Recent decreases in snow water storage in western North America.

Mountain snowpacks act as natural water towers, storing winter precipitation until summer months when downstream water demand is greatest. We introduce a Snow Storage Index (SSI), representing the temporal phase difference between daily precipitation and surface water inputs-sum of rainfall and snowmelt into terrestrial systems-weighted by relative magnitudes. Different from snow water equivalent or snow fraction, the SSI represents the degree to which the snowpack delays the timing and magnitude of surface water inputs relative to precipitation, a fundamental component of how snow water storage influences the hydrologic cycle. In western North America, annual SSI has decreased (p < 0.05) from 1950-2013 in over 25% of mountainous areas, as a result of substantially earlier snowmelt and rainfall in spring months, with additional declines in winter precipitation. The SSI and associated trends offer a new perspective on hydrologic sensitivity to climate change which have broad implications for water resources and ecosystems.

Spatial variation of the rain-snow temperature threshold across the Northern Hemisphere.

Despite the importance of precipitation phase to global hydroclimate simulations, many land surface models use spatially uniform air temperature thresholds to partition rain and snow. Here we show, through the analysis of a 29-year observational dataset (n = 17.8 million), that the air temperature at which rain and snow fall in equal frequency varies significantly across the Northern Hemisphere, averaging 1.0 °C and ranging from -0.4 to 2.4 °C for 95% of the stations. Continental climates generally exhibit the warmest rain-snow thresholds and maritime the coolest. Simulations show precipitation phase methods incorporating humidity perform better than air temperature-only methods, particularly at relative humidity values below saturation and air temperatures between 0.6 and 3.4 °C. We also present the first continuous Northern Hemisphere map of rain-snow thresholds, underlining the spatial variability of precipitation phase partitioning. These results suggest precipitation phase could be better predicted using humidity and air temperature in large-scale land surface model runs.

A Randomized Controlled Trial of the Collaborative Assessment and Management of Suicidality versus Enhanced Care as Usual With Suicidal Soldiers.

OBJECTIVE: This study describes a randomized controlled trial called "Operation Worth Living" (OWL) which compared the use of the Collaborative Assessment and Management of Suicidality (CAMS) to enhanced care as usual (E-CAU). We hypothesized that CAMS would be more effective than E-CAU for reducing suicidal ideation (SI) and suicide attempts (SA), along with secondary behavioral health and health care utilization markers for U.S. Army Soldier outpatients with significant SI (i.e., > 13 on Beck's Scale for Suicide Ideation). METHOD: Study participants were 148 Soldiers who presented to a military outpatient behavioral health clinic. There were 73 Soldiers in the experimental arm of the trial who received adherent CAMS; 75 Soldiers received E-CAU. Nine a-priori treatment outcomes (SI, past year SA, suicide-related emergency department (ED) admits, behavioral health-related ED admits, suicide-related inpatient psychiatric unit (IPU) days, behavioral health-related IPU days, mental health, psychiatric distress, resiliency) were measured through assessments at Baseline and at 1, 3, 6, and 12 months post-Baseline (with a 78% retention of intent-to-treat participants at 12 months). RESULTS: Soldiers in both arms of the trial responded to study treatments in terms of all primary and secondary outcomes (effect sizes ranged from 0.63 to 12.04). CAMS participants were significantly less likely to have any suicidal thoughts by 3 months in comparison to those in E-CAU (Cohen's d = 0.93, p=.028). CONCLUSIONS: Soldiers receiving CAMS and E-CAU significantly improved post-treatment. Those who received CAMS were less likely to report SI at 3 months; further group differences were not otherwise seen.

Relative Impact of Risk Factors, Thwarted Belongingness, and Perceived Burdensomeness on Suicidal Ideation in Veteran Service Members.

OBJECTIVE: We tested the associations between individualized risk factors, empirically validated constructs specific to suicide risk (i.e., thwarted belongingness and perceived burdensomeness, and two methods for conceptualizing suicidal ideation based on Suicide Index Score (SIS) and overall severity score of the Beck Scale for Suicide Ideation [BSS]). METHOD: The current study included a sample of 134 suicidal Veterans who were recruited from an inpatient psychiatry unit of a Veterans Affairs Medical Center. Participants completed the BSS, Interpersonal Needs Questionnaire, Outcome Questionnaire-45.2, Alcohol Use Disorder Identification Test, Drug Abuse Screening Test, and abbreviated versions of the Posttraumatic Stress Disorder Checklist-Military version (PCL-M) and Insomnia Severity Index. We used ordinary least squares regression with bootstrapping to conduct analyses due to the skewed distributions observed in the suicidal ideation outcomes. RESULTS: Thwarted belongingness was the only statistically significant correlate of the SIS, indicating a stronger desire to be dead than alive as Veterans perceived themselves as being increasingly disconnected and isolated from others (B = 0.36, standard error [SE] = 0.01, p = 0.005). In contrast, greater overall severity scores on the BSS were associated with higher ratings on the PCL-M (B = 0.21, SE = 0.07, p = 0.02) and for thwarted belongingness (B = 0.27, SE = 0.09, p = 0.04). Problematic alcohol use was significantly associated with lower overall severity scores (B = -.27, SE = 1.17, p < 0.001). CONCLUSION: Findings may inform clinical strategies for conceptualizing and targeting factors associated with suicidal risk.

Supporting Medical Students' Pursuit of Longitudinal Patient Experiences: Piloting an Innovative Visit Notification Tool at the Massachusetts General Hospital.

PROBLEM: Both medical educators and students have an increasing interest in longitudinal patient experiences (LPE) that allow students to work with patients at multiple points in time, often across multiple clinical settings. Despite this interest in LPE, following patients over time and across health systems remains a challenge. APPROACH: In August 2012-May 2013, with faculty support, two third-year medical students implemented a pilot program at the Massachusetts General Hospital (MGH) in the third-year block clerkship curriculum. One of the authors modified an existing novel, electronic visit notification tool (VNT) that integrates with the electronic medical record (EMR) to help students follow patients longitudinally. Students added patients to their cohort after obtaining the patient's verbal consent. Each week, the VNT sent students e-mails notifying them of all scheduled appointments for their cohort patients at all Partners HealthCare-affiliated sites. OUTCOMES: Each pilot student added approximately 20 patients to her cohort and followed 3-5 patients consistently. The pilot students felt the VNT made it significantly easier to follow patients over time, their appreciation of chronic illness care developed, and they gained a greater understanding of the integrated nature of patient care. NEXT STEPS: On the basis of student interest, the tool was made available to all MGH third-year students in March-May 2013 and offered to all MGH third-year students at the beginning of the next clinical year. Notification tools such as the VNT may enhance a hospital's existing EMR and facilitate longitudinal educational goals across all clinical clerkship models.

Raising the clinical standard of care for suicidal soldiers: an army process improvement initiative.

From 2004 to 2008, the suicide rate among US Army Soldiers increased 80%, reaching a record high in 2008 and surpassing the civilian rate for the first time in recorded history. In recent years, the rate of Army suicides rose again; the year 2012 reflects the highest rate of military suicides on record. There is a need to assess current behavioral health practices to identify both effective and ineffective practices, and to adapt services to meet the needs of the Army behavioral health patient population. This paper discusses a process improvement initiative developed in an effort to improve clinical processes for suicide risk mitigation in an Army behavioral health clinic located in the catchment area of the US Army Southern Regional Medical Command.

Assessing and treating different suicidal states in a danish outpatient sample.

The studies presented compare two methodologies for categorizing suicidal patients based on clinical data. Discussion follows regarding implications for risk assessment and treatment. In these studies, 52 outpatient subjects were placed into different groups based on coding their "suicidal motivation" (Study 1) and their "internal struggle" ratings (Study 2) using data collected at intake. Self-report ratings of 6 Suicide Status Form (SSF) Core Constructs (Psychological Pain, Stress, Agitation, Hopelessness, Self-Hate, and Overall Risk of Suicide) recorded both at intake and at completion of treatment were then compared to determine differences in Core Construct ratings among groups at different time points. In Study 1, overall differences among motivation groups (Life-motivated, Ambivalent, and Death-motivated) were significant for ratings at treatment completion of Overall Risk of Suicide, Self-Hate, and Psychological Pain. In Study 2, overall differences among groups (Wish to live, Ambivalent, and Wish to die) were significant for ratings at intake of Overall Risk of Suicide. At completion of treatment, overall differences among groups were significant for ratings of Overall Risk of Suicide, Hopelessness, and Self-Hate. In addition, significant interactions were found between test time and group for Overall Risk of Suicide and Self-Hate. Results suggest that categorizing suicidal patients by motivation and by the nature of their internal struggle could be beneficial to differential risk assessment with implications for clinical treatment.

Understanding and preventing military suicide.

The continual rise in the U.S. military's suicide rate since 2004 is one of the most vexing issues currently facing military leaders, mental health professionals, and suicide experts. Despite considerable efforts to address this problem, however, suicide rates have not decreased. The authors consider possible reasons for this frustrating reality, and question common assumptions and approaches to military suicide prevention. They further argue that suicide prevention efforts that more explicitly embrace the military culture and implement evidence-based strategies across the full spectrum of prevention and treatment could improve success. Several recommendations for augmenting current efforts to prevent military suicide are proposed.

Enhancing operational workflow and patient tracking in an ambulatory setting.

As Massachusetts General Hospital (MGH) was forging ahead with the completion of the new Yawkey Center for Outpatient Care, administrative groups began to struggle with how they would be able to function in the new building. They would be moving from smaller, isolated practice areas into much larger state-of-the-art facilities with shared common spaces. The affected practices were challenged with developing new workflows and communication processes. After an unsuccessful vendor search, teams from Partners/MGH Information Systems built a solution in-house, using the vendor search requirements as their functional specifications. The application, and the new building have been live since October 2004. The application now is managing 9,000 patients per appointments a day from all of the appointment scheduling systems used throughout the building. This case study will review how Massachusetts General used information systems to ensure success in its new 10-story ambulatory care center, and met the needs of clinicians, patients, staff, and practice managers.

Gas phase characterization of the noncovalent quaternary structure of cholera toxin and the cholera toxin B subunit pentamer.

Cholera toxin (CTx) is an AB5 cytotonic protein that has medical relevance in cholera and as a novel mucosal adjuvant. Here, we report an analysis of the noncovalent homopentameric complex of CTx B chain (CTx B5) using electrospray ionization triple quadrupole mass spectrometry and tandem mass spectrometry and the analysis of the noncovalent hexameric holotoxin usingelectrospray ionization time-of-flight mass spectrometry over a range of pH values that correlate with those encountered by this toxin after cellular uptake. We show that noncovalent interactions within the toxin assemblies were maintained under both acidic and neutral conditions in the gas phase. However, unlike the related Escherichia coli Shiga-like toxin B5 pentamer (SLTx B), the CTx B5 pentamer was stable at low pH, indicating that additional interactions must be present within the latter. Structural comparison of the CTx B monomer interface reveals an additional alpha-helix that is absent in the SLTx B monomer. In silico energy calculations support interactions between this helix and the adjacent monomer. These data provide insight into the apparent stabilization of CTx B relative to SLTx B.

Noncovalent Shiga-like toxin assemblies: characterization by means of mass spectrometry and tandem mass spectrometry.

Shiga-like toxin 1 (SLTx), produced by enterohemorrhagic strains of Escherichia coli (EHEC), belongs to a family of structurally and functionally related AB(5) protein toxins that are associated with human disease. EHEC infection often gives rise to hemolytic colitis, while toxin-induced kidney damage is one of the major causes of hemolytic uremic syndrome (HUS) and acute renal failure in children. As such, an understanding and analysis of the noncovalent interactions that maintain the quaternary structure of this toxin are fundamentally important since such interactions have significant biochemical and medical implications. This paper reports on the analysis of the noncovalent homopentameric complex of Shiga-like toxin B chain (SLTx-B(5)) using electrospray ionization (ESI) triple-quadrupole (QqQ) mass spectrometry (MS) and tandem mass spectrometry (MS/MS) and the analysis of the noncovalent hexameric holotoxin (SLTx-AB(5)) using ESI time-of-flight (TOF) MS. The triple-quadrupole analysis revealed highly charged monomer ions dissociate from the multiprotein complex to form dimer, trimer, and tetramer product ions, which were also seen to further dissociate. The ESI-TOFMS analysis of SLTx-AB(5) revealed the complex remained intact and was observed in the gas phase over a range of pHs. Theses findings demonstrate that the gas-phase structure observed for both the holotoxin and the isoloated B chains correlates well with the structures reported to exist in the solution phase for these proteins. Such analysis provides a rapid screening technique for assessing the noncovalent structure of this family of proteins and other structurally related toxins.

Analysis of a 17-amino acid residue, virus-neutralizing microantibody.

The antibody-binding site, through which an antibody binds to its epitope, is a complex structure formed by the folding together of six complementarity-determining regions (CDRs). However, certain peptides derived from CDR sequences retain antibody specificity and function; these are know as microantibodies (MicroAbs). For example, the F58 MicroAb is a 17 residue, cyclized peptide (CDLIYYDYEEDYYFDYC) derived from CDR-H3 of F58, an IgG1 specific for the gp120 envelope glycoprotein of human immunodeficiency virus type 1 (HIV-1). Both MicroAb and IgG recognize the same epitope in the V3 loop and, despite its small size, the MicroAb neutralizes the infectivity of HIV-1 IIIB only 32-fold less efficiently on a molar basis. The advantage of MicroAbs is that their small size facilitates structure-function analysis. Here, the F58 MicroAb was investigated using alanine scanning, mass spectroscopy and surface plasmon resonance. Neutralization of infectious IIIB was generally more sensitive to alanine substitution than binding to soluble gp120. There appeared to be a division of function within the MicroAb, with some residues involved in antigen binding (alanine substitution of 11D, 12Y or 13Y abrogated both binding and neutralization), whereas others were concerned solely with neutralization (substitution of 3L, 8Y or 14F abrogated neutralization, but not binding). The MicroAb is predominantly beta-sheet and has strong conformational constraints that are probably essential for activity. The MicroAb and soluble gp120 formed a 1 : 1 complex, with an association rate that was threefold greater than that with IgG and a faster dissociation rate. Its equilibrium dissociation constant is 37.5-fold greater than that of IgG, in line with neutralization data. This study demonstrates how MicroAbs can make a useful contribution to the understanding of antigen-antibody interactions.

Iron and copper chelation by flavonoids: an electrospray mass spectrometry study.

Flavonoids are well known as effective free radical scavengers exhibiting therefore an antioxidant behaviour. Another antioxidant mechanism however may result from the ability they have to chelate metal ions, rendering them inactive to participate in free radical generating reactions. Electrospray mass spectrometry has been used to study metal ion interactions with a set of flavonoids from different classes. Complexes with a range of stoichiometries, of metal: flavonoid, 1:1, 1:2, 2:2, 2:3 have been observed. The stoichiometry 1:2 is in general the preferred one. It is established for flavones and for the flavanone naringenin that the binding metal sites are preferentially at the 5-hydroxyl and 4-oxo groups. Redox reactions are also observed through the change of the oxidation state of the metal, jointly with the oxidation of the flavonoid by loss of hydrogen. Structures of the oxidized species of some flavonoids are proposed.

Interactions of flavonoids with iron and copper ions: a mechanism for their antioxidant activity.

The metal chelating properties of flavonoids suggest that they may play a role in metal-overload diseases and in all oxidative stress conditions involving a transition metal ion. A detailed study has been made of the ability of flavonoids to chelate iron (including Fe3+) and copper ions and its dependence of structure and pH. The acid medium may be important in some pathological conditions. In addition, the ability of flavonoids to reduce iron and copper ions and their activity-structure relationships were also investigated. To fulfill these objectives, flavones (apigenin, luteolin, kaempferol, quercetin, myricetin and rutin), isoflavones (daidzein and genistein), flavanones (taxifolin, naringenin and naringin) and a flavanol (catechin) were investigated. All flavonoids studied show higher reducing capacity for copper ions than for iron ions. The flavonoids with better Fe3+ reducing activity are those with a 2,3-double bond and possessing both the catechol group in the B-ring and the 3-hydroxyl group. The copper reducing activity seems to depend largely on the number of hydroxyl groups. The chelation studies were carried out by means of ultraviolet spectroscopy and electrospray ionisation mass spectrometry. Only flavones and the flavanol catechin interact with metal ions. At pH 7.4 and pH 5.5 all flavones studied appear to chelate Cu2+ at the same site, probably between the 5-hydroxyl and the 4-oxo groups. Myricetin and quercetin, however, at pH 7.4, appear to chelate Cu2+ additionally at the ortho-catechol group, the chelating site for catechin with Cu2+ at pH 7.4. Chelation studies of Fe3+ to flavonoids were investigated only at pH 5.5. Only myricetin and quercetin interact strongly with Fe3+, complexation probably occurring again between the 5-hydroxyl and the 4-oxo groups. Their behaviour can be explained by their ability to reduce Fe3+ at pH 5.5, suggesting that flavonoids reduce Fe3+ to Fe2+ before association.