Enhancing r1 Relaxivity in GdDOTA-Monoamide Complexes through Polar Group-Mediated Ordering of Second-Sphere Water Molecules.

This study was designed to test whether the single appended phosphonate group in GdDOTA-1AmP is sufficient for catalyzing the exchange of proton from the single inner-sphere water-exchanging molecule. Unlike the other phosphonate derivatives in this series, GdDOTA-1AmP showed a surprisingly smooth increase in r1 relaxivity from 3.0 to 6.3 mM-1 s-1 at 20 MHz as the pH was lowered from 9 to 2.5. In comparison to the bis-, tris-, and tetrakis-phosphonate analogues, which all show a biphasic dependence of r1 with changes in pH, the unique r1 versus pH characteristics of GdDOTA-1AmP are shown to closely parallel deprotonation of the single appended phosphonate group. Although the tissue biodistribution and clearance rates of GdDOTA-1AmP are more favorable than the other more highly charged phosphonate derivatives, the pH dependency of r1 is substantially reduced at magnetic fields typically used for small animal imaging (7 and 9.4T), so the attractiveness of this new molecule for quantitative imaging of tissue pH is diminished. However, this study provides some new insights into the feasibility of designing pH-responsive MRI contrast agents based upon fundamental acid-base prototropic mechanisms.

StereoPHIP: Stereoselective Parahydrogen-Induced Polarization.

Parahydrogen-induced polarization (PHIP) followed by polarization transfer to 13 C is a rapidly developing technique for the generation of 13 C-hyperpolarized substrates. Chirality plays an essential role in living systems and differential metabolism of enantiomeric pairs of metabolic substrates is well documented. Inspired by asymmetric hydrogenation, here we report stereoPHIP, which involves the addition of parahydrogen to a prochiral substrate with a chiral catalyst followed by polarization transfer to 13 C spins. We demonstrate that parahydrogen could be rapidly added to the prochiral precursor to both enantiomers of lactic acid (D and L), with both the (R,R) and (S,S) enantiomers of a chiral rhodium(I) catalyst to afford highly 13 C-hyperpolarized (over 20 %) L- and D-lactate ester derivatives, respectively, with excellent stereoselectivity. We also show that the hyperpolarized 1 H signal decays obtained with the (R,R) and (S,S) catalysts were markedly different. StereoPHIP expands the scope of conventional PHIP to the production of 13 C hyperpolarized chiral substrates with high stereoselectivity.

Identifying dementia using medical data linkage in a longitudinal cohort study: Lothian Birth Cohort 1936.

BACKGROUND: The Lothian Birth Cohort 1936 (LBC1936) is a longitudinal study of ageing with well-characterised assessments, but until now, it has relied on self-report or proxies for dementia such as cognitive tests. Our aims were twofold: a) to describe a framework for identifying dementia in a cohort study. b) to report the age-specific incidence and prevalence of all-cause dementia and dementia subtypes in 865 individuals in the LBC1936. METHODS: Electronic Health Records (EHR) of all participants were reviewed, and relevant information was extracted to form case vignettes for everyone with any record of cognitive dysfunction. The EHR data sources include hospital and clinic letters, general practitioner and hospital referrals, prescribed medications, imaging and laboratory results. Death certificate data were obtained separately. Clinician assessments were performed when there was concern about a participant's cognition. A diagnosis of probable dementia, possible dementia, or no dementia was agreed upon by a consensus diagnostic review board, comprised of a multidisciplinary team of clinical dementia experts who reviewed case vignettes and clinician assessment letters. For those with probable dementia, a subtype was also determined, where possible. We compared the agreement between our newly ascertained dementia diagnoses with the existing self-reported dementia diagnoses. RESULTS: Self-reported dementia diagnoses were positive in only 17.8% of ascertained dementia diagnoses. The EHR review identified 163/865 (18.8%) individuals as having cognitive dysfunction. At the consensus diagnostic review board, 118/163 were diagnosed with probable all-cause dementia, a prevalence of 13.6%. Age-specific dementia prevalence increased with age from 0.8% (65-74.9 years) to 9.93% (85-89.9 years). Prevalence rates for women were higher in nearly all age groups. The most common subtype was dementia due to Alzheimer disease (49.2%), followed by mixed Alzheimer and cerebrovascular disease (17.0%), dementia of unknown or unspecified cause (16.1%), and dementia due to vascular disease (8.5%). CONCLUSIONS: We present a robust systematic framework and guide for other cohort teams wanting to ascertain dementia diagnoses. The newly ascertained dementia diagnosis provides vital data for further analyses of LBC1936 to allow exploration of lifecourse predictors of dementia.

Integrating the MasSpec Pen with Sub-Atmospheric Pressure Chemical Ionization for Rapid Chemical Analysis and Forensic Applications.

Analytical methods that allow rapid, sensitive, and specific chemical measurements are central to forensic analysis and essential to accelerating compound screening and confirmation. We have previously reported the development of the MasSpec Pen technology as an easy-to-use and disposable hand-held device integrated to a mass spectrometer for direct analysis and molecular profiling of biological samples. In this Technical Note, we describe a new apparatus that integrates the MasSpec Pen device with a subatmospheric pressure chemical ionization (sub-APCI) source and an ion trap mass spectrometer for detection and semiquantitative analysis of forensic-related compounds. Coupling the MasSpec Pen device to a sub-APCI source allowed semiquantitative analysis of the drugs cocaine and oxycodone, the agrochemicals atrazine and azoxystrobin, and the explosives trinitrotoluene and dinitroglycerin in under 20 s. Using chemical ionization, improved reproducibility and sensitivity for targeted chemical detection and compound identification was achieved while maintaining the user-friendly features of the hand-held MasSpec Pen device. Limits of detection in the high picogram to low nanogram range were obtained for the compounds analyzed, which are within the range of federal screening cutoffs and those reported for other ambient ionization MS techniques. Altogether, the MasSpec Pen sub-APCI system described enabled rapid and semiquantitative chemical analysis for forensic applications and could be further adapted and applied to other areas of chemical testing.

Use of Biologic Extracellular Matrix in Two Ways to Reduce Cardiac Electronic Device Infection.

Cardiac implantable electronic device (CIED) infections are a serious complication of both initial device implants and generator change procedures, and they are associated with a wide range of presentations. Reported rates of CIED infections vary widely from 0.1% to 19.9%, but it is estimated that they occur in 0.5% of initial device implants and 1-7% of subsequent implants. It is widely accepted that the administration of local antibiotics within the pocket as well as extracellular matrices (ECMs) can be utilized to reduce the incidence of CIED infections. We describe a case where the use of an additional biological ECM scaffold sutured directly into the incision site was utilized in addition to a biological ECM pouch in order to reduce the risk of infection. We propose that biological ECM could be utilized to reinforce the incision site directly as well as ECM within the pocket to reduce the instances of CIED infections. Further investigation of the use of biological ECM to prevent infection is warranted and paramount to further decrease the number of complications associated with device implantation.

Machine-Learning Modeling to Predict Hospital Readmission Following Discharge to Post-Acute Care.

OBJECTIVES: Primary purpose was to generate a model to identify key factors relevant to acute care hospital readmission within 90 days from 3 types of post-acute care (PAC) sites: home with home care services (HC), skilled nursing facility (SNF), and inpatient rehabilitation facility (IRF). Specific aims were to (1) examine demographic characteristics of adults discharged to 3 types of PAC sites and (2) compare 90-day acute hospital readmission rate across PAC sites and risk levels. DESIGN: Retrospective, secondary analysis design was used to examine hospital readmissions within 90 days for persons discharged from hospital to SNF, IRF, or HC. SETTINGS AND PARTICIPANTS: Cohort sample was composed of 2015 assessment data from 3,592,995 Medicare beneficiaries, including 1,536,908 from SNFs, 306,878 from IRFs, and 1,749,209 patients receiving HC services. MEASURES: Initial level of analysis created multiple patient profiles based on predictive patient characteristics. Second level of analysis consisted of multiple logistic regressions within each profile to create predictive algorithms for likelihood of readmission within 90 days, based on risk profile and PAC site. RESULTS: Total sample 90-day hospital readmission rate was 27.48%. Patients discharged to IRF had the lowest readmission rate (23.34%); those receiving HC services had the highest rate (31.33%). Creation of model risk subgroups, however, revealed alternative outcomes. Patients seem to do best (i.e., lowest readmission rates) when discharged to SNF with one exception, those in the very high risk group. Among all patients in the low-, intermediate-, and high-risk groups, the lowest readmission rates occurred among SNF patients. CONCLUSIONS AND IMPLICATIONS: The proposed model has potential use to stratify patients' potential risk for readmission as well as optimal PAC destination. Machine-learning modeling with large data sets is a useful strategy to increase the precision accuracy in predicting outcomes among patients who have nonhome discharges from the hospital.

Assessing predictors of respiratory tract infections in infants born to teenage mothers: secondary analysis of the Building Blocks trial data.

BACKGROUND: Respiratory tract infections (RTIs) are estimated to account for 60% of infants' primary care visits. There is limited research into risk factors for infant RTIs in those born to teenage mothers. AIMS: To identify risk factors for primary and secondary care RTI attendances, in infants of teenage mothers, and to identify risk factors associated with high primary care RTI consultations. METHOD: Secondary analysis of a data set from the Building Blocks trial of special home visiting support in England containing 1510 infants born to teenage mothers recruited to the study. Maternally reported and routinely collected data were examined. Multivariable logistic regression models were performed to determine independent predictors. Primary care data analysis also focused on infant risk factors for RTI consultation. RESULTS: No independently predictive risk factors for infant RTI were identified in primary care. Lower maternal antenatal attendances (odds ratio = 0.96, 95% confidence interval = 0.92-0.99), infants born in autumn (vs. spring; 0.54, 0.36-0.80) and neonatal unit (NNU) admissions (0.51, 0.30-0.89) had increased odds of attending accidents and emergencies with an RTI. Male infants (1.52, 1.03-2.25), NNU admissions (3.21, 1.98-5.22) and birth season had increased odds of RTI-associated hospital admissions. High infant RTI primary care consulters were more likely to have an RTI-associated hospital admission (2.11, 1.17-3.81) and less likely to have breastfed (0.55, 0.38-0.78). CONCLUSION: Risk factors previously found to increase the risk of an RTI infant admission in the broader population have been identified here. This study is one of the first to identify modifiable risk factors of high primary care RTI consulters.

Focus groups: the lived experience of participants with multiple sclerosis.

Multiple sclerosis (MS) is a chronic disease affecting young adults. The presence of the sometimes-invisible symptoms (loss of vision, fatigue, incontinence) and the episodic nature and uncertainty of symptoms can create a constant sense of vigilance or support the use of denial. Indeed, family, friends, and even nursing support may be elusive, leaving one feeling lonely, frightened, and insecure. The purposes of this research were to investigate the lived experiences of people with MS and examine their needs from their perspectives. Two focus groups included 4 men diagnosed with MS from 2 to 15 years and 6 women diagnosed with MS from 1.5 to 15 years. Four themes were identified. The first theme resonated around feelings that "nobody listened." The second theme, symptom devastation, described the overwhelming presence of symptoms and the difficulty they caused. The third theme was "picking and choosing," or making choices to maintain some control. "Fight your own fight" with self-advocacy and taking charge was the final theme. Even though MS continuously caused challenges and changes interfering with goals, participants described creative solutions. They learned to deal with the denial, refocus their priorities, plan their activities, and choose carefully. They described a litany of being unheard, unimportant, and confused, which led to feelings of dejection, desperation, and depression. Their most poignant need was someone to listen and teach since they identified knowledge as power. The data gathered contribute to knowledge and understanding of people living with MS. Findings support nursing interventions that empower and teach self-management techniques.