Newborn screening for cystic fibrosis: Is there benefit for everyone?

Newborn screening for cystic fibrosis (CF) has become a widely accepted and endorsed public health strategy in economically developed countries, although there is little consensus on optimal screening methods and gene panels. Increasing understanding of CFTR genetics and consequent unpredictability of phenotypic and clinical outcomes lead to diagnostic uncertainty, and emergence of Cystic Fibrosis Screen Positive Inconclusive Diagnosis (CF-SPID). Many of these children are clinically well or have a mild phenotype yet may still experience the psychosocial impact of a CF diagnosis. This questions the role of newborn screening and how best to manage those it identifies with CF-SPID.

Landscape-scale conservation design across biotic realms: sequential integration of aquatic and terrestrial landscapes.

Systematic conservation planning has been used extensively throughout the world to identify important areas for maintaining biodiversity and functional ecosystems, and is well suited to address large-scale biodiversity conservation challenges of the twenty-first century. Systematic planning is necessary to bridge implementation, scale, and data gaps in a collaborative effort that recognizes competing land uses. Here, we developed a conservation planning process to identify and unify conservation priorities around the central and southern Appalachian Mountains as part of the Appalachian Landscape Conservation Cooperative (App LCC). Through a participatory framework and sequential, cross-realm integration in spatial optimization modeling we highlight lands and waters that together achieve joint conservation goals from LCC partners for the least cost. This process was driven by a synthesis of 26 multi-scaled conservation targets and optimized for simultaneous representation inside the program Marxan to account for roughly 25% of the LCC geography. We identify five conservation design elements covering critical ecological processes and patterns including interconnected regions as well as the broad landscapes between them. Elements were then subjected to a cumulative threats index for possible prioritization. The evaluation of these elements supports multi-scaled decision making within the LCC planning community through a participatory, dynamic, and iterative process.

Rasch analysis of alcohol abuse and dependence diagnostic criteria in persons with spinal cord injury.

STUDY DESIGN: Cross-sectional. OBJECTIVE: The objective of the study is to examine whether alcohol use disorders should be conceptualized categorically as abuse and dependence as in the 'Diagnostic and Statistical Manual of Mental Disorders' 4th edition or on a single continuum with mild to severe category ratings as in the 'Diagnostic and Statistical Manual of Mental Disorders' 5th edition in people with spinal cord injury (SCI). SETTING: United States of America. METHODS: Data from 379 individuals who sustained SCI either traumatically or non-traumatically after the age of 18 and were at least 1 year post injury. Rasch analyses used the alcohol abuse and dependence modules of the Structured Clinical Interview for DSM-IV-TR Axis I Disorders Non-patient Edition (SCID-I/NP). RESULTS: Fifty-seven percent (n=166) of the entire sample endorsed criteria for alcohol abuse, and 25% (n=65) endorsed criteria for alcohol dependence. Fit values were generally acceptable except for one item (for example, alcohol abuse criterion 2), suggesting that the items fit the expectation of unidimensionality. Examination of the principal components analysis did not provide support for unidimensionality. The item-person map illustrates poor targeting of items. CONCLUSIONS: Alcohol abuse and dependence criterion appear to reflect a unidimensional construct, a finding that supports a single latent construct or factor consistent with the DSM-5 diagnostic model.

Are intensive data collection methods in pain research feasible in those with physical disability? A study in persons with chronic pain and spinal cord injury.

PURPOSE: Intensive repeated measures data collection procedures, such as ecological momentary assessment (EMA) and end-of-day (EOD) diaries, are becoming more prominent in pain research. Existing data on the feasibility of such methods is encouraging; however, almost nothing is known about feasibility in clinical populations with significant physical disabilities. Research methodology feasibility is crucial to the inclusion of individuals with physical disability in pain research given the high prevalence and impact of pain in these populations. The aim of this study was to examine study compliance, protocol acceptability, and reactivity of intensive data collection methods in adults with chronic pain and spinal cord injury (SCI). METHODS: Secondary analysis of data from a 7-day EMA and EOD diary study in a sample of 131 community dwelling adults with SCI. RESULTS: Results showed rates of missing data ranged from 18.4 to 22.8% across measures. Participant compliance was related to time of day/presence of audible prompts, mobility aid use, race, and baseline levels of pain and pain interference, with more missing data at wake and bedtimes/no prompts, and for those who used hand-held mobility devices, identified as black/African American, and/or reported higher baseline pain and pain interference. Participants rated the study methodology as generally highly acceptable and expressed willingness to participate in similar studies of much longer duration. There was no evidence of reactivity, defined as temporal shifts in pain or pain interference ratings. CONCLUSIONS: Overall, intensive pain data collection is feasible in persons with SCI with no evidence that the methodology impacts pain intensity or pain interference ratings.

Utility of post-traumatic amnesia in predicting 1-year productivity following traumatic brain injury: comparison of the Russell and Mississippi PTA classification intervals.

BACKGROUND: Duration of post-traumatic amnesia (PTA) correlates with global outcomes and functional disability. Russell proposed the use of PTA duration intervals as an index for classification of traumatic brain injury (TBI) severity. Alternative duration-based schemata have been recently proposed as better predictors of outcome to the commonly cited Russell intervals. OBJECTIVE: Validate a TBI severity classification model (Mississippi intervals) of PTA duration anchored to late productivity outcome, and compare sensitivity against the Russell intervals. METHODS: Prospective observational data on TBI Model System participants (n=3846) with known or imputed PTA duration during acute hospitalisation. Productivity status at 1-year postinjury was used to compare predicted outcomes using the Mississippi and Russell classification intervals. Logistic regression model-generated curves were used to compare the performance of the classification intervals by assessing the area under the curve (AUC); the highest AUC represented the best-performing model. RESULTS: All severity variables evaluated were individually associated with return to productivity at 1 year (RTP1). Age was significantly associated with RTP1; however, younger patients had a different association than older patients. After adjustment for individually significant variables, the odds of RTP1 decrease by 14% with every additional week of PTA duration (95% CI 12% to 17%; p<0.0001). The AUC for the Russell intervals was significantly smaller than the Mississippi intervals. CONCLUSIONS: PTA duration is an important predictor of late productivity outcome after TBI. The Mississippi PTA interval classification model is a valid predictor of productivity at 1 year postinjury and provides a more sensitive categorisation of PTA values than the Russell intervals.

Predictors of well-being among significant others of persons with multiple sclerosis.

OBJECTIVE: To examine patient and significant other characteristics as predictors of significant other well-being. METHODS: A total of 74 persons with multiple sclerosis (MS) and their significant others participated. Executive functioning was measured using neuropsychological tests. Awareness of cognitive deficit was measured as the discrepancy between the patient's reports of their abilities and objective test results. Awareness of functional deficit was measured as the discrepancy between the patient's and significant other's reports of the patient's functional abilities. Patient neurobehavioral disturbance was measured using a significant-other rated questionnaire. Significant other perceived social support and well-being (ie, psychological distress, life satisfaction, and general health status) were assessed using questionnaires filled out by the significant other. RESULTS: Executive dysfunction, neurobehavioral disturbance, and lack of awareness of functional deficits in patients were associated with poor well-being outcomes; whereas, lack of awareness of cognitive deficits was only weakly related to well-being. Social support was associated with positive well-being outcomes. CONCLUSIONS: Diminished insight regarding functional limitations may increase significant others' supervisory burden as patients attempt activities independently, whereas lack of awareness of cognitive deficits may not be directly associated with behavior-relevant impairments that significant others find distressing. Social support appears to be a powerful aid in diffusing the distress among significant others of MS patients.

The effect of age on sciatic nerve block duration.

The physiologic changes that occur with advancing age and their effect on the duration of peripheral nerve blocks have yet to be defined. We prospectively studied the duration of sciatic nerve block using mepivacaine in younger and older patients. Eighty ASA physical status I-III patients, aged 18-35 (n = 40) or 55-80 (n = 40) yr, having outpatient knee arthroscopy with a femoral block and a standardized sciatic nerve block were enrolled; 37 in each group completed the study. All patients received a Labat sciatic nerve block using 20 mL of 1.0% mepivacaine with 0.1 mEq/mL sodium bicarbonate and 1:400,000 (2.5 microg/mL) epinephrine and a femoral nerve block. The duration of sensory block (sensation of pinprick, temperature, and vibration), motor block (plantar and dorsi flexion), and complete sensory and motor block in the sciatic nerve distribution of the operative extremity were measured. The time for complete return of both sensory and motor function was longer in the older group, 329 +/- 47 min compared with 306 +/- 46 min (mean +/- sd) in the younger group (P = 0.04). The difference was small under the conditions of this study and would not be perceived clinically. Age also increased the time to return of vibratory sensation (younger = 292 +/- 58 min, older = 257 +/- 50 min; P = 0.007). The other measurements did not differ between groups. We conclude that age may affect peripheral nerve blocks and that more investigation is needed to determine the pharmacologic, physiologic, and chronologic factors behind these findings.

Emotional and behavioral adjustment after traumatic brain injury.

OBJECTIVES: To examine emotional and behavioral adjustment and recovery over 1 year after traumatic brain injury (TBI), and to determine whether the difficulties, if present, are due to neurologic insult. DESIGN: Longitudinal evaluation of adjustment from 1 month to 1 year after injury. SETTING: Level I trauma center at a university hospital. PATIENTS: One hundred fifty-seven consecutively hospitalized adults with TBI and 125 trauma controls with other system injuries evaluated at 1 and 12 months after injury. MAIN OUTCOME MEASURES: Katz Adjustment Scale (KAS). RESULTS: The TBI group at 1 year follow-up demonstrated significant emotional and behavioral maladjustment, but such difficulties did not appear to be mediated by the brain injury, since the KAS scores for the TBI and trauma control groups were not significantly different. Those with moderate TBI reported greater difficulties than those with mild or severe injuries. Changes in adjustment over 1 year were common for both groups. Within the TBI group there was differential recovery: improvement in cognitive clarity, dysphoric mood, and emotional stability, but increased difficulties with anger management, antisocial behaviors, and self-monitoring. CONCLUSIONS: These results raise questions about commonly held beliefs that those with mild TBI report greater distress, and clarify some misconceptions regarding change in emotional and behavioral functioning over time.

Measures of executive functioning as predictors of functional ability and social integration in a rehabilitation sample.

OBJECTIVE: To examine the utility of executive function tests in predicting rehabilitation outcome. DESIGN: A prospective, descriptive study of the value of neuropsychologic and motor functioning measures in the prediction of functional outcome 6 months after acute rehabilitation. SETTING: A Midwestern, urban, university-affiliated rehabilitation hospital. PATIENTS: Ninety consecutive admissions to traumatic brain injury, orthopedic, and spinal cord injury units. Age of the participants ranged from 17 to 73. MAIN OUTCOME MEASURES: Community Integration Questionnaire (CIQ), Disability Rating Scale (DRS), SF-36 Health Survey. RESULTS: Canonical correlation analyses indicated that measures of executive functioning and verbal memory were strongly related to measures of functional outcome 6 months after rehabilitation, as measured by the DRS and the CIQ. In contrast, perceived health status as measured by the SF-36 was highly related to estimated premorbid IQ and modestly related to visuospatial impairment. CONCLUSIONS: Executive functioning, verbal memory, and estimated premorbid intelligence predict functional dependence after discharge from rehabilitation beyond information regarding basic sensory and motor skills. Moreover, there is a dissociation between measures of functional outcome, such that objective and behaviorally oriented measures of disability (CIQ and DRS) are strongly related to each other; however, they are not related to perceptions of general health status (SF-36).

Executive functioning and predictors of falls in the rehabilitation setting.

OBJECTIVE: To examine the incremental utility of executive function tests in the prediction of inpatient falls. DESIGN: Evaluation of neuropsychologic and medical risk factors for fall was completed at admission. Inpatient falls were tabulated following discharge. SETTING: A freestanding, urban rehabilitation hospital. PATIENTS: Ninety consecutive admissions to traumatic brain injury, orthopedic, and spinal cord injury wards. Age of the participants ranged from 17 to 73 years old. MAIN OUTCOME MEASURE: Incident reports of inpatient falls. RESULTS: Standard multiple regression analyses indicated that measures of executive functioning sensitive to self-monitoring accounted for unique variance in falls beyond that explained by age and functional motor ability as assessed by the Functional Independence Measure. Visuospatial functioning, although not directly related to falls, was a significant predictor in combination with measures of executive functioning. Together, these variables accounted for 30.3% of the variance in inpatient falls (multiple r = .55; p < .001). CONCLUSION: The findings suggest that the influence of motor and sensory impairments on falls are moderated, in part, by executive functioning. Patients with intact executive functioning are less likely to act in ways that could result in a fall; thus, aggressive fall prevention measures may be unnecessary. In contrast, executive dysfunction may signal the need for intervention, even among patients whose profiles are unremarkable with regard to traditional risk factors for fall.

Physical, psychological, and social outcomes in geriatric rehabilitation patients.

OBJECTIVE: Previous research studies that addressed the relationship between age and functional outcome had limited generalizability because of small sample size, lack of an urban population, and limited variables that do not allow for a complete investigation of social, cognitive, psychological, and medical factors in geriatric rehabilitation. The present study attempted to assess the relationship between decade of geriatric life (60s, 70s, 80s, and 90+) and functional outcome. DESIGN: Survey study of geriatric cohorts. SETTING: Inpatient university-affiliated rehabilitation hospital. PATIENTS: 812 urban geriatric rehabilitation patients divided into four groups based on decade of life. MAIN OUTCOME MEASURES: Index of comorbid disease, principal diagnoses, Functional Independence Measure, Mattis Dementia Rating Scale, Geriatric Depression Scale, CAGE alcohol questionnaire, and residential status at admittance and discharge. RESULTS: Although there were no significant demographic differences between groups (apart from age), there were differences in functional outcome suggesting that the younger old (60s and 70s) and the older old (80s and 90+) patients may represent two different rehabilitation groups. CONCLUSIONS: The younger old patients showed significantly higher alcohol abuse and comorbid physical disease, while the older-old patients demonstrated significantly poorer cognitive skills and more dependent social status on discharge from the rehabilitation facility. Despite the younger group's physical problems and alcohol use, they demonstrated better physical recovery. Implications for working with these two groups of urban geriatric patients in a rehabilitation setting are discussed.

Soil and plant water relations in a crested wheatgrass pasture: response to spring grazing by cattle.

Few field studies have attempted to relate effects of actual livestock grazing on soil and plant water status. The present study was initiated to determine the effects of periodic defoliations by cattle during spring on soil moisture and plant water status in a crested wheatgrass (Agropyron cristatum (L.) Gaertn. and A. desertorum (Fisch. ex Link) Schult.) pasture in central Utah. Soil moisture in the top 130 cm of the soil profile was depleted more rapidly in ungrazed plots than in grazed plots during spring and early summer. Soil moisture depletion was more rapid in grazed plots in one paddock after 1 July due to differential regrowth, but there was no difference in soil water depletion between plots in another paddock during the same period. This difference in soil water depletion between paddocks was related to a difference in date of grazing. Although more water had been extracted from the 60 cm to 130 cm depths in ungrazed plots by late September, cumulative soil moisture depletion over the entire 193 cm profile was similar in grazed and ungrazed plots. Prior to 1 July, grazing had no effect on predawn leaf water potentials as estimated by a pressure chamber technique; however, after 1 July, predawn leaf water potentials were lower for ungrazed plants. Midday leaf water potentials were lower for grazed plants before 1 July, but did not differ between grazed and ungrazed plants after 1 July. A 4- to 8-day difference in date of defoliation did not affect either predawn or midday leaf water potentials. The observed differences in water use patterns during spring and early-summer may be important in influencing growth and competitive interactions in crested wheatgrass communities that are subject to grazing by domestic livestock.

A method for 13C enrichment of phospholipid acyl chains using Tetrahymena.

A method has been devised for obtaining highly 13C enriched (20-25%) phospholipids and membranes from the ciliate Tetrahymena, the enrichment occurring in the acyl chains. This method provides both phosphatidylcholine and phosphatidylethanolamine with enriched chains. The central feature of the method is the monoaxenic growth of Tetrahymena on an E. coli mutant which has a high incorporation of exogenous acetate into fatty acid chains. The 13C NMR spectra of the phospholipids are sufficiently enriched to permit NMR relaxation studies.