Optical computation of a spin glass dynamics with tunable complexity.

Spin glasses (SGs) are paradigmatic models for physical, computer science, biological, and social systems. The problem of studying the dynamics for SG models is nondetermistic polynomial-time (NP) hard; that is, no algorithm solves it in polynomial time. Here we implement the optical simulation of an SG, exploiting the N segments of a wavefront-shaping device to play the role of the spin variables, combining the interference downstream of a scattering material to implement the random couplings between the spins (the [Formula: see text] matrix) and measuring the light intensity on a number P of targets to retrieve the energy of the system. By implementing a plain Metropolis algorithm, we are able to simulate the spin model dynamics, while the degree of complexity of the potential energy landscape and the region of phase diagram explored are user defined, acting on the ratio [Formula: see text] We study experimentally, numerically, and analytically this Hopfield-like system displaying a paramagnetic, ferromagnetic, and SG phase, and we demonstrate that the transition temperature [Formula: see text] to the glassy phase from the paramagnetic phase grows with α. We demonstrate the computational advantage of the optical SG where interaction terms are realized simultaneously when the independent light rays interfere on the detector's surface. This inherently parallel measurement of the energy provides a speedup with respect to purely in silico simulations scaling with N.

From policy to practice: challenges in infant feeding in emergencies during the Balkan crisis.

The preparation and dissemination of policy statements are necessary but insufficient to prevent the inappropriate use of infant-feeding products in emergencies. The widespread failure of humanitarian agencies operating in the Balkan crisis to act in accordance with international policies and recommendations provides a recent example of the failure to translate infant-feeding policies into practice. This article explores the underlying reasons behind the failures which include: (1) the weak institutionalisation of policies; (2) the massive quantities of unsolicited donations of infant-feeding products: (3) the absence of monitoring systems; (4) inadequate co-ordination mechanisms; (5) the high costs of correcting mistakes; and (6) the cumulative effects of poor practice. Efforts to uphold best practice during the crisis are also documented. Finally, the article identifies actions that could be undertaken in advance of and during future emergencies to enhance the application of infant feeding policies in emergencies.

[MIDOS--validation of a minimal documentation system for palliative medicine]. / MIDOS Validierung eines minimalen Dokumentationssystems für die Palliativmedizin.

INTRODUCTION: Repeated assessment of pain and other symptoms is required for quality assurance in palliative care. However, physical and cognitive impairment of the patients may impede the use of standardized questionnaires and documentation systems in palliative care setting. We developed a minimal documentation system (MIDOS) for the specific requirements in this setting. METHODS: The German versions of the Brief Pain Inventory (BPI) and the quality of life questionnaire SF-12 were completed for all patients admitted to the palliative care unit. Cognitive impairment was assessed with the Mini Mental State Examination (MMSE). With admission as well as on subsequent consultations patients self-assessed average and maximum pain intensity on numeric rating scales and the intensity of drowsiness, nausea, constipation, dyspnea, weakness, anxiety and well-being on verbal categorical scales. RESULTS: From August 1998 to June 1999 128 patients were documented consecutively. Fifty-nine percent of these patients were treated with WHO-step 3 opioids. Cognitive impairment (MMSE<24) was present in 37% of the patients. Self-assessment with MIDOS was possible for 114 patients at the time of admission, and for 108 patients at the end of therapy. Pain, drowsiness and weakness were documented by most patients, whereas the other symptoms were reported less frequently. DISCUSSION: Factor analysis showed one factor for pain and two factors for the other symptoms. The pain sum score of MIDOS correlated with the factors of the BPI, the symptom sum score of MIDOS correlated with the factors of the BPI and the mental sum score of the SF-12, though on a lower level. MIDOS sum scores showed good pain relief and symptom control for patients discharged home or to other services, whereas the symptom sum score gave an indication of the deterioration in the terminal phase for those patients who died during in-patient treatment. Test-retest stability was good for a subgroup of patients with stable opioid doses. CONCLUSIONS: We conclude that MIDOS is a valid instrument for self-assessment of the patient's symptoms and may be used to monitor the efficacy of symptom management.

Complex feedback regulation of bile acid synthesis in the hamster: the role of newly synthesized cholesterol.

Hepatic bile acid synthesis is regulated by recirculating bile acids, possibly by modulating the availability of newly synthesized and preformed cholesterol. Because data in the hamster on this mechanism are lacking, we fitted these animals with an extracorporeal bile duct and administered tritiated water intraperitoneally to label newly formed cholesterol. After interruption of the enterohepatic circulation, physiological and double-physiological doses of conjugated cholate (25 or 50 micromol/100 g. h) or of unconjugated deoxycholate (6 or 12 micromol) were infused intraduodenally for 54 hours and compared with controls. De novo and preformed cholesterol directly secreted into bile or used for cholate and chenodeoxycholate synthesis were quantitated by high-pressure liquid chromatography (HPLC)-liquid scintillation. Directly after depletion of the bile acid pool (6-9 hours) at nearly physiological conditions, chenodeoxycholate synthesis was significantly reduced by cholate and deoxycholate by up to 45% to 51%, whereas cholate formation decreased by approximately 22% during deoxycholate. This short-term effect was mainly mediated by reduced synthesis from preformed cholesterol. After long-term bile depletion (30-54 hours), bile acid synthesis returned to control levels during 25 micromol of cholate and of both deoxycholate doses. In contrast, only 50 micromol of cholate prevented derepression of bile acid synthesis. This long-term effect was mainly attributed to a diminished formation from de novo cholesterol exceeding the reduced synthesis from preformed cholesterol. In summary, short- and long-term regulation of bile acid synthesis in hamsters differs with respect to availabilities of preformed and de novo cholesterol.

-Recanalization of chronic coronary artery occlusions: effect on clinical symptoms and left ventricular function-. / Rekanalisation chronischer Koronararterienverschlüsse: Einfluss auf klinisches Beschwerdebild und linksventrikuläre Funktion.

UNLABELLED: Angioplasty of chronically occluded coronary arteries is discussed controversially. This study was performed to investigate the potential benefit of recanalization procedures. Between 1/91 and 10/93 occlusion angioplasty was attempted in 408 patients. 322 persons were followed with repeat angiography performed in 177 patients. Quantitative analysis of left ventricular function was performed in 34 patients before and after successful occlusion angioplasty. Primary reopening rate was about 71% with highest success rate for occluded LAD (82%). Angiographic controls showed open arteries in 80 (45.2%) patients, 53 (30.0%) had restenosis and 44 (24.8%) reocclusion. Anginal status was improved by one CCS-class or more in 197 patients (61%), mean exercise workload increased from 115.8 watts to 136.1 watts (p < 0.0001). Out of 34 patients, 25 (73.5%) showed improvement of regional ventricular function, mean ejection fraction increased from 56.9% to 64.1% (p < 0.001). Follow-up angiography revealed open arteries in 58% of patients if dissection was absent. When dissection type B, C or D NHLBI was present, only 32% of the vessels were open. CONCLUSION: In selected patients occlusion angioplasty is feasible with acceptable primary results. Anginal complaints and functional status were influenced positively, left ventricular function showed improvement indicating the presence of hibernating myocardium. In patients with suboptimal primary results (dissection) repeat angiography may be indicated.

[Results of immediate and delayed bypass operation in PTCA emergencies]. / Ergebnisse der sofortigen und der verzögerten Bypass-Operation beim PTCA-Notfall.

UNLABELLED: The therapeutic strategy for irreversible coronary occlusion as a complication of PTCA is influenced by the rate of myocardial infarctions and mortality after emergency bypass surgery. If immediate bypass operation cannot prevent myocardial infarction, medication will be the treatment of choice. Since the duration of ischemia is of critical importance for the preservation of myocardium, we analyzed our results with respect to the time interval from the onset of ischemia to surgery. From 12/84 to 12/93 there were 49 emergency operations for 4,478 PTCAs. In 38 patients acute closure occurred in the cath lab; because of very strict standby arrangements these patients could be brought to the operating rooms without delay (group A). In 11 patients acute closure occurred during the following 24 hours in the intermediate care unit (group B); attempts of catheter recanalisation and/or preparation for surgery accounted for an additional time delay until surgery of 79 minutes. RESULTS: In the 38 patients of group A there were only one small transmural (CKmax 533/U/l) and four non-Q wave (CK-max 322 U/l) myocardial infarctions. Of the 11 patients in group B only two did not suffer any loss of myocardium. In seven cases there were transmural (CKmax 1,296 U/l) and in two cases non-Q wave (CKmax 721 U/l) myocardial infarctions. Two patients of group B died on the second and third postoperative day. Thus the results of emergency bypass operations were excellent if surgery could be performed immediately after failure of catheter interventions (all survived, no transmural M.I. in 97%).(ABSTRACT TRUNCATED AT 250 WORDS)

Biliary cholesterol secretion and bile acid formation in the hamster: the role of newly synthesized cholesterol.

In order to define the source of cholesterol for bile acid synthesis and biliary cholesterol, hamsters with an extracorporeal bile duct received an intraperitoneal bolus of [3H]water labeling newly synthesized cholesterol. Thereafter the enterohepatic circulation was interrupted and a nutrient solution was infused during the experimental period of 78 h. In a separate group, pravastatin was administered (54-78 h) to allow discrimination of 3H-labeled cholesterol recycling from plasma and newly synthesized hepatic cholesterol late during the experiment. In controls, newly synthesized biliary cholesterol and primary bile acids derived from cholesterol newly synthesized during the experiment amounted to 5% and 12% immediately after depletion of the bile acid pool (6-9 h), respectively. After longterm bile diversion these proportions increased to 56-63%, whereas 71% of plasma cholesterol was labeled. Pravastatin inhibited the secretion of biliary cholesterol, cholate, and chenodeoxycholate by 30, 50, and 44%, respectively. In contrast, the preinfusion tritium label was suppressed by a maximum of 16%, 14%, and 26%, respectively, reflecting the contribution of cholesterol newly synthesized in the hepatocyte as opposed to labeled cholesterol recycling from the plasma. It is concluded that in the hamster newly synthesized cholesterol is of minor importance as substrate for bile acid synthesis as well as biliary cholesterol, both under near physiologic conditions and after long-term bile diversion. Moreover, the hepatic cholesterol pools subserving the synthesis of the primary bile acids are identical but appear to be different from that of biliary cholesterol directly after the depletion of the enterohepatic bile acids.

Bile acid synthesis from newly synthesized vs. preformed cholesterol precursor pools in the rat.

The present study defines the origin of cholesterol subserving bile acid synthesis in male rats with an extracorporal bile duct by labeling newly formed cholesterol with tritiated water. Within 6 hr after interruption of the enterohepatic circulation, the bile acid pool was depleted. At this early time point the proportion from de novo cholesterol was 8% and 12% for biliary cholesterol and cholate, but 18% and 19% for muricholate and chenodeoxycholate, respectively. This proportion gradually rose to 40%, 34%, 51% and 51%, respectively, at 15 to 30 hr. At 78 hr after bile diversion, 64% of cholate was labeled, compared with 84% to 88% of the other biliary lipids and 71% of plasma cholesterol. Total and labeled bile acid secretion exhibited the same diurnal rhythm. To allow differentiation between direct hepatocytic de novo synthesis of bile acids from acetate and recycling of labeled plasma cholesterol, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (pravastatin) was infused from 54 to 78 hr. It suppressed total synthesis of primary bile acids by 60% to 80% but decreased the tritium label of bile acids only from a range of 74% to 92% (54 hr) to a range of 54% to 63% (78 hr), which was in the range of plasma cholesterol (58%). We conclude that bile acids and biliary cholesterol are synthesized mostly from preformed (i.e., plasma) cholesterol, both immediately after depletion of the pool in enterohepatic circulation and after derepression. Moreover, the hepatic cholesterol pools subserving the synthesis of different bile acids and biliary cholesterol secretion are not identical.

Enterohepatic circulation in hamsters with an extracorporeal bile duct.

The present study describes a novel technique for investigations of the enterohepatic circulation in the hamster with an extracorporeal bile duct that allows long-term bile collection in the free-moving animal. The animals recovered for 7 days after the operation before the external loop was cut and bile was collected over a period of 78 h. Under these optimal conditions, initial bile flow (651 +/- 89 microliters per 100 g.h-1) and the secretion rates of biliary lipids were several-fold higher than reported in an earlier study using the acute fistula hamster. Biliary cholesterol secretion amounted to 369 +/- 32 nmol per 100 g.h-1, phospholipid secretion was 2.6 +/- 0.3 mumol per 100 g.h-1, and total bile acid secretion was 31.9 +/- 2.2 mumol per 100 g.h-1. A clearcut diurnal rhythm was demonstrated for bile flow and all biliary constituents. After 9 h the depletion of the bile acid pool was complete and cholic acid synthesis derepressed 1.4-fold from a basal rate of 818 nmol per 100 g.h-1, whereas the derepression of chenodeoxycholic acid synthesis was even less pronounced. Biliary cholesterol output increased 2.2-fold, but the phospholipid secretion was constant during the full experiment. It may be concluded that the technique of an extracorporeal bile duct in the free-moving animal allows studies of bile secretion under optimal conditions. Most likely the bile secretion rates given above approach the physiological rates in the hamster.

[Immediate bypass operation prevents heart infarct in PTCA emergencies]. / Die sofortige Bypass-Operation verhindert den Herzinfarkt beim PTCA-Notfall.

UNLABELLED: Between December 1984 and June 30, 1989, we performed PTCAs on 1438 patients. The procedures were performed with strict cardiosurgical standby. In 24 patients (22 X LAD, 2 X RCA), abrupt coronary occlusion necessitated immediate bypass surgery. In 19 cases, abrupt coronary closure occurred during PTCA in the cath lab; in five patients, during the following 24 h on the intermediate care ward. No patient died. Immediate bypass surgery prevented myocardial infarction (MI) in 79.2% of the cases. None of the 19 patients with abrupt coronary closure in the cath lab had a Q-wave myocardial infarction postoperatively. One of these 19 patients had an R-wave reduction (non-Q-MI) and one patient had a new terminally negative T-wave in the postoperative ECG. Two of the five patients with evidence of acute coronary occlusion on the intermediate care ward had small Q-wave MIs and one had a non-Q-wave MI postoperatively. Time of ischemia (defined als time interval between the end of PTCA and the beginning of extracorporal circulation) was 65 +/- 28 min in the former group and 122 +/- 30 min in the latter. CONCLUSION: Because immediate bypass surgery prevents Q-wave MI after abrupt closure during PTCA, strict temporal and spatial cooperation with the cardiac surgeon is mandatory.

[Coronary spasm immediately following coronary revascularization]. / Koronarspasmus unmittelbar nach Koronarrevaskularisation.

Of 2,600 coronary operations performed from August 1983, to December 1988, two ischemic reactions of the inferior wall immediately after operation were observed. In both patients the right coronary artery was either dissected or revascularized intraoperatively. Under the diagnosis of postoperative spasm both patients had reangiography three hours after surgery. Right coronary artery spasm was demonstrated in both patients. After intracoronary injection of calcium channelblockers the spasm resolved completely. Patient 1 demonstrated a small inferior infarction during control angiography, patient 2 remained free of a myocardial infarction. The possible causes of coronary spasm during or after surgery are discussed. The diagnosis and an approach to therapy are outlined.

[Balloon dilatation of calcified aortic stenosis]. / Ballondilatation verkalkter Aortenstenosen.

Between November 1986 and March 1987, 14 patients (11 men and three women, aged 48-84 years, mean 71.3 years) had percutaneous transluminal balloon dilatation of calcific aortic valve stenosis. Peak transvalvar pressure gradients were reduced from a mean of 81.4 mm Hg (25-122 mm Hg) to a mean of 44.8 mm Hg (range 19-63 mm Hg). Calculated valve opening area was increased from a mean of 0.48 (0.3-0.86) cm2 to 0.75 (0.6-1.16) cm2. All but one patient were in stage III or IV (New York Heart Association) and most improved by about one stage. There were no complications that could be ascribed to the procedure. Blood transfusion was not required.

[Vigilance behavior in interaction of the serotonin-selective antidepressant zimelidine and parenterally administered ethanol]. / Vigilanzverhalten bei Interaktion des Serotonin-selektiven Antidepressivums Zimelidin mit parenteral verabreichtem Alkohol.

A randomized, placebo-controlled double-blind crossover study was carried out in 8 healthy male subjects to evaluate the interaction of (Z)-3-(4-bromphenyl)-N,N-dimethyl-3-(3-pyridyl)-allylamine-dihydrochloride-monohydrate (zimelidine, Normud) -- a new antidepressive drug -- and alcohol. New methodological approaches to the problem consisted in a parenteral application of ethanol and the introduction of the computer-assisted Oculodynamic Test -- a new multi-dimensional psychophysiological research instrument -- monitoring saccadic eye movements, choice-reaction parameters and cardiorespiratory parameters. Classical disimprovement of these parameters after ethanol infusion (equivalent to 1 mg % BEC) could be seen up to 5 h after administration. Alcohol effects were not potentiated by the selective serotonin-reuptake inhibitor zimelidine -- in contrary even a significant vigilance-stabilizing effect and improvement against placebo/ethanol values could be demonstrated for most of the vigilance-related parameters.

A pilot study to evaluate the effect of acute and long-term administration of cyclandelate on the vigilance of subjects submitted to hypoxic conditions. Preliminary report.

A pilot study of a double-blind crossover design was carried out in four healthy male volunteers. 3,5,5-Trimethylcyclohexyl mandelate (cyclandelate, Cyclospasmol) 800 mg b.d. was compared with placebo using two-week treatment periods separated by a wash-out-period. Under hypoxic conditions (11.5% O2) the volunteers were asked to perform a series of tests including a computer-assisted oculodynamic test (ODT) after one dosage and after fourteen days' treatment with both cyclandelate or placebo. ODT is a very sensitive test which is independent of learning or motivation. Certain cardiovascular and respiratory parameters were simultaneously recorded during the test periods. The results showed that cyclandelate protected the volunteers against the effects of hypoxia. The results after two weeks' treatment were more definite than those after the first dose, suggesting that cyclandelate acted centrally on cerebral metabolism rather than through a direct cerebrovascular effect.