Faculty searches get a facelift.

Hiring committees address the glut of highly qualified applicants for faculty positions by experimenting with new evaluation methods and adapting their expectations for today's increasingly competitive academic environment.

Shifting ground for big data researchers.

To harness the strength of data sets growing by leaps and bounds every day, cultural norms in biomedical research are under pressure to change with the times.

Science on set.

Depictions of science in television and movies can affect individual health decisions, influence public policy, and inspire imagination. Practicing scientists who consult for the entertainment industry aim to help accurately communicate complex scientific topics, without forgetting that the story is king.

Education evolving: teaching biology online.

The rise of massive open online courses (MOOCs) is shaking up education. For science professors, the Internet offers new opportunities and technological tools to develop new materials, rethink curricula, and teach more effectively, benefiting students both on campus and on the web.

Science for sale: academic meets industry.

As research becomes increasingly interdisciplinary and the lines between academic and industrial pursuits blur, scientists on both sides of the fence are developing outsourcing models to build innovative collaborations and open funding opportunities.

Drop that pipette: science by design.

An unexpected collaboration between a synthetic biology lab at UCSF and a Palo Alto-based design firm is stirring up the way that research is conceived and conducted, by integrating innovation and "design thinking" into the scientific method.

Developmental cascade models linking contextual risks, parenting, and internalizing symptoms: A 17-year longitudinal study from early childhood to emerging adulthood.

Although internalizing problems are the most common forms of psychological distress among adolescents and young adults, they have precursors in multiple risk domains established during childhood. This study examined cascading risk pathways leading to depression and anxiety symptoms in emerging adulthood by integrating broad contextual (i.e., multiple contextual risks), parental (i.e., negative parenting), and child (i.e., internalizing behaviors) characteristics in early and middle childhood. We also compared common and differential pathways to depression and anxiety symptoms depending on the conceptualization of symptom outcomes (traditional symptom dimension vs. bifactor dimensional model). Participants were 235 children (109 girls) and their families. Data were collected at 3, 6, 10, and 19 years of child age, using multiple informants and contexts. Results from a symptom dimension approach indicated mediation pathways from early childhood risk factors to depression and anxiety symptoms in emerging adulthood, suggesting common and distinct risk processes between the two disorders. Results from a bifactor modeling approach indicated several indirect pathways leading to a general internalizing latent factor, but not to symptom-specific (i.e., depression, anxiety) latent factors. Our findings highlighted comparative analytic approaches to examining transactional processes associated with later internalizing symptoms and shed light on issues of early identification and prevention.

Do-not-resuscitate (DNR) status and major depressive disorder (MDD): Clinical association and hospitalization outcomes.

OBJECTIVES: To understand (1) the association of Major Depressive Disorder (MDD) and do-not-resuscitate (DNR) status among hospitalized patients and (2) the association of MDD and hospitalization outcomes among DNR patients. METHODS: This was a cross-sectional analysis of United States Healthcare Cost and Utilization Project, Nationwide Inpatient Sample data from 2009 to 2013 for patients >18 years. To address the first objective, we used multivariable logistic regression among all hospitalized patients to compute the adjusted odds ratio (aOR) of having DNR status if patients have active MDD of varying severities after controlling for age, sex, race, suicidal ideation, and Elixhauser Comorbidity Index. To address the second objective, we used multivariable regression among patients with DNR status to compute aOR of having hospitalization outcomes such as increased length of stay, higher total charges, leaving against medical advice, and mortality if patients have MDD. RESULTS: Among all hospitalizations, 2.3% had DNR status. There was an inverse association between severity of MDD and having DNR status. Relative to those without MDD, patients with moderate recurrent MDD episode (aOR 0.74 (95% confidence interval (CI): 0.65-0.85) and severe recurrent MDD episode (aOR of 0.42 (95% CI: 0.37-0.48)) were significantly less likely to have DNR status. Among DNR patients, those with all severities of MDD except mild single episode MDD were >40% less likely to die during hospitalization. Among DNR patients, patients with MDD had 0.7 day longer length of stay, and >$4,500 higher total charges. SIGNIFICANCE OF RESULTS: Patients are less likely to have DNR status if they have active MDD. Among patients with DNR status, those with MDD are less likely to die during hospitalization than those without MDD. With current practice, depression is not associated with increased likelihood of death due to foregoing resuscitation prematurely, though the exact mechanisms of these findings need further investigation.

Structural and kinetic mapping of side-chain exposure onto the protein energy landscape.

Identification and characterization of structural fluctuations that occur under native conditions is crucial for understanding protein folding and function, but such fluctuations are often rare and transient, making them difficult to study. Native-state hydrogen exchange (NSHX) has been a powerful tool for identifying such rarely populated conformations, but it generally reveals no information about the placement of these species along the folding reaction coordinate or the barriers separating them from the folded state and provides little insight into side-chain packing. To complement such studies, we have performed native-state alkyl-proton exchange, a method analogous to NSHX that monitors cysteine modification rather than backbone amide exchange, to examine the folding landscape of Escherichia coli ribonuclease H, a protein well characterized by hydrogen exchange. We have chosen experimental conditions such that the rate-limiting barrier acts as a kinetic partition: residues that become exposed only upon crossing the unfolding barrier are modified in the EX1 regime (alkylation rates report on the rate of unfolding), while those exposed on the native side of the barrier are modified predominantly in the EX2 regime (alkylation rates report on equilibrium populations). This kinetic partitioning allows for identification and placement of partially unfolded forms along the reaction coordinate. Using this approach we detect previously unidentified, rarely populated conformations residing on the native side of the barrier and identify side chains that are modified only upon crossing the unfolding barrier. Thus, in a single experiment under native conditions, both sides of the rate-limiting barrier are investigated.

Ecological Momentary Assessment of Youth Anxiety: Evaluation of Psychometrics for Use in Clinical Trials.

Background: Ecological momentary assessment (EMA) captures naturalistic experience in real time and holds promise to improve our understanding and treatment of youth psychopathology. While psychometric evaluation of EMA methods is crucial, particularly for use as a tool in clinical trials, research examining the reliability and validity of EMA items in youth is lacking. Method: This study evaluates EMA responses from 204 child and adolescent participants (M age = 12.54, 60.8% female), including 131 participants with an anxiety disorder and 73 participants with no psychiatric diagnosis. We assessed the within- and between-person variability, internal consistency, test-retest reliability, and convergent and discriminant validity of two EMA items probing anxiety symptoms; one positive affect item served as a comparison. Results: All psychometric properties of the anxiety items were at least satisfactory in youth with anxiety disorders. However, there was restricted variability and poor test-retest reliability in youth with no diagnosis. Discussion: These results might facilitate future clinical trials using EMA to investigate pediatric anxiety. Results also suggest that unique EMA items might be needed to reliably track anxiety in healthy youth. Future work should continue to examine the psychometric properties of EMA protocols before implementation in clinical trials. ClinicalTrials.gov identifier: NCT00018057.

Structural Brain Correlates of Childhood Inhibited Temperament: An ENIGMA-Anxiety Mega-analysis.

Temperament involves stable behavioral and emotional tendencies that differ between individuals, which can be first observed in infancy or early childhood and relate to behavior in many contexts and over many years.1 One of the most rigorously characterized temperament classifications relates to the tendency of individuals to avoid the unfamiliar and to withdraw from unfamiliar people, objects, and unexpected events. This temperament is referred to as behavioral inhibition or inhibited temperament (IT).2 IT is a moderately heritable trait1 that can be measured in multiple species.3 In humans, levels of IT can be quantified from the first year of life through direct behavioral observations or reports by caregivers or teachers. Similar approaches as well as self-report questionnaires on current and/or retrospective levels of IT1 can be used later in life.

Climate stability and societal decline on the margins of the Byzantine empire in the Negev Desert.

Understanding past human settlement of inhospitable regions is one of the most intriguing puzzles in archaeological research, with implications for more sustainable use of marginal regions today. During the Byzantine period in the 4th century CE, large settlements were established in the arid region of the Negev Desert, Israel, but it remains unclear why it did so, and why the settlements were abandoned three centuries later. Previous theories proposed that the Negev was a "green desert" in the early 1st millennium CE, and that the Byzantine Empire withdrew from this region due to a dramatic climatic downturn. In the absence of a local climate archive correlated to the Byzantine/Early Islamic transition, testing this theory has proven challenging. We use stable isotopic indicators of animal dietary and mobility patterns to assess the extent of the vegetative cover in the desert. By doing so, we aim to detect possible climatic fluctuations that may have led to the abandonment of the Byzantine settlements. The findings show that the Negev Desert was not greener during the time period under investigation than it is today and that the composition of the animals' diets, as well as their grazing mobility patterns, remained unchanged through the Byzantine/Early Islamic transition. Favoring a non-climatic explanation, we propose instead that the abandonment of the Negev Byzantine settlements was motivated by restructuring of the Empire's territorial priorities.

Exploring subdomain cooperativity in T4 lysozyme II: uncovering the C-terminal subdomain as a hidden intermediate in the kinetic folding pathway.

Intermediates along a protein's folding pathway can play an important role in its biology. Previous kinetics studies have revealed an early folding intermediate for T4 lysozyme, a small, well-characterized protein composed of an N-terminal and a C-terminal subdomain. Pulse-labeling hydrogen exchange studies suggest that residues from both subdomains contribute to the structure of this intermediate. On the other hand, equilibrium native state hydrogen experiments have revealed a high-energy, partially unfolded form of the protein that has an unstructured N-terminal subdomain and a structured C-terminal subdomain. To resolve this discrepancy between kinetics and equilibrium data, we performed detailed kinetics analyses of the folding and unfolding pathways of T4 lysozyme, as well as several point mutants and large-scale variants. The data support the argument for the presence of two distinct intermediates, one present on each side of the rate-limiting transition state barrier. The effects of circular permutation and site-specific mutations in the wild-type and circular permutant background, as well as a fragment containing just the C-terminal subdomain, support a model for the unfolding intermediate with an unfolded N-terminal and a folded C-terminal subdomain. Our results suggest that the partially unfolded form identified by native state hydrogen exchange resides on the folded side of the rate-limiting transition state and is, therefore, under most conditions, a "hidden" intermediate.

A Ruptured Ectopic Pregnancy Presenting with a Negative Urine Pregnancy Test.

A negative urine pregnancy test in the emergency department traditionally excludes the diagnosis of pregnancy. We report a rare case of ruptured ectopic pregnancy in a patient with a negative urine pregnancy test but with a serum beta-human chorionic gonadotropin (ß-hCG) of 10 mIU/mL. The patient developed hemoperitoneum and required laparoscopy by Obstetrics and Gynecology (OB/Gyn). This case highlights the fallibility of the urine pregnancy test in diagnosing early pregnancy.

Utilizing Chlamydia trachomatis IgG serology with HSG to diagnose tuboperitoneal-factor infertility.

To evaluate if Chlamydia trachomatis IgG serology combined with hysterosalpingography can make it easier to detect tuboperitoneal factor infertility, we conducted a chart review of 76 consecutive patients at an infertility practice at West Virginia University from 1999-2001. We checked the charts for results of Chlamydia trachomatis IgG serology, Hysterosalpingography (HSG) and laparoscopy. Results of these tests were reviewed along with age, parity, previous reproductive tract disease surgery and duration of infertility. Complete data was found on 32 of the 76 patients. Chlamydia serology in conjunction with the HSG had a sensitivity of 80% for tuboperitoneal factor (tubal obstruction or pelvic adhesions), and a specificity of 82.3%. The positive predictive value was 80% and the negative predictive value was 82%. Since Chlamdia trachomatis IgG serologic testing is non-invasive and relatively inexpensive, we recommend combining it with hysterosalpingography as an infertility work-up. More invasive testing such as laparoscopy may be postponed or completely eliminated.

Rugged single domain antibody detection elements for Bacillus anthracis spores and vegetative cells.

Significant efforts to develop both laboratory and field-based detection assays for an array of potential biological threats started well before the anthrax attacks of 2001 and have continued with renewed urgency following. While numerous assays and methods have been explored that are suitable for laboratory utilization, detection in the field is often complicated by requirements for functionality in austere environments, where limited cold-chain facilities exist. In an effort to overcome these assay limitations for Bacillus anthracis, one of the most recognizable threats, a series of single domain antibodies (sdAbs) were isolated from a phage display library prepared from immunized llamas. Characterization of target specificity, affinity, and thermal stability was conducted for six sdAb families isolated from rounds of selection against the bacterial spore. The protein target for all six sdAb families was determined to be the S-layer protein EA1, which is present in both vegetative cells and bacterial spores. All of the sdAbs examined exhibited a high degree of specificity for the target bacterium and its spore, with affinities in the nanomolar range, and the ability to refold into functional antigen-binding molecules following several rounds of thermal denaturation and refolding. This research demonstrates the capabilities of these sdAbs and their potential for integration into current and developing assays and biosensors.