Type A achievement striving and failure to achieve personal goals

The purpose of the present study was to examine relations involving the Type A behavior pattern, goal-setting behavior, and goal achievement. Type A and B subjects completed two sequential general information tests. On each test, subjects were required to establish a performance goal prior to the test, and after completing the test, subjects were given feedback on their actual performance. On both tests, results confirmed that Type A's, compared to Type B's, set significantly higher performance goals, performed no differently, showed significantly larger discrepancies between performance and goals, were significantly less likely to achieve their performance goal. Furthermore, it was found that Type A's set goals on test 2 that exceeded their test 1 performance to a greater extent than Type B's, but only among subjects who failed to achieve their test 1 goals. No differences were found between Type A's and B's on goal-setting behavior following a success in goal achievement on test 1. Results of the experiment suggest that Type A achievement striving represents a breakdown in achievement-related self-regulation, which may have negative psychological consequences associated with failure to achieve personal goals.     

Receptor occupancy of nonpeptide corticotropin-releasing factor 1 antagonist DMP696: correlation with drug exposure and anxiolytic efficacy

4-(1,3-Dimethoxyprop-2-ylamine)-2,7-dimethyl-8-(2,4-dichlorophenyl)-pyrazolo[1,5-a]-1,3,5-triazine (DMP696) is a highly selective and potent, nonpeptide corticotropin-releasing factor 1 (CRF(1)) antagonist. In this study, we measured in vivo CRF(1) receptor occupancy of DMP696 by using ex vivo ligand binding and quantitative autoradiography and explored the relationship of receptor occupancy with plasma and brain exposure and behavioral efficacy. In vitro affinity (IC(50)) of DMP696 to brain CRF(1) receptors measured using the brain section binding autoradiography in this study is similar to that assessed using homogenized cell membrane assays previously. The ex vivo binding assay was validated by demonstrating that potential underestimation of receptor occupancy with this procedure could be minimized by identifying an appropriate in vitro incubation time (40 min) based upon the dissociation kinetics of DMP696. Orally administrated DMP696 dose dependently occupied CRF(1) receptors in the brain, with ~60% occupancy at 3 mg/kg. In the defensive withdrawal test of anxiety, this dose of DMP696 produced approximately 50% reduction in the exit latency. The time course of plasma and brain drug levels paralleled that of receptor occupancy, with peak exposure at 90 min after dosing. The plasma-free concentration of DMP696 corresponding to 50% CRF(1) receptor occupancy (in vivo IC(50), 1.22 nM) was similar to the in vitro IC(50) (~1.0 nM). Brain concentrations of DMP696 were over 150-fold higher than the plasma-free levels. In conclusion, doses of DMP696 occupying over 50% brain CRF(1) receptors are consistent with doses producing anxiolytic efficacy in the defense withdrawal test of anxiety, and the IC(50) value estimated in vivo based on plasma-free drug concentrations is consistent with the in vitro IC(50) value.     

A two-millimetre free margin from invasive tumour minimises residual disease in breast-conserving surgery

Aims: In breast‐conserving surgery, the width of free margin around a tumour to ensure adequate excision is controversial. The aim of this study was first to evaluate the frequency of residual disease in wider excision specimens in patients who undergo further surgery because of close margins of < 5 mm. Secondly, the ability of demographic and tumour‐related factors to predict the close margins was appraised. Patients and methods: Three‐hundred‐and‐three patients were included in the study. Patients undergoing wider excision were assessed for the presence of residual disease, and this was tested for association with the width of the initial free margin. Various factors were studied for association with close or involved margins by univariate analysis. Results: Fifty‐three per cent of patients were eligible for re‐excision based on the need for a 5‐mm clearance. With a free margin of 2 mm or more from invasive tumour, the probability of finding residual disease was 2.4%. The probability of residual disease was higher for ductal carcinoma in situ (DCIS) and did not decline with increasing the free margin width. Tumour size, lobular cancer type, vascular invasion and nodal involvement were associated with close margins. Conclusions: We suggest that a free margin of 2 mm from invasive tumour is adequate to minimise residual disease, whereas the equivalent free margin for DCIS remains unclear. Patients with large tumours and lobular cancer type should be counselled at the time of first surgery concerning the higher risk of further excision and mastectomy.     

A new noninvasive method to determine central venous pressure

Knowledge of central venous pressure (CVP) is considered valuable in the assessment and treatment of various states of critical illness and injury. OBJECTIVES: We tested a noninvasive means of determining CVP (NICVP), by monitoring forearm volume changes in response to externally applied circumferential pressure to the upper arm veins. METHODS: Sixteen patients who were undergoing CVP monitoring as a part of their care had NICVP determined and compared with CVP. Volume changes were measured in the forearm with mercury-in-silastic strain gauge plethysmography. A pressure cuff is placed in the upper extremity. The cuff is inflated over 5s to a pressure above CVP but below diastolic arterial pressure (40 mmHg). This allows blood into the forearm but prevents venous return. After 45-60 s the cuff is rapidly deflated. NICVP was determined as the cuff pressure noted at the maximum derivative of the forearm volume decrease during deflation. NICVP was then compared to invasively measured CVP taken during the same period. RESULTS: A total of 48 trials (three per subject) were performed on 16 patients. The range of CVP recorded was 0-22 mmHg. The correlation between CVP and NICVP was 0.98 (95% CI: 0.95-0.98) (p<0.001). The bias between methods was 0.26 mmHg with the limits of agreement being 3.4 to -2.89 mmHg. When the average of three trials per patients was analysed the bias stayed at 0.26 mmHg but the limits of agreement improved to 2.54 and -2.03 mmHg. CONCLUSION: NICVP as determined in this study may be a clinically useful substitute for traditional CVP measurement and may offer a valid tool for early diagnosis and treatment of acute states in which knowledge of CVP would be helpful.     

Methods for studying the binding of aluminum by serum protein

We describe methods for studying the binding of Al by protein in serum: ultrafiltration, gel filtration, and immuno-affinity chromatography. For ultrafiltration we used an Amicon YM10 cellophane membrane with a nominal cutoff of 10 000 Da to separate ultrafiltrable and non-ultrafiltrable Al. For gel filtration we used Sephacryl S-300, and for immuno-affinity chromatography we used anti-transferrin coupled to CNBr-activated Sepharose to identify the Al-binding protein. For 30 normal subjects 54% of the total Al in serum was non-ultrafiltrable; for 30 patients with chronic renal failure being treated by hemodialysis 67% was non-ultrafiltrable. In both groups transferrin was identified as the major Al-binding protein in the serum. Results of gel-filtration studies should be interpreted with caution: some gel media adsorb "free" Al, which can be subsequently taken up by transferrin or desferrioxamine passing through the column. We find affinity chromatography to be a specific and reliable method, suitable for use in quantitative studies.     

A randomized trial of intermittent lorazepam versus propofol with daily interruption in mechanically ventilated patients

OBJECTIVE: To compare duration of mechanical ventilation for patients randomized to receive lorazepam by intermittent bolus administration vs. continuous infusions of propofol using protocols that include scheduled daily interruption of sedation. DESIGN: A randomized open-label trial enrolling patients from October 2001 to March 2004. SETTING: Medical intensive care units of two tertiary care medical centers. PATIENTS: Adult patients expected to require mechanical ventilation for >48 hrs and who required > or =10 mg of lorazepam or a continuous infusion of a sedative to achieve adequate sedation. INTERVENTIONS: Patients were randomized to receive lorazepam by intermittent bolus administration or propofol by continuous infusion to maintain a Ramsay score of 2-3. Sedation was interrupted on a daily basis for both groups. MEASUREMENTS AND MAIN RESULTS: The primary outcome was median ventilator days. Secondary outcomes included 28-day ventilator-free survival, intensive care unit and hospital length of stay, and hospital mortality. Median ventilator days were significantly lower in the daily interruption propofol group compared with the intermittent bolus lorazepam group (5.8 vs. 8.4, p = .04). The difference was largest for hospital survivors (4.4 vs. 9.0, p = .006). There was a trend toward greater ventilator-free survival for patients in the daily interruption propofol group (median 18.5 days for propofol vs. 10.2 for lorazepam, p = .06). Hospital mortality was not different. CONCLUSIONS: For medical patients requiring >48 hrs of mechanical ventilation, sedation with propofol results in significantly fewer ventilator days compared with intermittent lorazepam when sedatives are interrupted daily.     

Motor Vehicle Crash Fatalities among Hispanics in Rural North Carolina

OBJECTIVES: Deaths from motor vehicle crashes (MVCs) have decreased significantly over the past three decades. Unfortunately, few data have been collected regarding death rates for MVCs in minority populations. The purpose of this study was to compare the death rate of whites versus Hispanics for MVCs in a rural environment. METHODS: This study examined one rural county in North Carolina from January 1, 1999, to December 31, 1999. A retrospective cohort study was performed using the North Carolina State Highway Patrol computerized database of MVCs. Data regarding the total number of MVCs, fatalities, alcohol-related deaths, seatbelt usage, and cause of the collision were analyzed for both whites and Hispanics. Census information regarding population in this region also was obtained from the U.S. Bureau of Census. Data were analyzed using a chi-square test, with an alpha value of 0.05 used to establish statistical significance. RESULTS: During the study period, whites were involved in 2,689 MVCs, compared with 158 MVCs for Hispanics. Whites were involved in ten fatal MVCs, compared with seven fatal MVCs involving Hispanics. The percent of fatal MVCs for whites was 0.3%, or 10 deaths per 2,689 MVCs. In contrast, the percent of fatal MVCs for Hispanics was 4.4%, or 7 deaths per 158 MVCs; odds ratio (OR) = 12.4, 95% CI = 4.7 to 33.1. The 2000 Census Report for Pitt County noted a white population of 81,613 and a Hispanic population of 4,216. Based on these population data, the death rate for MVCs per 100,000 population was 12.3 for whites versus 166.0 for Hispanics, OR = 13.6, 95% CI = 5.2 to 35.6. Although the cause for this disparity was not determined, previous studies suggest that alcohol and decreased seatbelt usage are contributing factors. CONCLUSIONS: In this study, the death rates among Hispanics for rural MVCs were significantly higher than for whites. The causes of this disparity are not clear but are important to define. Only by understanding this disparity can we begin to develop appropriate interventions that may prevent these deaths.     

cIAP2 Is an Independent Signaling and Survival Factor during Mammary Lactational Involution and Tumorigenesis

Cellular inhibitor of apoptosis proteins-1 and -2 (cIAP1/2) are integral to regulation of apoptosis and signaling by the tumor necrosis factor (TNF) and related family of receptors. The expression of cIAP2 in tissues is typically low and considered functionally redundant with cIAP1, however cIAP2 can be activated by a variety of cellular stresses. Members of the TNFR family and their ligands have essential roles in mammary gland biology. We have found that cIAP2^?/? virgin mammary glands have reduced ductal branching and delayed lobuloalveogenesis in early pregnancy. Post-lactational involution involves two phases where the first phase is reversible and is mediated, in part, by TNFR family ligands. In cIAP2?/? mice mammary glands appeared engorged at mid-lactation accompanied by enhanced autophagic flux and decreased cIAP1 protein expression. Severely stretched myoepithelium was associated with BIM-EL expression and other indicators of anoikis. Within 24 h after forced or natural weaning, cIAP2^?/? glands had nearly completed involution. The TNF-related weak inducer of apoptosis (Tweak) which results in degradation of cIAP1 through its receptor, Fn14, began to increase in late lactation and was significantly increased in cIAP2^?/? relative to WT mice by 12 h post weaning accompanied by decreased cIAP1 protein expression. Carcinogen/progesterone-induced mammary tumorigenesis was significantly delayed in cIAP2^?/? mice and tumors contained high numbers of apoptotic cells. We conclude that cIAP2 has a critical role in the mammary gland wherein it prevents rapid involution induced by milk stasis-induced stress associated with Tweak activation and contributes to the survival of mammary tumor cells.     

Anabolic Therapy for the Treatment of Osteoporosis in Childhood

Purpose of Review

Numerous forms of osteoporosis in childhood are characterized by low bone turnover (for example, osteoporosis due to neuromuscular disorders and glucocorticoid exposure). Anti-resorptive therapy, traditionally used to treat osteoporosis in the young, is associated with further reductions in bone turnover, raising concerns about the long-term safety and efficacy of such therapy. These observations have led to increasing interest in the role of anabolic therapy to treat pediatric osteoporosis.

Recent Findings

While growth hormone and androgens appears to be relatively weak anabolic modulators of bone mass, emerging therapies targeting bone formation pathways (anti-transforming growth factor beta antibody and anti-sclerostin antibody) hold considerable promise. Teriparatide remains an attractive option that merits formal study for patients post-epiphyseal fusion, although it must be considered that adult studies have shown its effect is blunted when administered following bisphosphonate therapy. Mechanical stimulation of bone through whole body vibration therapy appears to be much less effective than bisphosphonate therapy for treating osteoporosis in children.

Summary

New anabolic therapies which target important pathways in skeletal metabolism merit further study in children, including their effects on fracture risk reduction and after treatment discontinuation.

     

Health Insurance Status and Psychological Distress among US Adults Aged 18–64 Years

The purpose of this research was to examine the relationship between psychological distress and aspects of health insurance status, including lack of coverage, types of coverage and disruption in coverage, among US adults. Data from the 2001–2010 National Health Interview Survey were used to conduct analyses representative of the US adult population aged 18–64 years. Multivariate analyses regressed psychological distress on health insurance status while controlling for covariates. Adults with private or no health insurance coverage had lower levels of psychological distress than those with public/other coverage. Adults who recently (≤1 year) experienced a change in health insurance status had higher levels of distress than those who had not recently experienced a change. An interaction effect indicated that the relationship between recent change in health insurance status and distress was not dependent on whether an adult had private versus public/other coverage. However, for adults who had not experienced a change in status in the past year, the average absolute level of distress is higher among those with no coverage versus private coverage. Although significant relationships between psychological distress and health insurance status were identified, their strength was modest, with other demographic and health condition covariates also being potential sources of distress. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.