Pareto Optimization and Tuning of a Laser Wakefield Accelerator.

Optimization of accelerator performance parameters is limited by numerous trade-offs, and finding the appropriate balance between optimization goals for an unknown system is challenging to achieve. Here, we show that multiobjective Bayesian optimization can map the solution space of a laser wakefield accelerator (LWFA) in a very sample-efficient way. We observe that there exists a wide range of Pareto-optimal solutions that trade beam energy versus charge at similar laser-to-beam efficiency. Moreover, many applications such as light sources require particle beams at certain target energies. We demonstrate accurate energy tuning of the LWFA from 150 to 400 MeV via the simultaneous adjustment of eight parameters. To further advance this use case, we propose an inverse model that allows a user to specify desired beam parameters. Trained on the forward Gaussian process model, the inverse model generates input parameter value ranges within which the desired setting is likely to be reached. The method reveals different strategies for accelerator tuning and is expected to drastically facilitate the operation of LWFAs in the near future.

Persistent effects of cognitive-behavioral stress management on cortisol responses to acute stress in healthy subjects--a randomized controlled trial.

Psychosocial stress leads to a release of cortisol. While this psychoneuroendocrine response helps to maintain physiological as well as psychological equilibrium under stress, exaggerated secretion of cortisol has been shown to have negative effects on somatic health and cognitive functioning. The study set out to examine the long-term effects of cognitive-behavioral stress management training on cortisol stress responses in healthy men and women. Eighty-three healthy subjects were randomly assigned to cognitive-behavioral stress management (CBSM) training or a control condition. Four months after the CBSM, 76 subjects underwent a standardized psychosocial stress test. Salivary cortisol responses were assessed repeatedly before and after the stress test. Subjects in the CBSM group showed significantly reduced cortisol stress responses. With regard to gender, this effect was observed in both men and women. However, the magnitude of the CBSM effect on cortisol responses was smaller in women than in men. Use of oral contraceptives in women influenced the cortisol response, but did not have an impact on the CBSM effect on cortisol. The results show that the previously reported attenuation of cortisol stress responses through CBSM persists and are observable in both men and women. Since stress-induced alterations of hypothalamus pituitary adrenal axis functioning are discussed to be involved in the onset and maintenance of both somatic and psychiatric conditions, similar interventions could be used for prevention and therapy of these detrimental stress effects.

Mechanical consequences of rod contouring and residual scoliosis in sublaminar segmental instrumentation.

The mechanical performance of contoured Luque rods in a neuromuscular model of spine deformity was examined to define an upper limit of deformity above which rod stresses would exceed the endurance limit for 316L stainless steel and therefore predict fatigue failure. Bovine constructs varying from 0-120 degrees scoliosis were loaded axially, with strain recordings obtained at the apex of the curve. Relatively low loads produced enough tensile stress to contemplate implant fatigue in all except the nondeformed (0 degrees) construct. Construct stiffness was found to decrease rapidly in spines with greater than 38 degrees deformity. In addition, data on patients who had suffered rod fracture from four different centers were found to compare favorably with experimental observations. We conclude that the vulnerability of Luque rod constructs to implant failure, from a mechanical standpoint, is greater than is generally assumed. Cross-linking of rods was found to increase stiffness. Methods to decrease tensile stresses in the implants and increase stiffness include external immobilization, larger diameter rods, and procedures to enhance correction.

The phytoestrogens Genistein and Daidzein, and 17 beta-estradiol inhibit development of neointima in aortas from male and female rabbits in vitro after injury.

BACKGROUND: 17 beta-Estradiol and phytoestrogens are known to have beneficial effects on the cardiovascular systems of women. The exact mechanisms for how estrogens and phytoestrogens influence the cardiovascular system are not yet understood in detail. OBJECTIVE: The objective of this study was to investigate whether 17 beta-estradiol and the phytoestrogens Genistein and Daidzein have an effect on post-injury processes in vessel walls. METHODS: In this in-vitro experiment, the sex-specific effects of 50 micrograms/ml 17 beta-estradiol (equivalent to 180 mumol/l), and of the isoflavones Genistein (5 and 50 micrograms/ml, equivalent to 18.5 and 185 mumol/l), and Daidzein (5 and 50 micrograms/ml, equivalent to 19.7 and 197 mumol/l) on endothelium-denuded aortas from female and male rabbits after vascular injury were studied. Morphometry and immunohistochemistry were performed for quantitative and qualitative analysis. RESULTS: Neointimal cells were in part positive for alpha-actin staining of smooth muscle cells. Staining with 5'-bromo-2'deoxyuridine plus 2'-deoxycytidine showed that proliferative activity in the neointima had significantly decreased after 28 days for groups that had been treated with 50 micrograms/ml Genistein. Immunofluorescence staining for the expression of nuclear estrogen receptor protein in the arterial wall for aortic rings from female and male rabbits was positive. 17 beta-Estradiol, Genistein, and its analog Daidzein (with no protein tyrosine kinase activity) inhibited formation of neointima sex-independently at equivalent concentrations of 50 micrograms/ml. However, a concentration of 5 micrograms/ml Genistein decreased formation of neointima significantly for aortic rings from male rabbits only, whereas 5 micrograms/ml Genistein increased formation of neointima in rings from female rabbits, which corresponded to the increase in proliferative activity detected after 28 days. CONCLUSION: Genistein and Daidzein both inhibited proliferation at certain concentrations, so this effect is supposed to be independent from Genistein's protein tyrosine kinase activity. The antiproliferative properties of all three estrogens were observed in the absence of endothelium and therefore are independent from endothelium-mediated effects.

Failure of fixation after segmental spinal instrumentation without arthrodesis in the management of paralytic scoliosis.

Between April and October 1981, nineteen children who were between five and twelve years old (median age, seven years), and who had severe paralytic scoliosis secondary to poliomyelitis, were treated by segmental spinal instrumentation without arthrodesis. Three patients could not be followed, and the cases of the remaining sixteen patients were reviewed in April 1984. In fifteen patients, the implant system had failed to control the deformity. In six patients, the rods had fractured at the apex of the original deformity; in five, longitudinal shift of the rods had allowed recurrence of the deformity; and in four, the short limb of one or both of the L-shaped rods had rotated out of the pelvis and perforated the skin, resulting in an infection that necessitated removal of the rods. At the time of the review, the deformity was essentially the same as before the original instrumentation in all but the sixteenth patient, in whom failure had not occurred. The instrumented vertebrae had grown measurably in some of the patients, but spontaneous fusion--particularly in the thoracic spine--was observed when the rods were removed. This finding indicates that, using presently available materials, segmental instrumentation of the spine without arthrodesis does not effectively control paralytic scoliosis secondary to poliomyelitis in a growing child.

Treatment of intracapsular hip fractures by the Deyerle method. A comparative review of one hundred and nineteen cases.

In a retrospective review of 119 intracapsular hip fractures treated by the Deyerle method (seventy-nine patients treated at San Francisco General Hospital and forty at Brookside Community Hospital), fifty-nine patients were available for follow-up after two or more years or were rated as failures before that time. In the San Francisco General series the incidence of avascular necrosis was 43 per cent and of non-union, 23 per cent, while in the Brookside series the incidences were 12.5 per cent and 12.5 per cent, respectively. The functional end results in the San Francisco General series were rated excellent or satisfactory in 40 per cent and failures in 60 per cent, and in the Brookside series there were 75 per cent excellent or satisfactory results and 25 per cent failures.

[Computed tomography of intra-articular calcaneal fractures]. / Computertomographie intraartikulärer Kalkaneusfrakturen.

The increasing number of operations on intraarticular calcaneal fractures created the need for a fast, reproducible method to examine the weight-bearing posterior talo-calcaneal joint. High resolution CT scanning in an almost coronal plane without reformating was done in 25 calcaneal fractures. Joint alignment and fragment dislocation were demonstrated more precisely than would have been possible with conventional studies. Three typical fractures were found: The lambda type, the y type and the comminution type. Follow-up studies showed osteo-arthritis, intraarticular degenerative changes of the articular surface and impingement of personeal tendons as possible causes of pain.

Glucagon-producing neuroendocrine tumour associated with hypoaminoacidaemia and skin lesions.

A nine-year-old neutered female crossbred Bernese mountain dog was diagnosed with superficial necrolytic dermatitis and a glucagon-producing islet cell tumour. Laboratory findings included hyperglucagonaemia and hypoaminoacidaemia. The dog was euthanased because of progression of the disease, and necropsy revealed liver metastases of a neuroendocrine carcinoma with immunohistochemical expression of glucagon and somatostatin. This report represents a case of canine glucagonoma syndrome; the previously reported cases in dogs are also briefly described.

[The Gamma Nail in per- and intertrochanteric femoral fractures--alternative or supplement to the dynamic hip screw? A prospective randomized study of 100 patients with per- and intertrochanteric femoral fractures in the surgical clinic of the City Hospital of Triemli, Zurich, September 1989 - June 1990]. / Der Gamma-Nagel bei per- und intertrochantären Femurfrakturen--Alternative oder Ergänzung zur DHS? Eine prospektive randomisierte Studie anhand von 100 Patienten mit per- und intertrochantären Femurfrakturen an der Chirurgischen Klinik des Stadtspitals Triemli, Zürich, September 1989-Juni 1990.

In a prospective randomised trial between September 89 and June 90 one hundred patients with per- and subtrochanteric fractures were consecutively treated by Gamma-nail or DHS. The average age of both groups was about 80 years. The operation time for Gamma-nailing was longer than for DHS-implantation and also the postoperative blood loss was higher in the Gamma-nail-group. We found no difference of intraoperative blood loss, of perioperative letality and in duration of hospital care. 90% of Gamma-nail-patients and 80% of DHS-patients were successfully able to walk four days after operation with full weight bearing on the operated limb. Six patients (12%) with DHS had to be reoperated within 6 weeks. Three patients with unstable fractures got cranial perforation of the cephalic screw after mobilisation. The other three patients had soft tissue complications. Five patients (10%) of the Gamma-nail-group were reoperated, one case because of missed distal locking, one because of cranial perforation of the cephalic screw after varus dislocation of the proximal fragment. One patient suffered intraoperatively a proximal femur shaft fracture which was corrected during operation. In one case a wound hematoma was evacuated, an other patient needed secondary wound closure. Despite technical imperfection of implant and instruments, we conclude that the Gamma-nail allows a very high percentage early and full weight bearing immediately after operation. So we consider that in the treatment of unstable pertrochanteric fractures of geriatric patients, the Gamma-nail has proven to be more efficient than the DHS.

CD4+ immune response as a potential biomarker of patient reported inflammatory bowel disease (IBD) activity.

BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBDs) which are characterized by dysfunctional regulation of the immune system. A number of immune modifying drugs are used to treat CD and UC. Therapy is adjusted largely on the bases of subjective reports of disease activity and non-specific laboratory tests. Identification of a single or combination of immune markers of disease activity could be useful to select and monitor therapeutic responses. However, to date no reliable quantitative associations between IBD activity and laboratory measures of immune function have been identified. This study was designed to evaluate the usefulness of a commercially available laboratory measure of CD4(+) immune function, the Cylex® ImmuKnow®, as a surrogate marker of IBD activity. METHODS: Adult IBD patients with either CD (N=55, 27 males, mean, SD age=38.5, 11.5 years) or UC (N=45, 24 males, mean, SD age=41.7, 15.4 years) were enrolled. Patients both in clinical remission and with active disease provided responses to structured, validated questionnaires (CDAI and HBI for CD patients and SCCAI for UC patients) used to monitor IBD activity. Whole blood and plasma samples were collected to quantify various markers of disease status including routine cell counts and differentials (CBCs), CRP, and albumin (Alb), as well as CD4(+) immune response (Cylex® ImmuKnow®, N=98). Results were compared between all IBD patients as well as between CD and UC subgroups. RESULTS: There was a good correlation between the results of CDAI and HBI scores (r=0.811, p<0.01, Spearman-Rho) but HBI scores correlated slightly better (r=0.575, p<0.001) than the CDAI's (r=0.449, p=0.001) with CD patients' reported perception of their general condition. CDAI and HBI scores categorized 12/55 versus 36/55 of CD patients respectively as having active disease. SCCAI scores indicated that 25/45 of UC patients had active disease. Cylex® results (in ng/mL of ATP) were increased in 74/98 IBD subjects (≥525 ng/mL) but were influenced by the use of systemic corticosteroids (SCS) and infliximab. There were weak but statistically significant Spearman-Rho correlations between Alb concentrations and both CDAI (r=0.413, p=0.002) and HBI (r=0.325, p=0.017) scores as well as between CRP values and HBI scores (r=0.331, p=0.016). Correlations between CRP and both CDAI and SCCAI scores and between Alb and SCCAI scores were not significant and there were no significant positive associations between any of the three clinical scores and Cylex® results. CONCLUSIONS: CD4(+) immune responses were significantly elevated in IBD patients whether or not they were in clinical remission but were influenced by treatment. There were some significant correlations between the clinical scores and CRP or Alb but not with the CD4(+) results. Both other clinical scoring systems, other measures of immune function, and CD4(+) immune response changes over time should be examined to see if this or other laboratory measures of immune response are predictive of actual disease activity or symptoms in CD or UC patients.

[Hook plate (so-called Balser plate) or tension banding with the Bosworth screw in complete acromioclavicular dislocation and clavicular fracture]. / Hakenplatte (sog. Balserplatte) oder Zuggurtung mit Bosworth-Schraube bei vollständiger Acromio-clavicular-Luxation und lateraler Claviculafraktur.

With both treatments good results are achieved. In cases treated with the hook-plate mobilisation and load putting are earlier possible. These patients are sooner back to work. The costs for the hook-plate are higher. To take out the hook-plate a second hospitalisation is necessary.

[Long-term follow-up of surgically treated intra-articular calcaneus fractures]. / Langzeitnachkontrolle operierter intraartikulärer Kalkaneusfrakturen.

Between 1980 and 1991 we treated 150 joint fractures of the os calcis with open reduction and internal fixation with a special AO-plate. In this report we show the results of 36 fractures in 33 patients after an average follow-up of 89 months (43-132). Patients got back their working ability between 4.6 and 5.6 months. At the time of the clinical control two third of the patients had a working ability of 100%. 4 patients changed their profession due to the poor result of the fracture. 12% of the cases ended in spontaneous or secondary arthrodesis of the lower ankle joint. One third of the patients need orthopedic supports or special shoes. 73% of the patients are satisfied with the result.

[Quality control after hernia operation]. / Qualitätskontrolle nach Hernienoperationen.

QUESTION: An important feature in surgery is the absence of wound infection after elective sterile operation. That's why the VQG (Verein zur Qualitätssicherung im Gesundheitswesen) from Berne recommends as a standard control the surveillance of wound healing, where hernia repair is suited for a tracer operation [1]. METHOD: In our hospital retrospectively all 106 patients of the year 1999 were asked by a questionnaire, 3 month after operation, if their wound healed primarily or if they noticed any signs of infection or even had to be re-operated again. RESULTS: Most hernias were indirect (71) or direct (11), followed by umbilical hernias (11), epigastric or incisional hernias (4), femoral hernias (2). The majority of procedures were a Shouldice repair (43), followed by mesh implantation according to Lichtenstein (33) or Bassini repair (15). 14 times an umbilical or epigastric hernia was operated by Mayo's method. One Stoppa operation was performed. 7 Hernias were incarcerated at the time of operation. 51 hernias were on the right, 41 on the left side, 5 on both sides. Mean age of patients was 52.9 years; mean duration of hospital stay was 4.42 days. After Shouldice repair hospital stay was 3.9 days with an average patients age of 48.3 years, after Bassini 5.41 days (mean age 46.4 years), after Lichtenstein repair 5.23 days (mean age 66.0 years). 82 (77.4%) from 106 patients returned the questionnaire. 67 (81.7%) were completely satisfied, 11 (13.6%) mentioned minor problems. So 95.1% had a normal primary wound healing without infection. There was no correlation between wound healing, type of hernia, age, hospital stay, surgeon or method of operation. In the same study other complications occurred (e.g. 5% recurrences of hernias, nerve lesions), that could not be integrated into the evaluation because they were excluded by definition. CONCLUSION: Studying the tracer "wound healing after groin hernia repair" allows an approximate follow-up for quality control with little expense. Because of the narrow point of view and the neglect of other complications in the same investigation we estimate the power of the result as limited.

[The gamma-nail as a resilient alternative to the dynamic hip screw in unstable proximal femoral fractures in the elderly]. / Der Gamma-Nagel als belastungsstabile Alternative zur DHS bei der instabilen proximalen Femurfraktur des alten Menschen.

In a prospective randomised trial between September 1989 and June 1990 one hundred patients with per- and subtrochanteric fractures were consecutively treated by gamma-nail or DHS. The average age of both groups was about 80 years. The operation time for gamma-nailing was longer than for DHS implantation and also the postoperative blood loss was higher in the gamma-nail group. We found no difference of intraoperative blood loss, of perioperative lethality and in duration of hospital care. 90% of gamma-nail patients and 80% of DHS patients were successfully able to walk four days after operation with full weight bearing on the operated limb. Three patients in the DHS group with unstable fractures got cranial perforation of the cephalic screw mobilisation. Five patients of the gamma-nail group were reoperated, one case because of missed distal locking, one because of cranial perforation of the cephalic screw after varus dislocation of the proximal fragment. One patient suffered intraoperatively a proximal femur shaft fracture which was corrected during operation. In one case a wound hematoma was evacuated, an other patient needed secondary wound closure. Despite technical imperfection of implant and instruments, we conclude that the gamma-nail allows a very high percentage early and full weight bearing immediately after operation. So we consider that in the treatment of unstable pertrochanteric fractures of geriatric patients, the gamma-nail has proven to be more efficient than the DHS.

Relative trochanteric overgrowth after ischemic necrosis in congenital dislocation of the hip.

To determine the relative trochanteric overgrowth after ischemic necrosis of the femoral head during treatment of congenital dislocation of the hip (CDH), we reviewed radiographs of patients with ischemic necrosis and no femoral side surgery. The articulotrochanteric distance (ATD) was recorded after physeal closure. Ischemic necrosis was classified with the systems proposed by Salter et al. and Kalamchi and MacEwen. The resultant overgrowth was correlated with these systems. The articulotrochanteric distance in 29 patients with a Trendelenburg gait was also measured. The Kalamchi classification is more useful for predicting relative trochanteric overgrowth. Children with an ATD of less than or equal to 0 mm are likely to have a Trendelenburg gait.

[The gamma nail--an ideal implant for treatment of unstable fractures in elderly patients]. / Der Gamma-Nagel--ein ideales Implantat zur Behandlung instabiler Frakturen bei alten Patienten.

Altogether we used the Gamma-Nail in 150 cases. We show here a series of 50 instable pertrochanteric femur fractures in very old patients which we treated with a Gamma-Nail. All cases started with full weight bearing at the 4th day after operation. A clinical and radiological control 12 weeks later shows good mobilisation of the hip in 70% of the cases. Shortening of the operated leg is rare in comparison of cases treated with a DHS. Two thirds of the patients returned after dismission of the hospital to the old social situation. The advantages in treating instable pertrochanteric femur fractures with the Gamma-Nail are immediate full weight bearing without risks of shortening of the operated leg and the closed reduction of the fracture.