Climate change and the permafrost carbon feedback.

Large quantities of organic carbon are stored in frozen soils (permafrost) within Arctic and sub-Arctic regions. A warming climate can induce environmental changes that accelerate the microbial breakdown of organic carbon and the release of the greenhouse gases carbon dioxide and methane. This feedback can accelerate climate change, but the magnitude and timing of greenhouse gas emission from these regions and their impact on climate change remain uncertain. Here we find that current evidence suggests a gradual and prolonged release of greenhouse gas emissions in a warming climate and present a research strategy with which to target poorly understood aspects of permafrost carbon dynamics.

Verification of land-atmosphere coupling in forecast models, reanalyses and land surface models using flux site observations.

We confront four model systems in three configurations (LSM, LSM+GCM, and reanalysis) with global flux tower observations to validate states, surface fluxes, and coupling indices between land and atmosphere. Models clearly under-represent the feedback of surface fluxes on boundary layer properties (the atmospheric leg of land-atmosphere coupling), and may over-represent the connection between soil moisture and surface fluxes (the terrestrial leg). Models generally under-represent spatial and temporal variability relative to observations, which is at least partially an artifact of the differences in spatial scale between model grid boxes and flux tower footprints. All models bias high in near-surface humidity and downward shortwave radiation, struggle to represent precipitation accurately, and show serious problems in reproducing surface albedos. These errors create challenges for models to partition surface energy properly and errors are traceable through the surface energy and water cycles. The spatial distribution of the amplitude and phase of annual cycles (first harmonic) are generally well reproduced, but the biases in means tend to reflect in these amplitudes. Interannual variability is also a challenge for models to reproduce. Our analysis illuminates targets for coupled land-atmosphere model development, as well as the value of long-term globally-distributed observational monitoring.

A comparison of organized and traditional health care: implications for health promotion and prospective medicine.

PURPOSE: To compare organized and traditional health care delivery systems and their ability to meet several major challenges facing health care in the next 25 years. APPROACH: Analysis of traditional and organized health care systems based on a career spent in organized health care systems. CONCLUSIONS: The traditional health care system based on independent autonomous physicians is not able to meet the challenges of current healthcare. Stronger integration and coordination, i.e., organized health care delivery systems are required.

A simplified, data-constrained approach to estimate the permafrost carbon-climate feedback.

We present an approach to estimate the feedback from large-scale thawing of permafrost soils using a simplified, data-constrained model that combines three elements: soil carbon (C) maps and profiles to identify the distribution and type of C in permafrost soils; incubation experiments to quantify the rates of C lost after thaw; and models of soil thermal dynamics in response to climate warming. We call the approach the Permafrost Carbon Network Incubation-Panarctic Thermal scaling approach (PInc-PanTher). The approach assumes that C stocks do not decompose at all when frozen, but once thawed follow set decomposition trajectories as a function of soil temperature. The trajectories are determined according to a three-pool decomposition model fitted to incubation data using parameters specific to soil horizon types. We calculate litterfall C inputs required to maintain steady-state C balance for the current climate, and hold those inputs constant. Soil temperatures are taken from the soil thermal modules of ecosystem model simulations forced by a common set of future climate change anomalies under two warming scenarios over the period 2010 to 2100. Under a medium warming scenario (RCP4.5), the approach projects permafrost soil C losses of 12.2-33.4 Pg C; under a high warming scenario (RCP8.5), the approach projects C losses of 27.9-112.6 Pg C. Projected C losses are roughly linearly proportional to global temperature changes across the two scenarios. These results indicate a global sensitivity of frozen soil C to climate change (γ sensitivity) of -14 to -19 Pg C °C(-1) on a 100 year time scale. For CH4 emissions, our approach assumes a fixed saturated area and that increases in CH4 emissions are related to increased heterotrophic respiration in anoxic soil, yielding CH4 emission increases of 7% and 35% for the RCP4.5 and RCP8.5 scenarios, respectively, which add an additional greenhouse gas forcing of approximately 10-18%. The simplified approach presented here neglects many important processes that may amplify or mitigate C release from permafrost soils, but serves as a data-constrained estimate on the forced, large-scale permafrost C response to warming.

Hormone levels in the reproductive system of normospermic men and patients with oligospermia and varicocele.

The endocrine milieu on which spermatogenesis and sperm maturation mainly depend was evaluated quantitatively with simultaneous measurements of FSH, LH, PRL, testosterone, estrone, estradiol (E2), and sex hormone-binding globulin concentrations in spermatic venous plasma, antecubital plasma, seminal fluid, and wash fluid from vas deferens in 16 normospermic men and 24 oligospermic patients. Anesthesia and surgical stress caused a rise of only PRL and E2 (P less than 0.001-0.01). Mean FSH, LH, and PRL levels were comparable in antecubital and spermatic venous plasma, and antecubital values were higher in oligospermic patients for FSH and LH (P less than 0.05-0.001). Mean (+/- SD) T levels were similar for normospermic and oligospermic men in spermatic venous plasma (473 +/- 75 and 439 +/- 270 ng/ml), in antecubital plasma (6.5 +/- 1.3 and 6.6 +/- 1.8), and in seminal fluid (0.3 +/- 0.1 for both). Minute quantities of testosterone were detected in pooled wash fluid (0.08 ng). For E2, similar concentration gradients from high to low levels were found in normospermic and oligospermic men (spermatic venous plasma = 926 +/- 205 pg/ml and 1090 +/- 262; antecubital plasma = 31.0 +/- 12.0 and 28.4 +/- 1.9; seminal fluid = 14.3 +/- 2.3 and 12.0 + 2.8). Estrone was also high in spermatic venous and low in antecubital plasma but higher in seminal fluid than in antecubital plasma. Sex hormone-binding globulin levels were slightly though not significantly lower in spermatic venous (23 +/- 10 nmol/liter) than in antecubital plasma (28 +/- 6), but not measurable in seminal fluid. These results define important aspects of the endocrine milieu prevailing in the male reproductive tract and demonstrate a change of the relative activity of androgens and estrogens from the testis to the seminal fluid.

Fluorescent staining of kappa opioid receptors using naltrexamine derivatives and phycoerythrin.

An immunofluorescent technique that is more sensitive than radioligand binding was developed in order to detect opioid receptors expressed on leukocytes. The current study was designed to optimize the method for fluorescently labeling kappa opioid receptors. For these experiments, the opioid antagonist naltrexamine was conjugated to either fluorescein (FITC-NTXamine) or biotin (biotin-NTXamine). One-step, two-step, and three-step protocols were compared to determine which procedure resulted in optimal staining of the kappa opioid receptor expressed on intact, unfixed R1E/TL8x.1.OUAr.1(R1EGO) cells, a thymoma known to express kappa opioid receptors. The one-step method involved incubating cells with FITC-NTXamine, and the fluorescein intensity was measured by flow cytometry. In the two-step method, cells were incubated with biotin-NTXamine, followed by extravidin-conjugated phycoerythrin, and the phycoerythrin fluorescence was measured. Finally, in the three-step protocol, cells were incubated with FITC-NTXamine, followed by biotin-conjugated anti-fluorescein IgG, then extravidin-phycoerythrin. The one-step protocol stained the cells, but the signal was not diminished in the presence of opioid competitors. The two-step approach did not stain cells significantly above background levels. Only the three-step approach yielded staining that was displaced by the kappa-selective antagonist nor-binaltorphimine. Thus, the addition of a secondary biotinylated antibody, resulting in the amplification of binding, which was detected using phycoerythrin as a fluorophore, was required to detect low levels of opioid receptor expression on leukocytes.

Kappa opioid binding sites on the R1.1 murine lymphoma cell line: sensitivity to cations and guanine nucleotides.

The present study describes the characterization of an opioid binding site on membranes prepared from the R1.1 cell line, a murine thymoma. Specific (-)[3H]bremazocine binding was saturable, stereoselective, and limited to a single high affinity binding site with a Kd value of 15.2 +/- 1.6 pM and a Bmax value of 54.8 +/- 6.0 fmol/mg of protein. The kappa-selective alkaloids and dynorphin peptides inhibited (-)[3H]bremazocine binding with Ki values of less than 1 nM, in contrast to mu- and delta-selective ligands. The high affinity of this site for alpha-neo-endorphin and U50,488 suggests that this kappa opioid binding site resembles the kappa 1b subtype. NaCl, as well as other mono- and divalent cations, inhibited (-)[3H]bremazocine binding. In the presence of NaCl, the nucleotides GTP, GDP, and the nonhydrolyzable analog guanylyl-5'-imidodiphosphate (Gpp(NH)p) also decreased (-)[3H]bremazocine binding, suggesting that this kappa opioid binding site is coupled to a G-protein. In summary, R1.1 cells possess a single high affinity kappa opioid receptor that shares many properties with brain kappa 1b opioid receptors.

Kappa opioid receptors expressed on three related thymoma cell lines. Differences in receptor-effector coupling.

The mouse thymoma R1.1 cell line was shown previously to express a single high-affinity kappa 1 opioid receptor that is negatively coupled through a pertussis toxin-sensitive G-protein to adenylyl cyclase. This study compared opioid receptor binding and inhibition of adenylyl cyclase activity in three unique derivatives of the R1.1 cell line. Membranes from the R1.G1 and R1E/TL8x.1.G1.OUAr.1 (R1EGO) cell lines bound both [3H]U69,593 and [3H](-)-bremazocine with similar affinities compared with R1.1 membranes, whereas membranes from the R1E/TL8x.1 (R1E) cell line did not possess any opioid binding sites, detected by radioreceptor binding. The Bmax values for [3H]U69,593 and [3H]-(-)-bremazocine binding to R1.G1 and R1EGO cell membranes were, respectively, 3- and 6-fold greater than those obtained with the parent R1.1 cell line. GTP and its nonhydrolyzable analog, Gpp(NH)p, inhibited [3H]U69,593 binding to all three cell lines. Stimulation of low-Km GTPase activity by the kappa-selective agonist (-)U50,488 was greatest in R1.G1 membranes, followed by R1EGO and R1.1. The maximal inhibition of forskolin-stimulated adenylyl cyclase activity by (-)U50,488 was 66 +/- 2% in R1.G1 and 49 +/- 2% in R1EGO, compared with 37 +/- 1% in R1.1 membranes. Whereas maximal inhibition of adenylyl cyclase activity did not correlate with receptor number among cell lines, the inhibition of cyclic AMP production did correlate with stimulation of low-Km GTPase activity. The R1.1 cell line and its derivatives, R1.G1 and R1EGO, express a similar type of kappa opioid receptor, which exhibits differences in coupling to G-proteins and to adenylyl cyclase among cell lines. These cell lines provide an excellent model system for studying the regulation of opioid receptor-adenylyl cyclase coupling efficiency.

kappa-Opioid binding sites on a murine lymphoma cell line.

As a first step in determining whether any subset of lymphocytes expresses opioid receptors, membranes prepared from mouse lymphoma cell lines were screened for [3H]naloxone binding sites. Membranes from the R1.1 cell line specifically bound [3H]naloxone. The Hill coefficient for [3H]naloxone binding was 0.93 +/- 0.18, and nonlinear regression analysis indicated that a one-site model was the best fit of the [3H[naloxone saturation binding data. Low concentrations of kappa-selective opioids, but neither mu nor delta opioids, inhibited [3H]naloxone binding. Saturation binding studies with the kappa-selective compound [3H]U69,593 revealed a single binding site with a KD value of 0.204 +/- 0.039 nM and a Bmax value of 31.7 +/- 3.1 fmol/mg of membrane protein. The Hill coefficient for [3H]U69,593 binding was 1.03 +/- 0.11, indicative of a single site. Time courses for the association and dissociation of [3H]U69,593 binding at 25 degrees C exhibited properties consistent with a single class of binding sites. Low concentrations of kappa-selective opioids, including dynorphin peptides, inhibited [3H]U69,593 binding, while high concentrations of mu opioids were needed to inhibit binding, and the delta-selective ligands were ineffective at concentrations up to 10 microM. Stereoselectivity of the binding site was demonstrated by the finding that the Ki value for (-)-pentazocine in inhibiting [3H]U69,593 binding was 25 times less than for the (+)-isomer. Based on its high affinity for U69,593, alpha-neo-endorphin, and dynorphin B, the kappa opioid binding site on R1.1 cell membranes belongs to the kappa 1b subtype. As observed with brain kappa opioid binding sites, sodium inhibited [3H]U69,593 binding to R1.1 cell membranes in a concentration-dependent manner. These data demonstrate that the murine lymphoma cell line R1.1 expresses kappa opioid binding sites that are very similar to brain kappa opioid binding sites.

Cutaneous lesions in hairy-cell leukemia. Case report and review of the literature.

A patient is described in whom cutaneous lesions were the initial manifestation of hairy-cell leukemia. Touch preparations made immediately on removal of a 3-mm punch biopsy specimen of the cutaneous lesions revealed acid-phosphatase positive, tartrate-resistant staining in the leukemic cells, and helped to establish the diagnosis. Specific eruptions occur in approximately 7% of patients with hairy-cell leukemia, appearing grossly as disseminated, erythematous maculopapules, with a perivascular mononuclear leukemic cell infiltrate seen microscopically. A review of the English literature indicates that cutaneous manifestations are not generally recognized as a diagnostic source in individuals with hairy-cell leukemia, and biopsy is seldom undertaken.

Changes in vestibulo-ocular reflex (VOR) anticipate changes in vergence angle in monkey.

The axis of head rotation is usually different from the axis of eye rotation. Geometrical considerations show that the eyes translate with respect to visual targets located near the head. In order to accurately stabilize retinal images against this translation, the vestibulo-ocular reflex (VOR) must be modulated inversely with the target's distance. The neural correlate of viewing distance used to modulate the VOR is not known. Since vergence angle is related inversely to viewing distance, an efference copy of instantaneous vergence angle or proprioceptive afferent information from extraocular muscles could be used to adjust the VOR. To examine this hypothesis, we compared the time-course of changes in the VOR with the time-course of changes in vergence angle. The VOR was induced by briefly rotating monkeys about a vertical axis at different times during the execution of vergence eye movements. We found that the amplitude of the VOR changed systematically during the course of a vergence eye movement. On average, the changes in the amplitude of vestibular induced eye movements anticipated changes in vergence angle by 50 msec, but in some instances, up to 200 msec of anticipation was observed. These data suggest that a central command signal rather than an afferent or efferent copy of vergence eye position was used to modulate the VOR.

Suicide rates in psychiatric in-patients: an application of record linkage to mental health research.

OBJECTIVE: To study trends in the rate of suicide in psychiatric patients in Western Australia. To examine the associations of suicide with demographic and clinical factors. METHODS: A population-based cohort of 52,010 individuals whose first psychiatric admission occurred in 1980-95 was identified from the Health Services Research Linked Database. There were 471 deaths by suicide by 31 December 1995. Age standardised suicide rates per 1,000 person-years at risk were calculated. Suicide rates in the first year after a patient's first admission were also examined and a proportional hazards regression analysis was performed to examine risk factors for suicide. RESULTS: Male psychiatric patients were 3.4 times more likely to commit suicide than female patients (95% CI 2.76-4.24). Younger patients were at higher risk than older patients, and patients with extended periods of in-patient treatment were at more than double the risk of short-stay patients. Over the 16-year period, the rate of suicide in the first year after first psychiatric admission was found to increase by 3.4% a year (95% CI -0.7-7.6%). CONCLUSIONS: The findings confirm that psychiatric patients are at high risk of suicide. Patient outcomes in terms of risk of suicide after hospital discharge have deteriorated. IMPLICATIONS: Improvements are needed in the provision of community support to high risk psychiatric patients. Further work should be done to identify patients at highest risk of suicide.

Gastrointestinal trauma.

The incidence of gastrointestinal trauma is low in comparison with solid organ injury to the abdomen. The most commonly injured organs are the small bowel and colon. Knowledge of the mechanism of injury alerts the nurse to areas of potential injury and guides the clinical examination. Because of the delayed presentation of these injuries, the nurse must have a high degree of suspicion for the patient who presents with the following clinical findings: bruising of the abdomen, abdominal tenderness or guarding, leukocytosis and elevated amylase and lipase, absent or decreased bowel sounds, and abdominal distention. Morbidity and mortality are directly related to the failure to treat the injuries early and the number of associated injuries. Monitoring of the hemodynamic, respiratory, and metabolic status, along with fluid and electrolyte balance, are key in the management of patients. Surveillance for signs of infection is mandatory for preventing sepsis in these types of injuries. Maintenance of skin integrity is a major concern and requires vigilant nursing care and, in some instances, innovative ways to manage the drainage from wounds and drains. Continuous monitoring and surveillance of the patient with trauma to the gastrointestinal tract will alert the nurse to the injury and prevent complications. These include hemorrhage, abscess, fistula, peritonitis, pancreatitis, esophageal stricture, and wound problems.

Role of verbal representations in testing recognition of naturalistic sounds.

This paper reports two experiments concerned with verbal representation in the test stage of recognition memory for naturalistic sounds. In Study I 10 subjects produced verbal description to 50 sounds and after a 7-day delay 5 subjects reviewed self-produced verbal descriptions while 5 did not prior to testing for recognition. Review of descriptions increased recognition to 94.4% compared to 88.5% for those with no review. In Study II 16 subjects produced verbal descripitions to 50 naturalistic sounds. After a 7-day delay all subjects reviewed descriptionss of one-half of the items which were "targets" and 8 subjects reviewed description of 25 "non-targeted" items. The latter condition produced interference, observed as a significant decrement in recognition from 90.3% to 86.5%.

Cross-modal utilization of information: recognition memory for environmental stimuli.

In a study of cross-modal recognition memory for vision and audition photographs were matched for meaningful content with naturalistic sounds. Fifteen subjects inspected pictures and were tested with sounds and for 15 other the procedure was reversed. The two cross-modal groups were further divided into subgroups of 5 to test at one of three delays: immediate, 2 days, or 7 days. Accuracies for recognition of vision-audition for the respective retention intervals were 88.0%, 81.8%, and 75.4% and for audition-vision 87.9%, 85.1%, and 76.7%. Delay interval significantly affected cross-modal recognition. There was no interaction. Vision-audition recognition accuracy did not differ from audition-vision. The cross-modal recognition for both was high. Neither differed from a comparable intra-modal recognition memory for naturalistic sounds (Lawrence, 1974).

Associating Embedded Figures Test Performance with extreme hysteria and psychasthenia MMPI scores in a psychiatric population.

21 female subjects from a psychiatric population scoring high on one of two MMPI scales, Hysteria or Psychasthenia, were given Jackson's (1956) shortened version of the Embedded Figures Test. Hysteria correlates positively and significantly .71 with time spent in detecting embedded geometric figures. Obsessive-compulsiveness and Embedded Figures Test performance time are negatively correlated -.63. The average times were 102.5 sec. for hysteria subjects and 62.6 sec. for psychasthenia subjects. Chi-squared establishes the significant association of MMPI measurements for hysteria and obsessive-compulsiveness with field-dependence and field-independence, respectively.

Comparison of accuracy in auditory and tactile recognition memory for environmental stimuli.

Accuracy rates for auditory and tactile recognition of naturalistic stimuli over a 7-day period are compared. 40 subjects listened to 50, 107, or 194 naturalistic sounds and were tested immediately or after delays of 2 or 7 days. 30 other subjects handled but did not visually inspect 150 common objects and were tested over the same three delay intervals. Recognition accuracy for sounds was 87.5%, 82.5%, and 80.4% while common objects were recognized at 96.0%, 93.8%, and 88.5% rates of accuracy. Tactile recognition memory was superior to auditory recognition memory. The recognition accuracies of both modalities were affected by the delay interval. The number of items inspected had no effect on the recognition memory for sounds. Following a delay of 1 wk., the accuracy of recognition relative to the original level of function was 92% for both modalities.

Report on blind subjects' tactile and auditory recognition for environmental stimuli.

In two related experiments on recognition-on touch and audition-accuracy rates were obtained from congenitally blind subjects and compared with those for normally sighted subjects. In Exp. 1, 5 blind subjects inspected, i.e., handled, 150 common objects and were tested after a delay of 7 days. In Exp. 2, 9 blind subjects listened to 194 naturalistic sounds and were also tested after a 7-day delay. Accuracy of tactile recognition for the blind was 89.4% while it was 87.9% for the normally sighted. Sound recognition by blind subjects was 76.6% and for the normally sighted it was 78.4%. Neither difference was statistically significant.

Influence of active encoding on tactile recognition memory for common objects.

Active tactile recognition memory for common objects is compared with passive touch. The recognition memory test occure after a delay between inspection and test of seven days. Three groups of five each have the following conditions and results: Group I manipulated objects at both inspection and test to obtain a recognition rate of 87.9%; Group II manipulated objects at inspection but not at test, i.e., passive touch, to produce a recognition rate of 80.7%; Group III manipulated objects at test but not at inspection to perform at a 72.5% accuracy rate. Object manipulation had a significant effect and the group means were all significantly different (p less than or equal to .05), with the largest performance decrement due to passive touch at encoding. Generally, the findings implicated the importance of object identity in tactile recognition memory which, in turn, is supportive of the depth-of-processing approach to memory.

Governance challenges for managed care organizations. Interview by Ann C. Bartling.

When Healthcare Executive asked managed care organization CEOs and board chairs to identify governance challenges, they found the question so easy that it was difficult to limit their responses. while all the healthcare leaders interviewed pointed to the need to--and challenge of--staying ahead of the changes affecting the healthcare field, many identified challenges that were more specific to their organizations, markets, or patient population. Some also pointed out that while their challenges may be shared by hospitals and other provider organizations, there were aspects of each that were particularly relevant to managed care organizations, which often offer a variety of products in a number of different of markets.