Hydrochemical determination of source water contributions to Lake Lungo and Lake Ripasottile (central Italy)

Lake Lungo and Lake Ripasottile are two shallow (4-5 m) lakes located in the Rieti Basin, central Italy, that have been described previously as surface outcroppings of the groundwater table. In this work, the two lakes as well as springs and rivers that represent their potential source waters are characterized physio-chemically and isotopically, using a combination of environmental tracers. Temperature and pH were measured and water samples were analyzed for alkalinity, major ion concentration, and stable isotope (δ2H, δ18O, δ13C of dissolved inorganic carbon, and δ34S and δ18O of sulfate) composition. Chemical data were also investigated in terms of local meteorological data (air temperature, precipitation) to determine the sensitivity of lake parameters to changes in the surrounding environment. Groundwater represented by samples taken from Santa Susanna Spring was shown to be distinct with SO4 2- and Mg2+ content of 270 and 29 mg/L, respectively, and heavy sulfate isotopic composition (δ34S=15.2‰ and δ18O=10‰). Outflow from the Santa Susanna Spring enters Lake Ripasottile via a canal and both spring and lake water exhibits the same chemical distinctions and comparatively low seasonal variability. Major ion concentrations in Lake Lungo are similar to the Vicenna Riara Spring and are interpreted to represent the groundwater locally recharged within the plain. The δ13CDIC exhibit the same groupings as the other chemical parameters, providing supporting evidence of the source relationships. Lake Lungo exhibited exceptional ranges of δ13CDIC (±5‰) and δ2H, δ18O (±5 ‰ and ±7 ‰, respectively), attributed to sensitivity to seasonal changes. The hydrochemistry results, particularly major ion data, highlight how the two lakes, though geographically and morphologically similar, represent distinct hydrochemical facies. These data also show a different response in each lake to temperature and precipitation patterns in the basin that may be attributed to lake water retention time. The sensitivity of each lake to meteorological patterns can be used to understand the potential effects from long-term climate variability

Alcohol-related expectancies are associated with the D2 dopamine receptor and GABAa receptor B3 subunit genes

Molecular genetic research has identified promising markers of alcohol dependence, including alleles of the D2 dopamine receptor (DRD2) and the GABAA receptor ￢3 subunit (GABRB3) genes. Whether such genetic risk manifests itself in stronger alcohol-related outcome expectancies, or in difficulty resisting alcohol, is unknown. In the present study, A1+ (A1A1 and A1A2 genotypes) and A1- (A2A2 genotype) alleles of the DRD2 and G1+ (G1G1 and G1 non-G1 genotypes) and G1- (non-G1 non-G1 genotype) alleles of the GABRB3 were determined in a group of 56 medically-ill patients diagnosed with alcohol dependence. Mood-related Alcohol Expectancy (AE) and Drinking Refusal Self-Efficacy (DRSE) were assessed using the Drinking Expectancy Profile (Young and Oei, 1996). Patients with the DRD2 A1+ allele, compared to those with the DRD2 A1- allele, reported lower DRSE in situations of social pressure (p=. 009). Similarly, lower DRSE was reported under social pressure by patients with the GABRB3 G1+ allele when compared to those with the GABRB3 G1- allele (p=.027). Patients with the GABRB3 G1+ allele also revealed reduced DRSE in situations characterized by negative affect than patients with the GABRB3 G1- alleles (p=. 037). Patients carrying the GABRB3 G1+ allele showed stronger AE relating to negative affective change (for example, increased depression) than their GABRB3 G1- counterparts (p=. 006). Biological influence in the development of some classes of cognitions is hypothesized. The clinical implications, particularly with regard to patient-treatment matching and the development of an integrated psychological and pharmacogenetic approach are discussed

Spatial Dynamics and Expanded Vertical Niche of Blue Sharks in Oceanographic Fronts Reveal Habitat Targets for Conservation

Dramatic population declines among species of pelagic shark as a result of overfishing have been reported, with some species now at a fraction of their historical biomass. Advanced telemetry techniques enable tracking of spatial dynamics and behaviour, providing fundamental information on habitat preferences of threatened species to aid conservation. We tracked movements of the highest pelagic fisheries by-catch species, the blue shark Prionace glauca, in the North-east Atlantic using pop-off satellite-linked archival tags to determine the degree of space use linked to habitat and to examine vertical niche. Overall, blue sharks moved south-west of tagging sites (English Channel; southern Portugal), exhibiting pronounced site fidelity correlated with localized productive frontal areas, with estimated space-use patterns being significantly different from that of random walks. Tracked female sharks displayed behavioural variability in diel depth preferences, both within and between individuals. Diel depth use ranged from normal DVM (nDVM; dawn descent, dusk ascent), to reverse DVM (rDVM; dawn ascent, dusk descent), to behavioural patterns where no diel differences were apparent. Results showed that blue sharks occupy some of the most productive marine zones for extended periods and structure diel activity patterns across multiple spatio-temporal scales in response to particular habitat types. In so doing, sharks occupied an extraordinarily broad vertical depth range for their size (1.0–2.0 m fork length), from the surface into the bathypelagic realm (max. dive depth, 1160 m). The space-use patterns of blue sharks indicated they spend much of the time in areas where pelagic longlining activities are often highest, and in depth zones where these fisheries particularly target other species, which could account for the rapid declines recently reported for blue sharks in many parts of the world's oceans. Our results provide habitat targets for blue shark conservation that may also be relevant to other pelagic species

Identification and characterization of an irreversible inhibitor of CDK2

Irreversible inhibitors that modify cysteine or lysine residues within a protein kinase ATP binding site offer, through their distinctive mode of action, an alternative to ATP-competitive agents. 4-((6-(Cyclohexylmethoxy)- 9H-purin-2-yl)amino)benzenesulfonamide (NU6102) is a potent and selective ATP-competitive inhibitor of CDK2 in which the sulfonamide moiety is positioned close to a pair of lysine residues. Guided by the CDK2/NU6102 structure, we designed 6-(cyclohexylmethoxy)-N-(4-(vinylsulfonyl)phenyl)-9H-purin-2-amine (NU6300), which binds covalently to CDK2 as shown by a co-complex crystal structure. Acute incubation with NU6300 produced a durable inhibition of Rb phosphorylation in SKUT-1B cells, consistent with it acting as an irreversible CDK2 inhibitor. NU6300 is the first covalent CDK2 inhibitor to be described, and illustrates the potential of vinyl sulfones for the design of more potent and selective compounds

Level of Pain and Disability at Time of TKR across the Past 10 Years: Results from Two National Cohorts

Introduction: A recent analysis reported a growing numbers of younger US adults with knee pain consistent with osteoarthritis (OA), although parallel analyses of knee x-rays found no increase in the classic radiographic signs of OA. The accompanying editorial evoked the need to understand if surgeons are performing surgery at an earlier stage in the condition.1 We compared pre-operative demographic and symptom profiles of a national US cohort of OA patients undergoing primary total knee replacement (TKR) in 2011-2012 with a national US cohort of patients from 2000-2004 to evaluate change, if any, in the timing of surgery as measured by patient pain and function. Methods: Following informed consent, the 2011-2012 national research study collected comprehensive data including demographic, comorbidity, and patient-reported pain and physical function, from a national sample of TKR patients. Comparable data from a national sample collected by one implant manufacturer between 2000-2004 were analyzed. Descriptive statistics compared the demographic and symptom profiles of the two cohorts. Results: There were fewer females in the 2011-2012 cohort (n=2363) compared to the 2000-2004 cohort (n=7144) (61.62%, vs. 66.72%). The 2011-2012 cohort was younger than the 2000-2004 cohort (66.7 years, vs. 68.12 years) and had a lower mean BMI (31.5 vs 32.3). Pre-operative physical function scores (SF36/PCS) were 3 points higher in 2011-2012 than 2000-2004 (33.2 vs. 30.41). When compared to the national PCS norm of 50 (SD=10), TKR patients from both time periods reported pre-operative function levels almost 2 standard deviations below the national norm. There was no significant difference in terms of emotional health (SF36/MCS scores: 51.85 for the 2011-2012 cohort vs. 51.83 for the 2000-2004 cohort). Conclusion: Despite the significant growth in the use of primary TKR in the last decade, especially among younger patients, TKR patients continue to report significant disability at the time of surgery

Differential Burden of Musculoskeletal Pain in Blacks and Whites at the Time of Total Joint Replacement Surgery

Introduction: The existence of racial disparities in total knee (TKR) and hip (THR) replacement outcomes is well established. The role of musculoskeletal co-morbidities among black and white TKR patients at the time of surgery were investigated in a prospective cohort enrolled in the FORCE-TJR consortium of 131 surgeons in 22 US states. Materials & methods: Descriptive analyses were performed on 3,306 TKR and 2,439 THR patients. Data included sociodemographic factors (age, sex, race), BMI, comorbid conditions using the modified Charlson comorbidity scores, burden of musculoskeletal disease using the Knee/Hip injury and Osteoarthritis Outcome Score (KOOS/HOOS) in both knees and hips, emotional health based on the Short Form 36 (SF-36) Mental Component Score (MCS) and physical function based on the Physical Component Score (SF-36 PCS). Factors associated with pre-operative surgical joint pain and function were examined using multivariate stepwise linear regression models. Results: Compared to Whites, Blacks (143 hips and 201 knees) reported worse surgical joint pain (mean pain: 39.3 vs. 49.2 (hip); 43.4 vs. 53.2 (knee)), poorer surgical joint function (mean function: 38.9 vs. 45.7 (hip); 45.9 vs. 53.4 (knee)), poorer global function (mean PCS: 30.0 vs. 31.6 (hip); 31.3 vs. 33.1 (knee)), and more non-operative joints pain. (All p\u3c0.03). In adjusted multivariable models, differences at the time of surgery in surgical joint symptoms and global function were explained by differences in musculoskeletal pain in the hips, knees, and low back. Conclusion: Greater burden of musculoskeletal pain explains differences in pre-operative pain and function between Blacks and Whites and likely impacts rehabilitation and subsequent TJR outcomes

Differential burden of musculoskeletal pain in African Americans and whites patients at the time of total joint replacement surgery

Objective: African Americans patients have greater operative joint pain and functional limitation at the time of total joint replacement (TJR) compared to white patients. We examined the factors associated with this apparent disparity. Methods: A consecutive sample of 5745 patients with advanced knee and hip osteoarthritis [who elected to undergo TJR in 2011-201] reported, preoperatively, medical comorbidities, operative and non-operative hip/ knee pain using Hip and Knee Disability and Osteoarthritis Outcome Scores (HOOS/KOOS), function using Short Form 36 Physical Component Score (PCS). Total burden of musculoskeletal pain was quantified as moderate/severe pain in non-operative hip and knee joints and lumbar back pain using Oswestry Disability Index (ODI). Associations among race, medical co-morbidites (modified Charlson), total musculoskeletal pain burden, operative joint pain, and functional limitations were examined using multivariable regression models. Results:Compared to Whites, African Americans (143 hips and 201 knees) reported worse surgical joint pain (mean pain: 39.3 vs. 49.2 [hip]; 43.4 vs. 53.2 [knee]), poorer surgical joint function (mean function: 38.9 vs. 45.7 [hip]; 45.9 vs. 53.4 [knee]), poorer global function (mean PCS: 30.0 vs. 31.6 [hip]; 31.3 vs. 33.1 [knee]), and more non-operative joints pain (p Conclusions: Greater burden of musculoskeletal pain explains differences in pre-operative pain and function between African American and white patients and likely impacts rehabilitation and subsequent TJR outcomes

Greater Co-morbidity Burden is Associated with Greater Pain and Disability at Time of Total Knee Replacement Among African American Patients

Introduction: The existence of racial disparities in total joint replacement (TJR) care is well established based on Medicare and VA data.1,3 As compared to white patients, African American TJR patients have lower utilization rates, more pain, poorer function at the time of surgery, and higher post-operative complication rates.2,3 We analyzed a national prospective total knee replacement (TKR) cohort to further investigate patterns of medical and musculoskeletal co-morbidities among African American and white TKR patients. Methods: Descriptive analyses were performed on a national database (FORCE-TJR) of 3,313 TKR patients from 107 orthopedic surgeons. Data collected include patient sociodemographics (age, gender, race, education, insurance, household income, smoking status), modified Charlson co-morbidity scores, and pre-operative and post-operative pain and function scores (SF-36 PCS and MCS, WOMAC, KOOS/HOOS ADL score). To assess the total musculoskeletal pain burden, WOMAC pain scores were recorded for non-operative weight bearing joints as well as Oswestry low back pain scores. Multivariate models are in progress. Results: Preliminary descriptive analyses demonstrate a higher medical co-morbidity burden in African American TKR patients as compared to whites (COPD, DM, smoking), as well as worse baseline pain (mean WOMAC pain score = 43.46 vs. 52.92, p Conclusion: Preliminary results demonstrate significant differences in medical and musculoskeletal co-morbidities that correlate with poorer pain and function scores in African American patients at the time of TKR