The contamination of surface water and ground water by human activities, such as fossil fuel extraction and agriculture, can be difficult to assess due to incomplete knowledge of the chemicals and chemistry involved. This is particularly true for the potential contamination of drinking water by nearby extraction of oil and/or gas from wells completed by hydraulic fracturing. A case that has attracted considerable attention is unconventional natural gas extraction in Susquehanna County, Pennsylvania, particularly around Dimock, Pennsylvania. We analyzed surface water and groundwater samples collected throughout Susquehanna County with complementary biological assays and high-resolution mass spectrometry. We found that Ah receptor activity was associated with proximity to impaired gas wells. We also identified certain chemicals, including disclosed hydraulic fracturing fluid additives, in samples that were either in close proximity to impaired gas wells or that exhibited a biological effect. In addition to correlations with drilling activity, the biological assays and high-resolution mass spectrometry detected substances that arose from other anthropogenic sources. Our complementary approach provides a more comprehensive picture of water quality by considering both biological effects and a broad screening for chemical contaminants.

Public health concerns related to the expansion of unconventional oil and gas drilling have sparked intense debate. In 2012, we published case reports of animals and humans affected by nearby drilling operations. Because of the potential for long-term effects of even low doses of environmental toxicants and the cumulative impact of exposures of multiple chemicals by multiple routes of exposure, a longitudinal study of these cases is necessary. Twenty-one cases from five states were followed longitudinally; the follow-up period averaged 25 months. In addition to humans, cases involved food animals, companion animals and wildlife. More than half of all exposures were related to drilling and hydraulic fracturing operations; these decreased slightly over time. More than a third of all exposures were associated with wastewater, processing and production operations; these exposures increased slightly over time. Health impacts decreased for families and animals moving from intensively drilled areas or remaining in areas where drilling activity decreased. In cases of families remaining in the same area and for which drilling activity either remained the same or increased, no change in health impacts was observed. Over the course of the study, the distribution of symptoms was unchanged for humans and companion animals, but in food animals, reproductive problems decreased and both respiratory and growth problems increased. This longitudinal case study illustrates the importance of obtaining detailed epidemiological data on the long-term health effects of multiple chemical exposures and multiple routes of exposure that are characteristic of the environmental impacts of unconventional drilling operations.

This is an interview conducted with an oil and gas worker who was employed in the industry from 1993 to 2012. He requested that his name not be used. From 2008 to 2012, he drilled wells for a major operator in Bradford County, Pennsylvania. Bradford County is the center of the Marcellus shale gas boom in Northeastern Pennsylvania. In 2012, he formed a consulting business to assist clients who need information on the details of gas and oil drilling operations. In this interview, the worker describes the benefits and difficulties of the hard work involved in drilling unconventional gas wells in Pennsylvania. In particular, he outlines the safety procedures that were in place and how they sometimes failed, leading to workplace injuries. He provides a compelling view of the trade-offs between the economic opportunities of working on a rig and the dangers and stresses of working long hours under hazardous conditions.

Environmental concerns surrounding drilling for gas are intense due to expansion of shale gas drilling operations. Controversy surrounding the impact of drilling on air and water quality has pitted industry and leaseholders against individuals and groups concerned with environmental protection and public health. Because animals often are exposed continually to air, soil, and groundwater and have more frequent reproductive cycles, animals can be used as sentinels to monitor impacts to human health. This study involved interviews with animal owners who live near gas drilling operations. The findings illustrate which aspects of the drilling process may lead to health problems and suggest modifications that would lessen but not eliminate impacts. Complete evidence regarding health impacts of gas drilling cannot be obtained due to incomplete testing and disclosure of chemicals, and nondisclosure agreements. Without rigorous scientific studies, the gas drilling boom sweeping the world will remain an uncontrolled health experiment on an enormous scale.

OBJECTIVETo determine trends in behavior diagnoses; assess the relationship between diagnoses and age, sex, reproductive status, and breed; and evaluate associations between diagnoses within the same dog (comorbidity).DESIGNRetrospective case series.ANIMALS1,644 dogs.PROCEDURESMedical records of dogs evaluated for behavioral problems were reviewed for breed, sex, reproductive status, consultation year, birth date, and diagnoses.RESULTSNumbers of dogs with aggression, anxiety, and unruly behavior increased over the course of the study, as did the total number of dogs evaluated for behavioral problems. In general and for aggression, Dalmatians, English Springer Spaniels, German Shepherd Dogs, and mixed-breed dogs were evaluated more often than expected, whereas Labrador Retrievers and Golden Retrievers were evaluated less often than expected. Labrador Retrievers were also underrepresented for anxiety, whereas mixed-breed dogs were overrepresented. Males were overrepresented except for interdog aggression, anxieties, and phobias, whereas females were overrepresented for phobias. Dogs with phobias were evaluated at a median age of 6.5 years, compared with dogs with other problems (median age, 2.5 years). A mean of 1.6 diagnoses/dog was observed, with certain diagnoses clustered.CONCLUSIONS AND CLINICAL RELEVANCEResults suggested that in dogs, behavioral problems changed over the course of the study; age, sex, and breed distributions varied among diagnoses; and certain diagnoses were likely to occur together.

Objective-To describe trends in behavior diagnoses from 1991 to 2001; assess the relationship between diagnoses and age, sex, reproductive status, and breed; and evaluate associations between diagnoses within the same cat (comorbidity).Design-Retrospective case series.Animals-736 cats.Procedures-Medical records were reviewed for species, breed, sex, reproductive status, consultation year, birth date, and diagnoses.Results-The caseload decreased over the course of the study. Aggression toward people increased, and spraying decreased. Cases involving Siamese cats decreased over time. Siamese cats were evaluated more often than expected in general and specifically for aggression and ingestive behavior problems, whereas Persian cats were evaluated more often than expected for elimination outside of the litter box. Domestic shorthair cats were evaluated less often than expected in general and specifically for aggression, ingestive behavior problems, and house soiling. Male cats were overrepresented. Cats with ingestive behavior problems were evaluated at a median age of 1.5 years, compared with cats with other problems (median age, 5.5 years). Certain diagnoses were clustered, with a mean of 1.2 diagnoses/cat.Conclusions and Clinical Relevance-Results suggested that in cats, behavior problems changed over the course of the study, age and breed distributions varied among diagnoses, and certain diagnoses were likely to occur together.

The solution structure of neuronal bungarotoxin (nBgt) has been studied by using two-dimensional 1H NMR spectroscopy. Sequence-specific assignments for over 95% of the backbone resonances and 85% of the side-chain resonances have been made by using a series of two-dimensional spectra at four temperatures. From these assignments over 75% of the NOESY spectrum has been assigned, which has in turn provided 582 distance constraints. Twenty-seven coupling constants (NH-alpha CH) were determined from the COSY spectra, which have provided dihedral angle constraints. In addition, hydrogen exchange experiments have suggested the probable position of hydrogen bonds. The NOE constraints, dihedral angle constraints, and the rates of amide proton exchange suggest that a triple-stranded antiparallel beta sheet is the major component of secondary structure, which includes 25% of the amino acid residues. A number of NOE peaks were observed that were inconsistent with the antiparallel beta-sheet structure. Because we have confirmed by sedimentation equilibrium that nBgt exists as a dimer, we have reinterpreted these NOE constraints as intermolecular interactions. These constraints suggest that the dimer consists of a six-stranded antiparallel beta sheet (three from each monomer), with residues 55-59 forming the dimer interface.

The recent demonstrations that thrombolytic therapy with plasminogen activators can result in substantial reductions in mortality from coronary thrombosis have generated considerable interest in the properties of fibrinolytic enzymes. Examination of the primary sequence of these proteins (which include tissue plasminogen activator, plasminogen, and urokinase) reveals that each is composed of a mosaic of domains which appear to be spatially distinct and connected by short peptide linkers. There is, however, little experimental information about the three-dimensional structure of any of the proteins, although several X-ray diffraction and NMR studies of isolated domains have been reported. Here we report two-dimensional NMR spectra of intact urokinase which are remarkably well resolved for a protein of this molecular weight. This effect is a consequence of substantial independent motion between individual domains of the protein, which overcomes the broadening effects anticipated for the slow overall tumbling rate of the intact molecule. As well as having significance for the physiological role of the protein, these results provide a direct means for the comparison of structural features determined for the isolated domains with those of the intact protein and may provide a basis for proposing or evaluating models for the overall structure of fibrinolytic proteins. Preliminary results with other proteins indicate that this approach may be generally applicable to other multidomain proteins of the fibrinolytic family.