Moral insanity and psychological disorder: the hybrid roots of psychiatry.

This paper traces the significance of the diagnosis of 'moral insanity' (and the related diagnoses of 'monomania' and ' manie sans délire') to the development of psychiatry as a profession in the nineteenth century. The pioneers of psychiatric thought were motivated to explore such diagnoses because they promised public recognition in the high status surroundings of the criminal court. Some success was achieved in presenting a form of expertise that centred on the ability of the experts to detect quite subtle, 'psychological' forms of dangerous madness within the minds of offenders in France and more extensively in England. Significant backlash in the press against these new ideas pushed the profession away from such psychological exploration and back towards its medical roots that located criminal insanity simply within the organic constitution of its sufferers.

Sea-ice thermodynamics and brine drainage.

Significant changes in the state of the Arctic ice cover are occurring. As the summertime extent of sea ice diminishes, the Arctic is increasingly characterized by first-year rather than multi-year ice. It is during the early stages of ice growth that most brine is injected into the oceans, contributing to the buoyancy flux that mediates the thermo-haline circulation. Current operational sea-ice components of climate models often treat brine rejection between sea ice and the ocean similarly to a thermodynamic segregation process, assigning a fixed salinity to the sea ice, typical of multi-year ice. However, brine rejection is a dynamical, buoyancy-driven process and the salinity of sea ice varies significantly during the first growth season. As a result, current operational models may over predict the early brine fluxes from newly formed sea ice, which may have consequences for coupled simulations of the polar oceans. Improvements both in computational power and our understanding of the processes involved have led to the emergence of a new class of sea-ice models that treat brine rejection dynamically and should enhance predictions of the buoyancy forcing of the oceans.

Combined multiphoton microscopy and somatostatin receptor type 2 imaging of pancreatic neuroendocrine tumors.

Pancreatic neuroendocrine tumors (PNETs) are a rare but increasingly more prevalent cancer with heterogeneous clinical and pathological presentation. Surgery is the preferred treatment for all hormone-expressing PNETs and any PNET greater than 2 cm, but difficulties arise when tumors are multifocal, metastatic, or small in size due to lack of effective surgical localization. Existing techniques such as intraoperative ultrasound provide poor contrast and resolution, resulting in low sensitivity for such tumors. Somatostatin receptor type 2 (SSTR2) is commonly overexpressed in PNETs and presents an avenue for targeted tumor localization. SSTR2 is often used for pre-operative imaging and therapeutic treatment, with recent studies demonstrating that somatostatin receptor imaging (SRI) can be applied in radioguided surgery to aid in removal of metastatic lymph nodes and achieving negative surgical margins. However not all PNETs express SSTR2, indicating labeled SRI could benefit from using a supplemental label-free technique such as multiphoton microscopy (MPM), which has proven useful in improving the accuracy of diagnosing more common exocrine pancreatic cancers. Our work tests the suitability of combined SRI and MPM for localizing PNETs by imaging and comparing samples of PNETs and normal pancreatic tissue. Specimens were labeled with a novel SSTR2-targeted contrast agent and imaged using fluorescence microscopy, and subsequently imaged using MPM to collect four autofluorescent channels and second harmonic generation. Our results show that a combination of both SRI and MPM provides enhanced contrast and sensitivity for localizing diseased tissue, suggesting that this approach could be a valuable clinical tool for surgical localization and treatment of PNETs.

Pilot scale microbial fuel cells using air cathodes for producing electricity while treating wastewater.

Microbial fuel cells (MFCs) can generate electrical energy from the oxidation of the organic matter, but they must be demonstrated at large scales, treat real wastewaters, and show the required performance needed at a site to provide a path forward for this technology. Previous pilot-scale studies of MFC technology have relied on systems with aerated catholytes, which limited energy recovery due to the energy consumed by pumping air into the catholyte. In the present study, we developed, deployed, and tested an 850 L (1400 L total liquid volume) air-cathode MFC treating domestic-type wastewater at a centralized wastewater treatment facility. The wastewater was processed over a hydraulic retention time (HRT) of 12 h through a sequence of 17 brush anode modules (11 m2 total projected anode area) and 16 cathode modules, each constructed using two air-cathodes (0.6 m2 each, total cathode area of 20 m2) with the air side facing each other to allow passive air flow. The MFC effluent was further treated in a biofilter (BF) to decrease the organic matter content. The field test was conducted for over six months to fully characterize the electrochemical and wastewater treatment performance. Wastewater quality as well as electrical energy production were routinely monitored. The power produced over six months by the MFC averaged 0.46 ± 0.35 W (0.043 W m-2 normalized to the cross-sectional area of an anode) at a current of 1.54 ± 0.90 A with a coulombic efficiency of 9%. Approximately 49 ± 15 % of the chemical oxygen demand (COD) was removed in the MFC alone as well as a large amount of the biochemical oxygen demand (BOD5) (70%) and total suspended solid (TSS) (48%). In the combined MFC/BF process, up to 91 ± 6 % of the COD and 91 % of the BOD5 were removed as well as certain bacteria (E. coli, 98.9%; fecal coliforms, 99.1%). The average effluent concentration of nitrate was 1.6 ± 2.4 mg L-1, nitrite was 0.17 ± 0.24 mg L-1 and ammonia was 0.4 ± 1.0 mg L-1. The pilot scale reactor presented here is the largest air-cathode MFC ever tested, generating electrical power while treating wastewater.

A Case Report on Type 2 Amiodarone Induced Thyrotoxicosis and Hypercalcemia.

Amiodarone, the most commonly used antiarrhythmic drug, can cause either hypothyroidism by inhibiting iodide transport into the thyroid gland or hyperthyroidism. We present a rare case of type 2 amiodarone-induced thyrotoxicosis with hypercalcemia. A 64-year-old man with systolic heart failure, hypertension, and hyperthyroidism presented with complaints of dyspnea on exertion, orthopnea, and vomiting for several days. Laboratory tests showed low thyroid stimulating hormone <0.01 mIU/L, high free triiodothyronine (FT3) of 24.8 ng/dL, free thyroxine (FT4) of >5.0 ng/dL, and hypercalcemia of 12.9 mg/dL. Hypercalcemia, a rare presentation of AIT, was treated with calcitonin and intravenous fluids. The patient was taken off methimazole and started on propylthiouracil for the persistent elevation of thyroid hormones, especially FT3, and to reduce the conversion of T4 to T3. The patient was not completely responding to treatment with propylthiouracil alone, so prednisone was added to the regimen on day 12, effectively returning the patient to the euthyroid state.

From WOEST to AUGUSTUS: a review of safety and efficacy of triple versus dual antithrombotic regimens in patients with atrial fibrillation requiring percutaneous coronary intervention for acute coronary syndrome.

For patients with atrial fibrillation with concomitant acute coronary syndrome (ACS) requiring percutaneous coronary intervention (PCI), the increased risk of bleeding associated with the use triple therapy is well established. However, there is question whether it is a necessary risk for patients to prevent stroke and stent thrombosis. The purpose of this article is to highlight the findings of prior studies evaluating the comparative safety and efficacy of dual and triple antithrombotic regimens in the subgroup of atrial fibrillation patients requiring PCI for ACS. Trials that evaluated dual versus triple antithrombotic therapy demonstrated post-PCI treatment with a P2Y12 inhibitor alone was safer than aspirin plus a P2Y12 inhibitor in patients also taking an anticoagulant for atrial fibrillation. Data regarding ischemic outcomes have not suggested harm with the omission of aspirin, but these studies have not been powered to assess efficacy outcomes, especially in ACS patients. These studies also demonstrate a significant reduction in bleeding events when aspirin is excluded from the post-PCI regimen in the ACS subgroup of atrial fibrillation patients. Further studies, with added focus on the ACS subgroup, are needed to potentially confirm that dual therapy may be as efficacious as triple therapy in ACS patients with atrial fibrillation.

Changes in cardiorespiratory fitness and coronary heart disease risk factors following 24 wk of moderate- or high-intensity exercise of equal energy cost.

This study was designed to investigate the effect of exercise intensity on cardiorespiratory fitness and coronary heart disease risk factors. Maximum oxygen consumption (Vo(2 max)), lipid, lipoprotein, and fibrinogen concentrations were measured in 64 previously sedentary men before random allocation to a nonexercise control group, a moderate-intensity exercise group (three 400-kcal sessions per week at 60% of Vo(2 max)), or a high-intensity exercise group (three 400-kcal sessions per week at 80% of Vo(2 max)). Subjects were instructed to maintain their normal dietary habits, and training heart rates were represcribed after monthly fitness tests. Forty-two men finished the study. After 24 wk, Vo(2 max) increased by 0.38 +/- 0.14 l/min in the moderate-intensity group and by 0.55 +/- 0.27 l/min in the high-intensity group. Repeated-measures analysis of variance identified a significant interaction between monthly Vo(2 max) score and exercise group (F = 3.37, P < 0.05), indicating that Vo(2 max) responded differently to moderate- and high-intensity exercise. Trend analysis showed that total cholesterol, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and fibrinogen concentrations changed favorably across control, moderate-intensity, and high-intensity groups. However, significant changes in total cholesterol (-0.55 +/- 0.81 mmol/l), low-density lipoprotein cholesterol (-0.52 +/- 0.80 mmol/l), and non-high-density lipoprotein cholesterol (-0.54 +/- 0.86 mmol/l) were only observed in the high-intensity group (all P < 0.05 vs. controls). These data suggest that high-intensity training is more effective in improving cardiorespiratory fitness than moderate-intensity training of equal energy cost. These data also suggest that changes in coronary heart disease risk factors are influenced by exercise intensity.

Factor XII auto-antibodies present in a patient with a B-cell lymphoma.

A 64-year-old woman was transferred for investigation of a mediastinal mass, biopsy of which showed a diffuse large B-cell lymphoma. She was also found to have an antiphospholipid antibody. The pre-operative coagulation screen showed a prolonged activated partial thromboplastin time, 71.3 s (normal range, 26-36 s), which was not corrected by the addition of normal plasma. The dilute Russell's viper venom time was positive. Anti-cardiolipin assay was strongly positive, immunoglobulin M was 153 AU; immunoglobulin G was normal, 3.1 AU. Assays of factors VIII, IX and XI showed higher concentrations with increasing dilutions in one-stage factor assays from 1: 10 to 1: 80 suggestive of an inhibitor. Factor XII was 9 U/dl and results were unaffected by increasing dilution, suggesting specific antibodies to factor XII. The factor XII antigen was 40 U/dl. The patient had immunoglobulin M auto-antibodies to factor XII.

Solidification of a disk-shaped crystal from a weakly supercooled binary melt.

The physics of ice crystal growth from the liquid phase, especially in the presence of salt, has received much less attention than the growth of snow crystals from the vapor phase. The growth of so-called frazil ice by solidification of a supercooled aqueous salt solution is consistent with crystal growth in the basal plane being limited by the diffusive removal of the latent heat of solidification from the solid-liquid interface, while being limited by attachment kinetics in the perpendicular direction. This leads to the formation of approximately disk-shaped crystals with a low aspect ratio of thickness compared to radius, because radial growth is much faster than axial growth. We calculate numerically how fast disk-shaped crystals grow in both pure and binary melts, accounting for the comparatively slow axial growth, the effect of dissolved solute in the fluid phase, and the difference in thermal properties between solid and fluid phases. We identify the main physical mechanisms that control crystal growth and show that the diffusive removal of both the latent heat released and the salt rejected at the growing interface are significant. Our calculations demonstrate that certain previous parametrizations, based on scaling arguments, substantially underestimate crystal growth rates by a factor of order 10-100 for low aspect ratio disks, and we provide a parametrization for use in models of ice crystal growth in environmental settings.

Plasma levels of factor XII, prekallikrein and high molecular weight kininogen in normal blood donors and patients having suffered venous thrombosis.

INTRODUCTION: The contact system proteins factor XII (FXII), prekallikrein (PK) and high molecular weight kininogen (HK) have roles in coagulation, fibrinolysis, thrombin-induced platelet activation, cell adhesion and angeogenisis. It has been suggested that inherited or acquired deficiencies of these proteins may be risk factors for thrombosis. Studies on the levels of FXII in plasma from normal and thrombotic patient populations have been reported, to our knowledge however, no systematic study on plasma levels of PK and HK in large populations of normal blood donors and patients having had venous thrombotic events has been performed. MATERIALS AND METHODS: Chromogenic substrate assays were used to measure plasma levels of FXII, PK and HK in 300 normal blood donors (ND) and 300 patients attending our anticoagulant clinic who had a history of venous thrombosis (deep vein thrombosis or pulmonary embolism [VT]). All subjects were Caucasian, antiphospholipid antibody negative and had normal liver function. RESULTS: Mean values +/- SD were: FXII: ND 99.4 +/- 26.7%: VT 91.0 +/- 27.2%: PKK: ND 99.7 +/- 19.8%: VT 99.1 +/- 21.2%: HK: ND 101.0 +/- 20.5%: VT 110.7 +/- 32.3%. Statistical analysis of the data revealed significantly lower (p< or =0.001) mean values for FXII and significantly higher (p< or =0.001) mean values for HK in the VT group. Calculated lower limits of normal for each parameter were: FXII: 49.1%, PKK: 66.8%, HK: 63.4%. The prevalence of values below the lower limit of normal were FXII-ND 2.3%: FXII-VT 8.0%, PKK-ND 3.0%: PKK-VT 4.7%, HK-ND 2.3%: HK-VT 5.0%. No homozygous deficiency patients were found for any parameter. One VT patient had combined FXII and HK deficiency and one ND and two VT patients had combined PK and HK deficiency. CONCLUSIONS: FXII levels were lower and HK levels and the prevalence of FXII, PK and HK deficiency higher in a population of patients with a history of VT than in a population of healthy blood donors.

Cooling of cilia allows functional analysis of the beat pattern for diagnostic testing.

BACKGROUND: Reports of the effect of low temperatures on ciliary beat frequency (CBF) are conflicting, and the effect on ciliary beat pattern has not been reported. We aimed to clarify this association and determine whether cooling of cilia may allow ciliary function to be assessed without the need of expensive high-speed video microscopy. METHODS: Fourteen nasal brush biopsy samples were collected, and the CBF and beat pattern of undisrupted ciliated edges were evaluated. Two methods were used to strictly control changes in temperature: One enabled rapid transitory measurements during cooling and warming, and the other was used to maintain accurate low temperatures over longer periods of time. RESULTS: A sigmoid relationship between CBF and temperature was observed. CBF decreased with cooling and increased with warming. Ciliary function was unaffected by the direction of temperature change and was maintained down to 2°C. The percentage of dyskinetic cilia observed at 2°C or 4°C was unchanged from that at 37°C. CONCLUSIONS: Contrary to previous research, our data show that cilia continue to beat with a normal pattern at temperatures as low as 2°C. Slowing of cilia by cooling may allow detailed analysis of ciliary beat pattern without the need of expensive high-speed video microscopy.

Thrombin generation: a comparison of assays using platelet-poor and -rich plasma and whole blood samples from healthy controls and patients with a history of venous thromboembolism.

We have developed a whole blood thrombin generation (TG) assay whereby TG is initiated with a low-tissue factor concentration and monitored using a fluorogenic thrombin substrate. Significantly higher values were found in blood samples from 50 patients with a history of venous thromboembolism (VTE) compared with 31 healthy controls (HC), for peak height (P = 0.0034) and endogenous thrombin potential (ETP) (P = 0.0027). Results from 31 VTE patients and the 31 controls in the absence of corn trypsin inhibitor (CTI) showed significantly higher values in the VTE group for peak height (P = 0.0013) and ETP (P = 0.002). In the presence of CTI, significantly higher values were only seen in ETP (P = 0.024). No significant increases in TG were found using platelet poor (PPP) or -rich (PRP) plasma with or without CTI. The whole blood TG assay in the absence or presence of CTI showed a higher proportion (25/50 and 12/31, respectively) of raised peak height and/or ETP values than plasma assays (PPP 9/50 and 5/31 respectively and PRP 13/50 and 6/31, respectively). Our results show the whole blood TG assay is more sensitive for determining the increases in TG in patients with a history of VTE than PPP and PRP TG assays.