Dopamine promotes cognitive effort by biasing the benefits versus costs of cognitive work.

Stimulants such as methylphenidate are increasingly used for cognitive enhancement but precise mechanisms are unknown. We found that methylphenidate boosts willingness to expend cognitive effort by altering the benefit-to-cost ratio of cognitive work. Willingness to expend effort was greater for participants with higher striatal dopamine synthesis capacity, whereas methylphenidate and sulpiride, a selective D2 receptor antagonist, increased cognitive motivation more for participants with lower synthesis capacity. A sequential sampling model informed by momentary gaze revealed that decisions to expend effort are related to amplification of benefit-versus-cost information attended early in the decision process, whereas the effect of benefits is strengthened with higher synthesis capacity and by methylphenidate. These findings demonstrate that methylphenidate boosts the perceived benefits versus costs of cognitive effort by modulating striatal dopamine signaling.

Abnormal cognitive effort allocation and its association with amotivation in first-episode psychosis.

BACKGROUND: Abnormal effort-based decision-making represents a potential mechanism underlying motivational deficits (amotivation) in psychotic disorders. Previous research identified effort allocation impairment in chronic schizophrenia and focused mostly on physical effort modality. No study has investigated cognitive effort allocation in first-episode psychosis (FEP). METHOD: Cognitive effort allocation was examined in 40 FEP patients and 44 demographically-matched healthy controls, using Cognitive Effort-Discounting (COGED) paradigm which quantified participants' willingness to expend cognitive effort in terms of explicit, continuous discounting of monetary rewards based on parametrically-varied cognitive demands (levels N of N-back task). Relationship between reward-discounting and amotivation was investigated. Group differences in reward-magnitude and effort-cost sensitivity, and differential associations of these sensitivity indices with amotivation were explored. RESULTS: Patients displayed significantly greater reward-discounting than controls. In particular, such discounting was most pronounced in patients with high levels of amotivation even when N-back performance and reward base amount were taken into consideration. Moreover, patients exhibited reduced reward-benefit sensitivity and effort-cost sensitivity relative to controls, and that decreased sensitivity to reward-benefit but not effort-cost was correlated with diminished motivation. Reward-discounting and sensitivity indices were generally unrelated to other symptom dimensions, antipsychotic dose and cognitive deficits. CONCLUSION: This study provides the first evidence of cognitive effort-based decision-making impairment in FEP, and indicates that decreased effort expenditure is associated with amotivation. Our findings further suggest that abnormal effort allocation and amotivation might primarily be related to blunted reward valuation. Prospective research is required to clarify the utility of effort-based measures in predicting amotivation and functional outcome in FEP.

Canis Caveat (Beware of the Dog) - Septic Shock Due To Capnocytophaga Canimorsus Contracted From A Dog Bite

We describe the case of a 61-year-old immunocompetent male who developed septic shock and multiorgan failure due to Capnocytophaga canimorsus (C. canimorsus) bloodstream infection, sustained from a dog bite. Unusually, this patient developed acute liver failure and splenic infarction in addition to many of the better-known clinical sequelae of C. canimorsus infection.

Day or overnight transfusion in critically ill patients: does it matter?

BACKGROUND AND OBJECTIVES: The timing of blood administration in critically ill patients is first driven by patients' needs. This study aimed to define the epidemiology and significance of overnight transfusion in critically ill patients. MATERIALS AND METHODS: This is a post hoc analysis of a prospective multicentre observational study including 874 critically ill patients receiving red blood cells, platelets, fresh frozen plasma (FFP) or cryoprecipitate. Characteristics of patients receiving blood only during the day (8 am up until 8 pm) were compared to those receiving blood only overnight (8 pm up until 8 am). Characteristics of transfusion were compared, and factors independently associated with major bleeding were analysed. RESULTS: The 287 patients transfused during the day only had similar severity and mortality to the 258 receiving blood products overnight only. Although bleeding-related admission diagnoses were similar, major bleeding was the indication for transfusion in 12% of patients transfused in daytime only versus 30% of patients transfused at night only (P < 0·001). Similar total amount of blood products were transfused at day and night (2856 versus 2927); however, patients were more likely to receive FFP and cryoprecipitate at night compared with daytime. Overnight transfusion was independently associated with increased odds of major bleeding (odds ratio, 3·16, 95% confidence interval, 2·00-5·01). CONCLUSION: Transfusion occurs evenly across day and night in ICU; nonetheless, there are differences in type of blood products administered that reflect differences in indication. Critically ill patients were more likely to receive blood for major bleeding at night irrespective of admission diagnosis.

Effect of water velocity on hydroponic phytoremediation of metals.

The influence of flow velocity on the uptake of cadmium, copper, lead, and zinc by hydroponically grown soft stem bulrush (Scirpus validus) was investigated. The roots of the plants were exposed to a continually recycled, nutrient enriched, synthetic stormwater. Plants were divided into groups and the roots of each group exposed to different but constant water velocities. The metal concentrations in the roots and stems were compared after three weeks. Metal accumulation in roots was increased for water velocities between 1.3 and 4.0 cm s(-1). In a second experiment, the roots of all plants were exposed to a single velocity and the root and stem metal concentrations were determined as a function of time. Metal concentrations in the roots approached a constant value after three weeks. After this time, accumulation of metals depends upon root growth. The results suggest that long-term accumulation by the roots of hydroponic Scirpus validus can be increased by increasing water velocity, which implies that floating islands with movement will retain more metals from the water column.

Transfusion practice and guidelines in Australian and New Zealand intensive care units.

OBJECTIVE: To describe the relationship between clinical practice and national guidelines for the transfusion of red blood cells (RBCs), fresh frozen plasma (FFP), platelets, and cryoprecipitate in Australian and New Zealand intensive care units (ICUs). SETTING: Forty-seven ICUs over a 5-week period from August to September 2008. DESIGN: Prospective, observational, multicentre, cohort study. PATIENTS: A total of 874 patients receiving any type of blood transfusion. METHODS: All patients who were transfused at least one unit of any blood component were included. Patient-specific and blood-component specific data were gathered. Pre-transfusion haemoglobin, platelet count, international normalised ratio (INR), and fibrinogen levels were compared to national guidelines. RESULTS: Of all 874 patients, 757 received RBCs (86.6%), 231 (26.4%) received platelets, 340 (38.9%) received FFP, and 78 (8.9%) received cryoprecipitate. Bleeding was the reason for administration of RBCs in 46%, FFP in 55%, and platelets in 47% of transfusions. The mean (SD) pre-transfusion haemoglobin was 77.6 (9.5) g/l, while the geometric means (95% CI) for platelet count, INR, and fibrinogen were 67.0 (59.7-75.3) x 10(9)/l, 1.84 (1.76-1.93), and 1.4 (1.1-1.8) g/l, respectively. The proportions of transfusions not adherent to guidelines were 2% for RBC, but 53% for platelets, 29% for FFP, and 88% for cryoprecipitate (RBC vs. other transfusion p < 0.001 for all). CONCLUSIONS: Transfusion practice of RBCs in Australian and New Zealand ICUs is restrictive and is concordant with guidelines. However, the transfusion of other blood components is not.

The clinical significance of malunion of fractures of the neck and shaft of the little finger metacarpal.

The outcomes of 218 little finger metacarpal shaft and neck fractures that had been treated non-operatively, with no attempt at fracture reduction, were compared with those of 44 that had been treated operatively with fracture reduction and fixation (plates or K-wires). Outcome measures included the grip strength of the little finger and the DASH score. Fracture malunion was assessed by clinical measurement of little finger ray shortening and measurement of palmar angulation on the initial radiographs. The severity of palmar angular deformity did not affect the outcome of the 105 metacarpal neck or 113 metacarpal shaft fractures that had been treated non-operatively. There were no differences between the outcomes of the 18 metacarpal neck fractures treated operatively and the 105 treated non-operatively. The DASH score (P = 0.001) and aesthetic outcome (P = 0.013) were significantly better for the 113 metacarpal shaft fractures treated non-operatively than for the 26 treated operatively.

Multigene analysis suggests ecological speciation in the fungal pathogen Claviceps purpurea.

Claviceps purpurea is an important pathogen of grasses and source of novel chemical compounds. Three groups within this species (G1, G2 and G3) have been recognized based on habitat association, sclerotia and conidia morphology, as well as alkaloid production. These groups have further been supported by Random Amplification of Polymorphic DNA (RAPD) and amplified fragment length polymorphism (AFLP) markers, suggesting this species may be more accurately described as a species complex. However, all divergent ecotypes can coexist in sympatric populations with no obvious physical barriers to prevent gene flow. In this study, we used both phylogenetic and population genetic analyses to test for speciation within C. purpurea using DNA sequences from ITS, a RAS-like locus, and a portion of beta-tubulin. The G1 types are significantly divergent from the G2/G3 types based on each of the three loci and the combined dataset, whereas the G2/G3 types are more integrated with one another. Although the G2 and G3 lineages have not diverged as much as the G1 lineage based on DNA sequence data, the use of three DNA loci does reliably separate the G2 and G3 lineages. However, the population genetic analyses strongly suggest little to no gene flow occurring between the different ecotypes, and we argue that this process is driven by adaptations to ecological habitats; G1 isolates are associated with terrestrial grasses, G2 isolates are found in wet and shady environments, and G3 isolates are found in salt marsh habitats.

An evaluation of a clinical method to assess malunion of little finger metacarpal fractures.

This study assessed the reliability, responsiveness and validity of two clinical measurements for the assessment of malunion of little finger metacarpal neck and shaft fractures. Both compared the relative lengths of the ring and little fingers in the injured and contralateral hands. One measurement was taken with the metacarpophalangeal joints extended (straight-MCP), and the other with them flexed to 90 degrees (90-MCP). Ninety-five percent of the differences between the relative lengths of the ring and little fingers in the two hands of 50 normal subjects were less than 3mm and the 95% limits of agreement for repeat measurements (intra-observer reproducibility) was +/- 1 mm for both measurements. Both measurements were significantly altered in a group of 218 patients with a past history of a metacarpal shaft or neck fracture. Although both measurements correlated with the patient's assessment of the cosmetic result (p = 0.01), neither measurement correlated with the severity of palmar angulation of the fracture at presentation. It is concluded that these measurements are reliable and responsive, but their validity is uncertain.

The rapid exchange grip strength test and the detection of submaximal grip effort.

This study assessed the reliability of the rapid exchange grip test for detecting submaximal grip effort, particularly evaluating its performance with motivated subjects with genuine hand weakness secondary to pain. Fifty normal participants performing with maximum effort then feigning hand weakness and 50 patients recovering from carpal tunnel surgery were studied. The results showed that the dynamic measure of grip strength equaled or exceeded the static measure in 28% of maximally performing participants (72% specificity), 58% of the carpal tunnel decompression patients (42% specificity), and 74% of participants giving submaximal grip effort (74% sensitivity). Sensitivities and specificities for other criteria of a positive test were also determined. Our findings suggest that the rapid exchange grip strength test cannot reliably detect voluntary submaximal effort.

Ganglia: the patient's perception.

This study investigates the concerns of 50 patients with ganglia and their reasons for primary care consultation and referral to a hand unit. Although a minority of patients sought advice and treatment because of pain, more (38%) were concerned about the cosmetic appearance and a significant number (28%) were concerned that their ganglion was a malignant growth. The general practitioners referred 70% of patients to the hand clinic for "excision of the ganglion" and 30% for further "advice and treatment". However, 74% of patients were satisfied with aspiration of the ganglion and general advice.

Cone receptor sensitivity is altered in form deprivation myopia in the chicken.

PURPOSE: The effect of form deprivation myopia (FDM) on cone photoreceptor function was investigated. METHODS: Photopic electroretinogram (ERG) a-waves were recorded from control and form-deprived eyes of chickens. Cone-generated P3 responses were derived from the leading edge of ERG a-waves using an analytical expression derived from a quantitative model of phototransduction. The parameters obtained were the maximum cone P3 response (RmaxP3), sensitivity (S), and delay (t(d)). RESULTS: P3 response sensitivity is significantly higher in form-deprived eyes, at lower retinal irradiances. At higher flash intensities, in form-deprived eyes, P3 response sensitivity declines at a significantly greater rate, per unit increase in retinal irradiance, than in control eyes. Visual deprivation does not significantly affect RmaxP3 or t(d). CONCLUSIONS: Hypotheses to explain the altered cone photoreceptor sensitivity in form-deprived eyes are proposed. Changes in the biochemistry of phototransduction, or intrinsic geometric and physical attributes of photoreceptors or their waveguide modal properties, could account for the findings.

The use of a paediatric coma scale for monitoring infants and young children with head injuries.

Head injuries are a significant cause of morbidity and mortality in children. A descriptive multiple-case study was used to compare the accuracy of two assessment scales in children aged under 5 years. The study emphasised the importance of prompt and accurate assessment of children with head injuries. The Glasgow Coma Scale (GCS) is inappropriate for use in young children. The Adelaide Coma Scale (ACS) is a more appropriate tool for those aged under 5 years because it takes the child's age, and, therefore, neurological immaturity, into account. However, the ACS still does not give enough scope for assessment. If the ACS is used, therefore, additional information must be considered, including specific paediatric indicators, and an assessment of each child's behaviour according to the main care giver.

Formoguanamine-induced inhibition of deprivation myopia in chick is accompanied by choroidal thinning while retinal function is retained.

Twenty hatchling chickens were injected intravitreally every 4 days from day 2 to day 16 with dimethyl sulphoxide (DS) in one eye and DS or formoguanamine dissolved in DS (FG.DS) with or without occlusion in the other (FG.DS.MD, DS.MD, FG.DS). At day 16, the FG.DS.MD eyes failed to show the high refractive myopia and showed less axial elongation than that developed by the DS.MD eyes. Electroretinograms indicated that at the dosage used, FG.DS does not eliminate phototransduction. Light microscopy showed choroidal and retinal thinning in DS.MD and FG.DS.MD eyes but less than in FG.DS eyes, suggesting that change in choroidal thickness is unlikely to be the primary cause of form deprivation myopia.

Developmental expression of the prothoracicotropic hormone in the CNS of the tobacco hornworm Manduca sexta.

The prothoracicotropic hormone is an insect neuropeptide released into the hemolymph to signal molting and metamorphosis through its stimulation of steroidogenesis. The only known source of the prothoracicotropic hormone in the tobacco hornworm, Manduca sexta, has been a group of lateral cerebral neurosecretory cells, the L-NSC III. In this study, the developmental and spatial distribution of the prothoracicotropic hormone was examined throughout the life cycle of Manduca. In common with many vertebrates and invertebrates in which neuropeptides are located in several regions within the central nervous system (CNS), the prothoracicotropic hormone phenotype in Manduca is expressed by CNS neurons in addition to the L-NSC III. These neurons are located in the brain, frontal ganglion, and subesophageal ganglion. One cerebral neurosecretory cell group, the ventromedial neurons, expresses the prothoracicotropic hormone phenotype and the behavioral neurohormone, eclosion hormone. Whereas the L-NSC III and the ventromedial neurons express the peptide phenotype throughout the life cycle, the other neurons express the peptide only during the embryonic and larval stages. This precise spatial and temporal expression of the prothoracicotropic hormone by different groups of neurosecretory cells raises the possibility that in Manduca the peptide may, in addition to its known neuroendocrine function, play other physiological roles in different ways at different stages of the life cycle.

Identification of Ehrlichia chaffeensis morulae in cerebrospinal fluid mononuclear cells.

We report a case of ehrlichiosis in a 72-year-old man who developed extreme lethargy, acute renal failure requiring hemodialysis, and respiratory insufficiency requiring intubation. Lumbar puncture performed on the second day of hospitalization revealed significant cellular pleocytosis. Ehrlichia morulae were tentatively identified in mononuclear cells in routinely processed Wright-stained cytospin preparations of cerebrospinal fluid (CSF). Identification was confirmed by a specific immunocytochemical staining procedure. Subsequent identification specifically as Ehrlichia chaffeensis morulae was established by polymerase chain reaction analysis, which revealed E. chaffeensis-specific DNA in CSF, bone marrow, and blood samples; by indirect fluorescent-antibody analysis, the patient developed an antibody titer of 32,768 against E. chaffeensis antigen. The patient responded to intravenous therapy with doxycycline and dexamethasone. Subsequently, neurologic, hematologic, renal, and pulmonary status had returned to baseline at follow-up 12 weeks after admission. To our knowledge, this is the first identification of E. chaffeensis morulae in CSF cells in an infected patient.

Three-dimensional architecture of identified cerebral neurosecretory cells in an insect.

The organization of identified neurosecretory cell groups in the larval brain of the tobacco hornworm, Manduca sexta, was investigated immunocytologically. Computer-assisted three-dimensional reconstruction was used to examine the architecture of the neurosecretory cell groups. The group III lateral neurosecretory cells (L-NSC-III) which produce the prothoracicotropic hormone are located dorsolaterally in the protocerebrum and extend axons medially that decussate to the contralateral lobe prior to exiting the brain through the nervi corporis cardiaci I + II. The group IIa2 medial neurosecretory cells (M-NSC IIa2) are located anteriorly in the medial dorsal protocerebrum. The axons of these cells also exit the brain via the contralateral nervi corporis cardiaci I + II. However, their axons traverse a different pathway through the brain from that of the L-NSC III axons. Each of the cell groups possesses elaborate dendrites with terminal varicosities. The dendrites can be classified into specific fields based upon their location and projection pattern within the brain. The dendrites for these two neurosecretory cell groups overlap in specific regions of the protocerebral neuropil. After the axons of these neurosecretory cells exit the brain through the retrocerebral nerve, they innervate the corpus allatum where they arborize to form neurohemal terminals in strikingly different patterns. The L-NSC III penetrate throughout the glandular structure and the M-NSC IIa2 terminals are restricted to the external sheath. A third group of cerebral neurosecretory cells, the ventromedial neurons (VM) which stain with the monoclonal antibody to prothoracicotropic hormone in Manduca, are located anteriorly in the medial region of the brain. The axons of these cells do not exit the brain to the retrocerebral complex, but rather pass through the circumesophageal connectives and ventral nerve cord. These neurons appear to be the same VM neurons that produce eclosion hormone. One dendritic field of the L-NSC III terminates in close apposition to the VM neurons. The distinct morphologies of these neurosecretory cell groups in relation to other cell groups and the distribution of neuropeptides within the neurons suggest that insect neurosecretory cells, like their vertebrate counterparts, may have multiple regulatory roles.

The development of identified neurosecretory cells in the tobacco hornworm, Manduca sexta.

The prothoracicotropic hormone (PTTH) is a principal neuropeptide regulator of insect postembryonic molting and metamorphosis. In the tobacco hornworm, Manduca sexta, PTTH is produced by two neurosecretory cells (NSC) located in each protocerebral lobe of the brain. The development of these neurons, the L-NSC III, has been investigated immunocytologically to establish the time course of their morphological differentiation. PTTH may be one of the earliest neuropeptides expressed in insect embryos. PTTH-immunoreactivity was initially detected in the somata at 24 to 30% of embryonic development. Neurites sprouted shortly thereafter and began to grow medially through the brain anlage. By 42% embryonic development, the neurites had decussated to the contralateral brain lobe. As development progressed, the L-NSC III neurites grew along specific tracts through the contralateral brain lobe reaching the ventrolateral regions of the brain by approximately 60% development. The axons exited the brain through a retrocerebral nerve, the nervi corporis cardiaci I + II. At approximately 63% development, the axons innervated the corpus allatum and began branching to form neurohemal terminals for PTTH release. At 60% development, short collaterals began extending in the protocerebral neuropil. During the remainder of embryogenesis, both the dendritic collaterals and the terminal neurohemal varicosities continued to elongate and arborize. By 85% embryonic development, the basic architecture of the L-NSC III was established.