistor, batteries, and a waterproof housing constructed using a PVC pipe and a 3-D-printed cap, the device becomes a working conductivity-temperature-depth sensor capable of extended field deployments. Construction is sufficiently simple that undergraduate science students can construct one during three 3-h lab periods. Lab calibrations performed on several prototypes at ECs between 0.18 and 45 mS/cm show that confidence limits as good as about ±3% of EC are possible. Re-calibration of several prototypes 1 year after initial calibration shows that long-term calibration drift is modest. Data collected by the prototypes over several tidal cycles in the Duwamish River, Washington, USA, are in agreement with data from a co-located commercial YSI-EX03 conductivity probe. When distributed across a constructed off-channel wetland in the Duwamish system, the sensors documented large amounts of spatial and temporal variability in EC, highlighting the importance of such wetlands for providing unique temperature/salinity environments potentially valuable for outmigrating juvenile salmon.

Critical Uncertainties and Gaps in the Environmental- and Social-Impact Assessment of the Proposed Interoceanic Canal through Nicaragua.

The proposed interoceanic canal will connect the Caribbean Sea with the Pacific Ocean, traversing Lake Nicaragua, the major freshwater reservoir in Central America. If completed, the canal would be the largest infrastructure-related excavation project on Earth. In November 2015, the Nicaraguan government approved an environmental and social impact assessment (ESIA) for the canal. A group of international experts participated in a workshop organized by the Academy of Sciences of Nicaragua to review this ESIA. The group concluded that the ESIA does not meet international standards; essential information is lacking regarding the potential impacts on the lake, freshwater and marine environments, and biodiversity. The ESIA presents an inadequate assessment of natural hazards and socioeconomic disruptions. The panel recommends that work on the canal project be suspended until an appropriate ESIA is completed. The project should be resumed only if it is demonstrated to be economically feasible, environmentally acceptable, and socially beneficial.

Mesoaxial polydactyly is a major feature in Bardet-Biedl syndrome patients with LZTFL1 (BBS17) mutations.

Ciliopathies are heterogeneous disorders sharing different clinical signs due to a defect at the level of the primary cilia/centrosome complex. Postaxial polydactyly is frequently reported in ciliopathies, especially in Bardet-Biedl syndrome (BBS). Clinical features and genetic results observed in a pair of dizygotic twins with BBS are reported. The following manifestations were present: retinitis pigmentosa, bilateral insertional polydactyly, cognitive impairment and renal dysfunction. X-rays of the hands confirmed the presence of a 4th mesoaxial extra-digit with Y-shaped metacarpal bones. The sequencing of LZTFL1 identified a missense mutation (NM_020347.2: p.Leu87Pro; c.260T>C) and a nonsense mutation (p.Glu260*; c.778G>T), establishing a compound heterozygous status for the twins. A major decrease of LZTFL1 transcript and protein was observed in the patient's fibroblasts. This is the second report of LZTFL1 mutations in BBS patients confirming LZTFL1 as a BBS gene. Interestingly, the only two families reported in literature thus far with LZTFL1 mutations have in common mesoaxial polydactyly, a very uncommon feature for BBS. This special subtype of polydactyly in BBS patients is easily identified on clinical examination and prompts for priority sequencing of LZTFL1 (BBS17).

Large shift in source of fine sediment in the upper Mississippi river.

Although sediment is a natural constituent of rivers, excess loading to rivers and streams is a leading cause of impairment and biodiversity loss. Remedial actions require identification of the sources and mechanisms of sediment supply. This task is complicated by the scale and complexity of large watersheds as well as changes in climate and land use that alter the drivers of sediment supply. Previous studies in Lake Pepin, a natural lake on the Mississippi River, indicate that sediment supply to the lake has increased 10-fold over the past 150 years. Herein we combine geochemical fingerprinting and a suite of geomorphic change detection techniques with a sediment mass balance for a tributary watershed to demonstrate that, although the sediment loading remains very large, the dominant source of sediment has shifted from agricultural soil erosion to accelerated erosion of stream banks and bluffs, driven by increased river discharge. Such hydrologic amplification of natural erosion processes calls for a new approach to watershed sediment modeling that explicitly accounts for channel and floodplain dynamics that amplify or dampen landscape processes. Further, this finding illustrates a new challenge in remediating nonpoint sediment pollution and indicates that management efforts must expand from soil erosion to factors contributing to increased water runoff.

Comparison of visual function and ocular hemodynamics between pre- and post-menopausal women.

PURPOSE: The incidence of eye disease increases with age and can often be linked to worsening cardiovascular function and increasing intraocular pressure. Estrogen is known to have vasodilatory effects in the systemic circulation. Decreased estrogen levels during menopause may therefore complicate or contribute to ocular pathologies as estrogen receptors are found in both retinal and choroidal tissue. The purpose of this investigation was to determine the effects of menopause on visual function and cardiovascular and ocular hemodynamics. METHODS: Twelve premenopausal and 24 postmenopausal women were evaluated at the Indiana University School of Medicine during a single study visit. Vision screening and ocular blood flow evaluations were performed, including blood pressure, heart rate, visual acuity, contrast sensitivity, intraocular pressure, and retinal capillary and retrobulbar blood flow imaging. Vision and ocular hemodynamics were compared using unpaired Student t-tests with p<0.05 regarded as statistically significant. RESULTS: The premenopausal group had significantly lower heart rate (-16.1 b/m, p=0.0001) and systolic blood pressure (-17.7 mmHg, p=0.003) than postmenopausal subjects. Contrast sensitivity was significantly higher (measured in log units) in premenopausal women in both the right (0.25, p=0.039; 0.16, p=0.039) and left (0.45, p=0.001; 0.27, p=0.032) eyes at 9 and 18 cycles per degree, respectively. Premenopausal women also had significantly lower intraocular pressure in both the right (-2.19 mmHg, p=0.024) and left (-1.74 mmHg, p=0.035) eyes. Total ocular perfusion was not significantly different between groups. CONCLUSIONS: This pilot work suggests that postmenopausal women have lower contrast sensitivity detection and elevated intraocular pressures compared to premenopausal women. Premenopausal women have lower cardiovascular risk factors, while total ocular circulation was similar to postmenopausal women.

Kinetics of productive and latent HIV infection in lymphatic tissue and peripheral blood during triple-drug combination therapy with or without additional interleukin-2.

OBJECTIVE: To study decay rates of productively and latently infected cells in peripheral blood and lymph nodes during triple antiretroviral therapy and the possible impact of interleukin-2 (IL-2) on viral kinetics. METHODS: In this non-randomized study, nine antiretroviral-naive HIV-positive patients received either saquinavir hard gel capsules 2400 mg three times daily (group I; four patients) or saquinavir soft gel capsules 1200 mg three times daily and IL-2 (group II), in both cases together with two nucleoside analogues. Plasma viraemia and lymphocyte subsets were analysed. Axillary lymph nodes were excised before and after 12 weeks of therapy. Lymph node sections were examined by in situ hybridization for HIV RNA, and productively infected cells were counted. Infection rates of FACS-sorted CD3, CD4 lymph node and peripheral blood mononuclear cells were determined by nested DNA PCR. RESULTS: Baseline plasma HIV RNA levels ranged from < 25 to > 1 x 10(6) copies/ml and remained undetectable throughout the study in one patient in group I. Plasma viraemia became undetectable after 3 months in four patients (three in group I). Productively infected cells were markedly reduced in the follow-up lymph node specimens. HIV DNA-positive CD4 T cells were reduced in lymphoid tissue and peripheral blood in all six evaluable patients. There were no significant differences between the groups in the clearance rates of plasma virus and of HIV DNA-positive cells. CONCLUSIONS: Combined antiretroviral therapy rapidly suppressed active HIV replication in plasma and lymphoid tissue. Latently infected cells were cleared at a slower rate. Viral clearance did not appear to be markedly affected by additional IL-2 therapy.

In vitro incorporation of synthetic peptides into cells.

This article gives a specific example of how a reversible permeabilization kit can be adapted for use with a specific peptide-based protocol. It was relatively easy to design and run the control experiments to determine the necessary adaptations. The basic procedure given with the TRANS-PORT kit is amenable to modification such that is can be used with numerous other in vitro procedures.

Inhibition of melanoma cell binding to type IV collagen by analogs of cell adhesion regulator.

Integrin-mediated tumor cell adhesion to type IV collagen is believed to play a role in the invasion of basement membrane proteins and the subsequent metastatic process. The cellular protein CAR (cell adhesion regulator) has been proposed to influence integrin-mediated binding to extracellular matrix proteins, including basement membrane (type IV) collagen. Three analogs of the CAR138-142 have been tested for activity. The first contains the 138-142 sequence (CAR138-142, Val-Glu-Ile-Leu-Tyr-NH2), the second contains the 138-142 sequence with a phosphorylated Tyr [pCAR138-142, Val-Glu-Ile-Leu-Tyr(PO3H2)-NH2], and the third contains the reversed 138-142 sequence (rCAR138-142, Tyr-Leu-Ile-Glu-Val-NH2). When added extracellularly, none of the analogs had a significant affect on cell adhesion to type IV collagen. Using a novel reversible cell permeabilization method, we found that intracellular incorporation of both CAR138-142 and pCAR138-142 resulted in inhibition of cell adhesion in a dose-dependent fashion. The IC50 values were approximately 90 and approximately 10 microM for CAR138-142 and pCAR138-142, respectively. Intracellular incorporation of the rCAR138-142 peptide had no affect on cell adhesion. Fluorescence microscopy of a fluorescein-labeled CAR138-142 peptide revealed that the reversible permeabilization procedure resulted in the peptides crossing the cell membrane. Affinity chromatography of melanoma cell lysates with pCAR138-142 or rCAR138-142 attached to a solid support of magnetic beads suggested that one protein was bound uniquely by pCAR138-142. Immunoprecipitation analysis identified vinculin, a protein associated with the actin cytoskeleton, as the protein specifically bound by pCAR138-142. Immunoprecipitation with pp125FAK- or beta 1-integrin-derived mAbs gave negative results. Our study suggests that a possible therapeutic approach for inhibition of melanoma cell adhesion adhesion to extracellular matrix proteins is the use of CAR peptide analogs intracellularly.

"Neutral allografts"--lack of allogeneic stimulation by cultured human cells expressing MHC class I and class II antigens.

Cultured human dermal fibroblasts, smooth muscle cells, epidermal cells and endothelial cells were tested for immunogenicity in an in vitro allostimulation assay. Gamma interferon was used to induce MHC class II expression, since these cells constitutively express class I but not class II antigens. In contrast to human dermal fibroblasts, smooth muscle cells and epidermal cells, endothelial cells, were able to stimulate a significant proliferative response in normal allogeneic lymphocytes. Since ICAM-1 was also expressed on these cells, this inability to initiate allostimulation was probably not due to the absence of adhesion molecules. Addition of exogenous cytokines such as IL-1, IL-2, and TNF did not restore T cell proliferation in the test system. Therefore the inability of dermal fibroblasts, smooth muscle cells, and epidermal cells to initiate significant allostimulation was also not due to lack of cytokine production. It appears that certain cells lack as-yet-undefined costimulatory factors required for their effective recognition as foreign. These results support the notion that cultured human fibroblasts, smooth muscle cells, and epidermal cells could serve as building blocks of engineered "neutral allografts" for use across MHC barriers.

Hemorrhagic complications of thrombolytic therapy.

Thrombolytic therapy salvages ischemic myocardium by rapidly reestablishing coronary artery patency in acute myocardial infarction. One of its major limitations is the complication of hemorrhage. A retrospective study of myocardial infarction patients who received thrombolytic therapy was performed to determine risk factors associated with a hemorrhagic event. Three hundred fifty patients were enrolled, and 20 (5.7%) had a bleeding complication, including four patients (1.1%) who had an intracranial hemorrhage. The factors associated with an increased risk for a significant hemorrhagic event were age (> 65 years) and female gender. Factors associated with an intracranial hemorrhage were age (> 65 years) and a history of hypertension.

Therapeutic effects of local delivery of dexamethasone on experimental brain tumors and peritumoral brain edema.

To determine if dexamethasone administered by osmotic pump directly to brain tumors would control peritumoral edema and at the same time suppress tumor growth and prolong survival, the authors studied experimental brain tumors produced in 102 rabbits by implanting VX2 carcinoma cells. Of these, 58 animals were separated into three treatment groups: Group 1 included 15 untreated rabbits; Group 2 included 18 rabbits treated with systemic dexamethasone (4 mg/kg/day); and Group 3 included 25 rabbits treated with local dexamethasone (0.24 mg/day) delivered by osmotic pump. Systemic or local dexamethasone was administered from Day 3 or Day 7 after tumor implantation, and animals were sacrificed on Day 13. A survival study was performed with 44 rabbits separated into the same treatment groups, beginning drug delivery on Day 7. Brain water content in the white matter of sacrificed animals was measured by the specific gravity method. The length and width of the brain tumors in all animals were measured and the tumor volume estimated. Findings showed that systemic and local dexamethasone administered from Day 3 or Day 7 was associated with a significant (5% level) inhibition of tumor volume as well as a mean reduction of brain edema in most tested sites. Systemic and local dexamethasone therapy also resulted in a significant (5% level) increase in survival time relative to the untreated group. These short-term results suggest that locally delivered dexamethasone may constitute a clinically important therapeutic modality.

Hemispherectomy: a hemidecortication approach and review of 52 cases.

Between 1975 and 1994, 52 hemispherectomies, of which two were anatomical and 50 hemidecortications, were performed at Johns Hopkins Medical Institutions. Eighteen patients were 2 years old or less. There were three perioperative mortalities and one patient died 9 months later from causes not related to surgery. One patient developed hydrocephalus 6 years postsurgery and has been treated effectively. Seizure control and the functional status of each patient were measured as outcome variables. Forty-six (96%) of the surviving patients were seizure free or had reduced seizures as of their last follow-up examination. Twenty-one individuals (44%) were participating in age-appropriate classes or working independently, 18 were classified as semiindependent, and nine children will likely depend on a lifetime of assisted living. The relationships between the outcome variables and the patient's age at surgery, the interval to surgery, and the etiology of the disease were compared. The authors' clinical experiences strongly suggest the importance of a multidisciplinary approach to patient selection and follow-up care. Moreover, anesthetic management of infant surgery is a major component of success.

Perinatal diazepam exposure: behavioral and neurochemical consequences.

In the present study the effects of perinatal diazepam (DZP) exposure on behavior and benzodiazepine binding site characteristics in offspring were investigated. Pregnant F344 rats were treated during the last trimester of gestation with vehicle or diazepam (3 mg/kg, 5 mg/kg, or 10 mg/kg). Lactating dams were similarly treated on postnatal days 1-7. Both prenatal and postnatal exposure to diazepam resulted in significant effects on the acquisition and extinction of active avoidance behavior measured postweaning. The number of trials to extinction of one-way active avoidance behavior was significantly greater in offspring exposed gestationally to 3 mg/kg and 10 mg/kg diazepam and postnatally to 10 mg/kg diazepam. The mean response latencies for all diazepam treated groups were significantly shorter than those of the vehicle treated rats during the first 15 trials under extinction conditions. In contrast, neither gestational nor postnatal diazepam exposure significantly affected either acquisition or retention of a passive avoidance task. In addition, the binding affinity between the benzodiazepine type I selective ligand, CL218,872, and cortical membranes, as well as the degree to which GABA potentiated 3H-flunitrazepam were significantly altered by perinatal diazepam exposure. No treatment altered the approximate number of benzodiazepine binding sites in either the cortex, hippocampus, or cerebellum. The results of this study further support diazepam as a behavioral teratogen and give new evidence for neurochemical effects following gestational as well as postnatal diazepam exposure.

Arteriography of the left internal mammary artery graft utilizing a balloon-tipped floatation catheter: an alternative approach.

In this report, we describe an alternative method to the conventional arteriographic techniques of the left internal mammary artery (LIMA) graft using a balloon-tipped floatation catheter placed within the left subclavian artery. The floatation catheter will serve as both an occluder of the subclavian artery as well as a port for contrast injection. It may be effectively employed in the rare instances where direct cannulation of the LIMA graft is not possible.

Cerebral blood flow in Sjögren's syndrome using 99Tcm-HMPAO brain SPET.

Neuropsychiatric disturbances are frequent in connective tissue diseases. Little is known about the cerebral pathophysiology of Sjögren's syndrome, including cerebral blood flow disturbances. 99Tcm-HMPAO brain SPET was performed in 21 Sjögren's syndrome patients. We also studied 77 patients with systemic lupus erythematosus and 27 healthy individuals. Our results demonstrate the high rate of alterations in cerebral blood flow in Sjögren's syndrome, both psychoneurologically symptomatic and asymptomatic. Focal interhemispherical perfusion deficits were seen in 17 of 21 patients (80.9%) with Sjögren's syndrome: 13/15 symptomatic (86.6%) and 4/6 asymptomatic (66.6%). These changes were mostly localized in the prefrontal and frontal areas, occipital lobes and occipitoparietal area, and less frequently so in the temporal, parietal and central areas. Diffuse hypoperfusion of the frontal lobes (bilateral hypofrontality) was seen in 29% of patients in the Sjögren's group. An acetazolamide stress test was performed in seven patients. There was an increase in perfusion deficits in two patients, no change in two patients, and hypoperfusion decreased in three patients compared with baseline. The results indicate that most Sjögren's syndrome patients experience alterations in cerebral blood flow that are consistent with systemic lupus erythematosus, with heterogeneous reactivity to acetazolamide-induced hypercapnia. These alterations present as focal perfusion deficits and bilateral diffuse hypoperfusion of the lobes. The mechanism of cerebral blood flow alterations is unknown, although it might be the result of diffuse cerebral vasculitis.

Ecological study of effect of breast feeding on infant mortality in Latin America.

OBJECTIVE: To estimate the effect of exclusive breast feeding and partial breast feeding on infant mortality from diarrhoeal disease and acute respiratory infections in Latin America. DESIGN: Attributable fraction analysis of national data on infant mortality and breast feeding. SETTING: Latin America and the Caribbean. MAIN OUTCOME MEASURES: Mortality from diarrhoeal disease and acute respiratory infections and nationally representative breastfeeding rates. RESULTS: 55% of infant deaths from diarrhoeal disease and acute respiratory infections in Latin America are preventable by exclusive breast feeding among infants aged 0-3 months and partial breast feeding throughout the remainder of infancy. Among infants aged 0-3 months, 66% of deaths from these causes are preventable by exclusive breast feeding; among infants aged 4-11 months, 32% of such deaths are preventable by partial breast feeding. 13.9% of infant deaths from all causes are preventable by these breastfeeding patterns. The annual number of preventable deaths is about 52 000 for the region. CONCLUSIONS: Exclusive breast feeding of infants aged 0-3 months and partial breast feeding throughout the remainder of infancy could substantially reduce infant mortality in Latin America. Interventions to promote breast feeding should target younger infants.

Comparative efficiency of national health systems: cross national econometric analysis.

OBJECTIVE: To improve the evidence base for health policy by devising a method to measure and monitor the performance of health systems. DESIGN: Estimation of the relation between levels of population health and the inputs used to produce health. SETTING: 191 countries. MAIN OUTCOME MEASURE: Health system efficiency (performance). RESULTS: Estimated efficiency varied from nearly fully efficient to nearly fully inefficient. Countries with a history of civil conflict or high prevalence of HIV and AIDS were less efficient. Performance increased with health expenditure per capita. CONCLUSIONS: Increasing the resources for health systems is critical to improving health in poor countries, but important gains can be made in most countries by using existing resources more efficiently.

Technetium-99mTc-HMPAO brain SPECT in antiphospholipid syndrome--preliminary data.

BACKGROUND: Antiphospholipid syndrome (APS) is defined as the presence of repeated episodes of arterial or venous thrombosis, recurrent spontaneous abortions and thrombocytopenia in patients with elevated antiphospholipid antibodies. An important feature of APS are cerebrovascular disorders of thrombotic origin. The aim of the study was to assess cerebral blood flow changes utilising brain SPECT HMPAO scanning. METHODS: Brain SPECT (99m)Tc-HMPAO scanning was performed in 20 patients with APS: 12 with systemic lupus erythematosus, 4 with Sneddon's syndrome, 2 with Sjögren's syndrome, 2 with primary APS. 30 healthy volunteers served as a control group. RESULTS: 19 studies were abnormal, 1 normal. Abnormalities consisted of multifocal perfusion deficits and diffuse decrease of regional blood flow. The average number of focal perfusion deficits was 4.8 +/- 1.7. In 7 patients diffuse hypoperfusion of frontal lobes was seen, in 1 patient additionally hypoperfusion of temporal and occipital lobes. There was a correlation between the number of focal perfusion deficits and cognitive impairment in this group of patients. Correlation between SPECT images and clinical data was moderate in cerebellar syndrome and paresis, weak in persistent headache and vertigo. CONCLUSIONS: Those results indicate the high utility of CBF brain SPECT scanning in antiphospholipid syndrome.

Factors in long-term marriages.

"The present study involves a nonrandom sample of 351 [U.S.] couples who have been married 15 years or more. Differences were found in the reported reasons for staying together between happy, unhappy, and mixed (one partner happy and one unhappy) marriages. For happy couples, the most frequently mentioned reasons for staying together was the perceived nature of the relationship, then the belief in marriage as a long-term commitment. Among the mixed and unhappy marriages, the most frequently named reason was the belief that marriage is a long-term commitment. Nineteen percent of those in mixed marriages and 47% in unhappy marriages said the children kept the marriage together."

Mutations in SDCCAG8/NPHP10 Cause Bardet-Biedl Syndrome and Are Associated with Penetrant Renal Disease and Absent Polydactyly.

The ciliopathies are an expanding group of disorders caused by mutations in genes implicated in the biogenesis and function of primary cilia. Bardet-Biedl syndrome (BBS) is a model ciliopathy characterized by progressive retinal degeneration, obesity, polydactyly, cognitive impairment, kidney anomalies and hypogonadism. Mutations in SDCCAG8(NPHP10) were described recently in patients with nephronophthisis and retinal degeneration (Senior-Loken syndrome; SLS). Given the phenotypic and genetic overlap between known ciliopathy genes, we hypothesized that mutations in SDCCAG8 might also contribute alleles to more severe, multisystemic ciliopathies. We performed genetic and phenotypic analyses of 2 independent BBS cohorts. Subsequent to mutation screening, we made a detailed phenotypic analysis of 5 families mutated for SDCCAG8 (3 homozygous and 2 compound heterozygous mutations) and conducted statistical analyses across both cohorts to examine possible phenotype-genotype correlations with mutations at this locus. All patients with mutations in SDCCAG8 fulfilled the diagnostic criteria for BBS (retinal degeneration, obesity, cognitive defects, renal failure, hypogonadism). Interestingly, none of the patients with primary SDCCAG8 mutations had polydactyly, a frequent but not obligatory BBS feature. In contrast, the same patients displayed early-onset renal failure, obesity, as well as recurrent pulmonary and ENT infections. Comparison of the phenotypes of these families with our entire BBS cohort indicated that renal impairment and absent polydactyly correlated significantly with causal SDCCAG8 mutations. Thus, SDCCAG8 mutations are sufficient to cause BBS in 1-2% of our combined cohorts, and define this gene as the sixteenth BBS locus (BBS16). The absence of polydactyly and the concomitant, apparently fully penetrant association with early kidney failure represents the first significant genotype-phenotype correlation in BBS that potentially represents an indicator for phenotype-driven priority screening and informs specific patient management.