High-Precision, Gas-Phase Hydrogen/Deuterium-Exchange Kinetics by Mass Spectrometry Enabled by Exchange Standards.

Mass spectrometry (MS) has become a primary tool for identifying and quantifying biological molecules. In combination with other orthogonal techniques, such as gas-phase hydrogen/deuterium exchange (gHDX), MS is also capable of probing the structure of ions. However, gHDX kinetics can depend strongly on many factors, including laboratory temperature, instrumental conditions, and instrument platform selection. These effects can lead to high variability with gHDX measurements, which has hindered the broader adoption of gHDX for structural MS. Here we introduce an approach for standardizing gHDX measurements using cosampled standards. Quantifying the exchange kinetics for analytes relative to the exchange kinetics of the standards results in greater accuracy and precision than the underlying absolute measurements. The standardization was found to be effective for several types of analytes including small molecules and intact proteins. A subset of analytes showed deviations in their standardized exchange profiles that are attributed to field heating and the concomitant conformational isomerization. Inclusion of helium during the gHDX process for collisional cooling helps mitigate such variations in exchange kinetics related to ion heating. We anticipate that the outcomes of this research will enable the broader use of gHDX in MS-based workflows for molecular identification and isomer differentiation.

Gas-Phase Hydrogen/Deuterium Exchange for Distinguishing Isomeric Carbohydrate Ions.

The structural diversity of carbohydrates presents a major challenge for glycobiology and the analysis of glycoconjugates. Mass spectrometry has become a primary tool for glycan analysis thanks to its speed and sensitivity, but the information content regarding the glycan structure of protonated glycoconjugates is hindered by the inability to differentiate linkage and stereoisomers. Here, we examine a variety of protonated carbohydrate structures by gas-phase hydrogen/deuterium exchange (HDX) to discover that the exchange rates are distinct for isomeric carbohydrates with even subtle structural differences. By incorporating an internal exchange standard, HDX could effectively distinguish all linkage and stereoisomers that were examined and presents a mass spectrometry-based approach for glycan structural analysis with immense potential.

Collaboration in maternity care is achievable and practical.

BACKGROUND: Enhancing collaboration has been highlighted as a marker for future success in maternity care, although this suggestion comes with little methodological guidance. This study assessed the efficacy of a collaborative partnership between obstetric doctors and midwives providing Midwifery Group Practice (MGP) care. METHODS: A retrospective analysis was undertaken with notes from weekly case review meetings held between the obstetricians and midwives over a 12-month period; audio recordings and a prospective analysis of 16 meetings with verbal contributions of the different professions; the number and types of cases discussed and referred, medical records kept at these meetings and a professional satisfaction questionnaire. Consistency of care was measured against the Australian National Midwifery Guidelines for Consultation and Referral. RESULTS: Of the 337 women booked with MGP, 50% were discussed at least once. Of these, 35% were referred for consultation with an obstetrician. Women as 'Patients' were most commonly discussed, followed by educational discussions and anecdotes with equal verbal contributions from midwives and doctors. Plans for each case were recorded 97% of the time, and adhered to 90% of the time. A high level of consistency of care between similar cases (75% of the time) and with the consultation and referral guidelines (85% of the time) were achieved. Professional satisfaction with this model of care rated highly for both groups. CONCLUSION: Inter-professional collaboration between midwifery and obstetric staff is highly attainable within this model of care. This study reinforces the effectiveness of collaboration in the MGP model of care for women of all risk levels and should encourage other maternity care providers to consider adopting this collaborative model.

What makes an effective antismoking campaign - insights from the trenches.

OBJECTIVES: This paper describes traditionally effective approaches for anti-smoking mass media advertising and explores challenges and future directions for campaign planning. The changing characteristics of the current smoking population and media landscape are examined. Type of program or service: Anti-smoking mass media advertising campaigns. METHODS: We present a commentary on the established creative and media strategies proven to be effective in prompting quit attempts among smokers, discuss new challenges facing anti-smoking campaign managers today and propose considerations for the future. RESULTS: Although evidence of effective approaches for tobacco control messaging and execution remains clear, the media landscape in Australia has changed dramatically in recent years with some audiences moving away from frequent and heavy television consumption towards online platforms and digital media channels. In addition, as smoking rates continue to fall, characteristics of current smokers are becoming increasingly relevant considerations for anti-smoking messaging and placement within a media environment that is becoming more expensive and fragmented. Funding anti-smoking advertising at the levels required to effectively prompt and maintain smoking cessation remains a high priority considering the extensive social and economic costs of smoking. LESSONS LEARNT: Although it is known that hard-hitting, emotional and/or testimonial anti-smoking advertisements can be effective in prompting quit attempts, optimal media channel selection and media mix for reaching and engaging audience segments is dynamic in an ever-changing media landscape. Targeting media channels popular with lower socio-economic status (SES) smokers can efficiently achieve wide population exposure as well as effectively reaching population groups with higher smoking prevalence. A collaborative approach between health professionals, researchers, creative directors and media buyers is required to ensure advertising materials are communicating the right message for the audience, and that it is being delivered effectively.

Borderline Personality Features in Inpatients with Bipolar Disorder: Impact on Course and Machine Learning Model Use to Predict Rapid Readmission.

BACKGROUND: Earlier research indicated that nearly 20% of patients diagnosed with either bipolar disorder (BD) or borderline personality disorder (BPD) also met criteria for the other diagnosis. Yet limited data are available concerning the potential impact of co-occurring BPD and/or BPD features on the course or outcome in patients with BD. Therefore, this study examined this comorbidity utilizing the standardized Borderline Personality Questionnaire (BPQ). METHODS: This study involved 714 adult patients with a primary diagnosis of BD per DSM-IV criteria who were admitted to the psychiatric unit at an academic hospital in Houston, TX between July 2013 and July 2018. All patients completed the BPQ within 72 hours of admission. Statistical analysis was used to detect correlations between severity of BD, length of stay (LOS), and scores on the BPQ. A machine learning model was constructed to predict the parameters affecting patients' readmission rates within 30 days. RESULTS: Analysis revealed that the severity of certain BPD traits at baseline was associated with mood state and outcome measured by LOS. Inpatients with BD who were admitted during acute depressive episodes had significantly higher mean scores on 7 of the 9 BPQ subscales (P<0.05) compared with those admitted during acute manic episodes. Inpatients with BD with greater BPQ scores on 4 of the 9 BPQ subscales had significantly shorter LOS than those with lower BPQ scores (P<0.05). The machine learning model identified 6 variables as predictors for likelihood of 30-day readmission with a high sensitivity (83%), specificity (77%), and area under the receiver operating characteristic curve of 86%. CONCLUSIONS: Although preliminary, these results suggest that inpatients with BD who have higher levels of BPD features were more likely to have depressive rather than manic symptoms, fewer psychotic symptoms, and a shorter LOS. Moreover, machine learning models may be particularly valuable in identifying patients with BD who are at the highest risk for adverse consequences including rapid readmission.

Assessing Audience Members' Ability to Identify the Media Source of a Health Campaign Disseminated via Different Media.

Background: An important criterion for health campaign media selection is the ability to achieve campaign awareness among target audiences. However, existing campaign exposure metrics cannot be applied across both traditional and digital media, which complicates decision making. The present study assessed the validity of using self-report as a measure of the extent to which different types of media achieve campaign awareness to assist in determining appropriate media budget allocations. Methods: A quasi-experiment involving varying combinations of television, online video, and online display smoking cessation advertisements was conducted to determine whether audience members were able to accurately report the source of their exposure to the campaign. Results: Of the 719 Western Australian adults sampled (50% males, 50 females, 50% smokers, 50% non-smokers), 64% reported seeing the campaign in the previous 2 weeks. Of these, 91% reported seeing the advertisement on television, 8% on online video, and 21% on online display (respondents could select multiple media). Despite proportional scheduling of the three media over the discrete campaign periods, in most cases respondents assumed their exposure had occurred via television, regardless of the actual source of exposure. Conclusions: Among both smokers and non-smokers, television had primacy in memory regardless of the actual media used. As such, relying on self-reported recall is unlikely to constitute a reliable method of assessing target audience exposure to campaigns on different media where those media are all screen-based. The results highlight the need for alternative media effectiveness metrics that permit direct comparisons between traditional and digital media.

Comparing the Cost-Effectiveness of Campaigns Delivered via Various Combinations of Television and Online Media.

BACKGROUND: Reflecting the increasing prevalence of online media, many mass media health campaigns are now delivered using both television (TV) and online media formats. The aim of this study was to evaluate a smoking cessation mass media campaign according to the cost-effectiveness of the various combinations of TV and online media formats to inform future media buying decisions. METHODS: A quasi-experimental interrupted time series approach was employed. The campaign was delivered in seven 1-week bursts using TV, online video (OV), or online display (OD) (e.g., banner ads) formats in isolation and in various combinations over a 13-week period. Campaign bursts were separated by "off-weeks" in which no campaign materials were delivered. Assessed outcomes were the number of campaign response "events" recorded (campaign web page views, calls to a smoking cessation telephone service, and registrations for smoking cessation services). The cost-effectiveness of each individual and combined media format condition in terms of these outcome variables was calculated using attributed production and broadcasting costs. RESULTS: Overall, OD alone was found to be the most cost-effective means of achieving the nominated campaign outcomes, followed by a combination of OV and OD and a combination of TV and OV. The use of TV in isolation was the least cost-effective. CONCLUSION: The results of this evaluation indicate that online media constitute a promising means of enhancing the cost-effectiveness of smoking cessation campaigns. Future research assessing a broader range of outcomes, especially smoking cessation, is needed to provide a more comprehensive account of the cost-effectiveness of various campaign media.

Association of FGD1 polymorphisms with early-onset breast cancer.

Recent cancer studies have suggested that the faciogenital dysplasia 1 (FGD1) gene may play a role in the development of tumor cells. Somatic alterations in the FGD1 gene and increased Fgd1 protein expression have been observed in many breast tumor cases. The present study sequenced the FGD1 gene in tumor DNA from 46 breast cancer patients using Ion Torrent sequencing. Three synonymous polymorphisms and one missense polymorphism were detected with next-generation sequencing; however, no somatic mutations were observed. The Thr697 variant was identified in 18 patients with an average age at diagnosis of 55 years, which was a lower average age than patients without the polymorphism. In addition, a higher frequency of Thr697 was observed in African-American patients. The Pro712 was observed in 15 breast cancer patients with an average age of 58 years, and was observed as a haplotype with the Thr697 variant in 28% of the breast cancer patients studied. The missense polymorphism (Ala226Thr) was identified in a 40-year-old female patient who had a recurrence of cancer. These polymorphisms (Ala226Thr, Thr697 and Pro712) may be associated with an earlier onset of breast cancer.

Adopting a Sustainable Community of Practice Model when Developing a Service to Support Patients with Epidermolysis Bullosa (EB): A Stakeholder-Centered Approach.

OBJECTIVES: Epidermolysis bullosa (EB) is a rare, genetic skin condition that is complicated, distressing, and painful and permeates every aspect of patients' lives. Support services are essential for meeting the primary needs of patients and families living with EB; however, provision is challenged by many complex issues. In collaboration with the patient organization DEBRA Ireland, this research conducted an in-depth analysis of Irish healthcare support services for EB, with a view to moving towards an improved and sustainable care pathway. METHODS: A sustainable community of practice model (SCOP), as a core construct provided a simplified framework when studying this complex system. The research utilized mixed methods, comprising individual interviews, questionnaires, and a participatory action research workshop based on a soft systems approach. The study engaged patients, family members, service providers, and policy developers. RESULTS: Findings emphasized that the complexities of life with EB are more than 'skin deep'. The lived experience of stakeholders revealed many levels of emotion, both positive and heart-rending. Despite the positive efforts of specialists in this field, inadequacies to meet the primary needs of people with EB, such as bandages-fundamental for survival-were highlighted. Participants reported challenges relating to understanding patients' needs, access to consistent services within hospitals and the community, time constraints, and the strong emotions evoked by this severe and rare disease. CONCLUSIONS: The study identified several areas that can be targeted to bring about improvements in meeting primary needs. Education and research at public, policy, and practice levels need to be prioritized. It is imperative that citizens move beyond an awareness that EB exists and demonstrate a consciousness about the importance of advocating and enabling seamless and sustainable support services through collective action.

Endothelin-1-induced priming to capsaicin in young animals.

Endothelin-1 (ET-1) is a known algogen that causes acute pain and sensitization in humans and spontaneous nociceptive behaviors when injected into the periphery in rats. This study sought to examine the effect of ET-1 exposure in the neonatal period on subsequent contralateral capsaicin-induced secondary mechanical hyperalgesia. ET-1 or saline was injected into the left plantar hindpaw on postnatal day 7 (P7). On postnatal day 11 (P11), capsaicin cream or control lotion was applied to the right dorsum hind paw and mechanical paw withdrawal thresholds were measured in the plantar hind paw. In saline control males, P11 administration of capsaicin produced a secondary mechanical hyperalgesia that was still present at 2h. Neonatal priming with ET-1 did not alter the magnitude or the duration of secondary mechanical hyperalgesia in males. In contrast, in control females, P11 administration of capsaicin produced less than 40 min of mechanical hyperalgesia. Neonatal priming with ET-1 prolonged the duration of secondary mechanical hyperalgesia in females. Priming with ET-1 on P7 led to a significant increase in capsaicin-induced Fos expression in the dorsal horn of the spinal cord in both males and females compared to controls (p<0.001). These findings further suggest that pain in early life may alter future responses to painful stimuli at both the behavioral and neuronal level.