An optically multiplexed single-shot time-resolved probe of laser-plasma dynamics.

We introduce a new approach to temporally resolve ultrafast micron-scale processes via the use of a multi-channel optical probe. We demonstrate that this technique enables highly precise time-resolved, two-dimensional spatial imaging of intense laser pulse propagation dynamics, plasma formation and laser beam filamentation within a single pulse over four distinct time frames. The design, development and optimization of the optical probe system is presented, as are representative experimental results from the first implementation of the multi-channel probe with a high-power laser pulse interaction with a helium gas jet target.

Hot-spot mix in ignition-scale inertial confinement fusion targets.

Mixing of plastic ablator material, doped with Cu and Ge dopants, deep into the hot spot of ignition-scale inertial confinement fusion implosions by hydrodynamic instabilities is diagnosed with x-ray spectroscopy on the National Ignition Facility. The amount of hot-spot mix mass is determined from the absolute brightness of the emergent Cu and Ge K-shell emission. The Cu and Ge dopants placed at different radial locations in the plastic ablator show the ablation-front hydrodynamic instability is primarily responsible for hot-spot mix. Low neutron yields and hot-spot mix mass between 34(-13,+50) ng and 4000(-2970,+17 160) ng are observed.

Precision shock tuning on the national ignition facility.

Ignition implosions on the National Ignition Facility [J. D. Lindl et al., Phys. Plasmas 11, 339 (2004)] are underway with the goal of compressing deuterium-tritium fuel to a sufficiently high areal density (ρR) to sustain a self-propagating burn wave required for fusion power gain greater than unity. These implosions are driven with a very carefully tailored sequence of four shock waves that must be timed to very high precision to keep the fuel entropy and adiabat low and ρR high. The first series of precision tuning experiments on the National Ignition Facility, which use optical diagnostics to directly measure the strength and timing of all four shocks inside a hohlraum-driven, cryogenic liquid-deuterium-filled capsule interior have now been performed. The results of these experiments are presented demonstrating a significant decrease in adiabat over previously untuned implosions. The impact of the improved shock timing is confirmed in related deuterium-tritium layered capsule implosions, which show the highest fuel compression (ρR~1.0 g/cm(2)) measured to date, exceeding the previous record [V. Goncharov et al., Phys. Rev. Lett. 104, 165001 (2010)] by more than a factor of 3. The experiments also clearly reveal an issue with the 4th shock velocity, which is observed to be 20% slower than predictions from numerical simulation.

Assembly of high-areal-density deuterium-tritium fuel from indirectly driven cryogenic implosions.

The National Ignition Facility has been used to compress deuterium-tritium to an average areal density of ~1.0±0.1 g cm(-2), which is 67% of the ignition requirement. These conditions were obtained using 192 laser beams with total energy of 1-1.6 MJ and peak power up to 420 TW to create a hohlraum drive with a shaped power profile, peaking at a soft x-ray radiation temperature of 275-300 eV. This pulse delivered a series of shocks that compressed a capsule containing cryogenic deuterium-tritium to a radius of 25-35 µm. Neutron images of the implosion were used to estimate a fuel density of 500-800 g cm(-3).

Validity of a low-cost Lichtenstein open inguinal hernia repair simulation model for surgical training.

PURPOSE: Simulation training allows trainees to gain experience in a safe environment. Computer simulation and animal models to practice a Lichtenstein open inguinal hernia repair (LOIHR) are available; however, a low-cost model is not. We constructed an inexpensive model using fabric, felt, and yarn that simulates the anatomy and hazards of the LOIHR. This study examined the fidelity, and perceived usefulness of our developed simulation model by surgical residents and expert surgeons. METHODS: A total of 66 Dutch surgical residents and ten international expert surgeons were included. All participants viewed a video-demonstration of LOIHR on the simulation model and subsequently performed the surgery themselves on the model. Afterward, they assessed the model by rating 13 statements concerning its fidelity (six model, three equipment, and four psychological) and six usefulness statements on a five-point Likert scale. One-sample Wilcoxon signed-rank test was used to compare to the neutral value of 3. RESULTS: The fidelity was assessed as being high by residents [model 4.00 (3.00-4.00), equipment 4.00 (3.00-4.00), psychological 4.00 (3.00-4.00); all p's < 0.001] and by expert surgeons [model 4.00 (3.00-4.00), p = 0.025; equipment 4.00 (3.00-5.00), p < 0.001; psychological 4.00 (3.00-4.00), p = 0.053]. The usefulness was rated high by residents and experts, especially the usefulness for training of residents [residents 4.00 (4.00-5.00), p < 0.001; experts 4.50 (3.75-5.00), p = 0.015]. CONCLUSION: Our developed Lichtenstein open inguinal hernia repair simulation model was assessed by surgical residents and expert surgeons as a model with high fidelity and high potential usefulness, especially for the training of surgical residents.

Effect of plastic coating on the density of plasma formed in Si foil targets irradiated by ultra-high-contrast relativistic laser pulses.

The formation of high energy density matter occurs in inertial confinement fusion, astrophysical, and geophysical systems. In this context, it is important to couple as much energy as possible into a target while maintaining high density. A recent experimental campaign, using buried layer (or "sandwich" type) targets and the ultrahigh laser contrast Vulcan petawatt laser facility, resulted in 500 Mbar pressures in solid density plasmas (which corresponds to about 4.6×10^{7}J/cm^{3} energy density). The densities and temperatures of the generated plasma were measured based on the analysis of x-ray spectral line profiles and relative intensities.

Metastatic malignant melanoma.

Metastatic malignant melanoma is an incurable malignancy with extremely poor prognosis. Patients bearing this diagnosis face a median survival time of approximately 9 months with a probability of surviving 5 years after initial presentation at less than 5%. This is contrasted by the curative nature of surgical resection of early melanoma detected in the skin. To date, no systemic therapy has consistently and predictably impacted the overall survival of patients with metastatic melanoma. However, in recent years, a resurgence of innovative diagnostic and therapeutic developments have broadened our understanding of the natural history of melanoma and identified rational therapeutic targets/strategies that seem poised to significantly change the clinical outcomes in these patients. Herein we review the state-of-the-art in metastatic melanoma diagnostics and therapeutics with particular emphasis on multi-disciplinary clinical management.

Surgical trends of groin hernia repairs performed for recurrence in medicare patients.

BACKGROUND: The recurrence rate after groin hernia repair (GHR) has been estimated to be between 1-10% in adult patients. Neither national rates nor trends in recurrence over time have been reliably established for Medicare patients in the USA. MATERIALS: We evaluated patients undergoing GHR (inguinal = IHR; femoral = FHR) from 2011 to 2014 from the Medicare Provider Analysis and Review database. Patients were identified using ICD-9 diagnosis and ICD-9 and CPT procedure codes, stratified both by primary vs. recurrent hernia repair and by sex. One-tailed Cochran-Armitage tests evaluated trends over time and a generalized estimating equation model estimated factors associated with recurrent IHR or FHR. RESULTS: We identified 407,717 patients (87.0%, ≥ 65 years) who underwent an IHR and 11,578 (91.0%, ≥ 65 years) who underwent a FHR. The proportion of IHRs for recurrence decreased statistically from 14.3% in 2011 to 13.9% in 2014 (p < 0.01) in males and was increased, but not statistically so (7.0-7.4%) in females (p = 0.08). The proportion of FHRs for recurrence was decreased, but not statistically so (16.3-14.8%, p = 0.29) in males and increased in females (5.3-6.3%, p = 0.02). On multivariable analysis, males were more than twice as likely as females to undergo recurrent repair (IHR or FHR, both p < 0.01). CONCLUSIONS: Within the Medicare population, recurrence rates after groin hernia repairs were found to be higher than previously reported but have remained clinically stable over time. Establishing and reducing this rate is important for patient outcomes and expectations.

Consequences of endoscopic inguinal hernioplasty with mesh on subsequent open radical prostatectomy.

AIM: To determine the effect of prior endoscopic hernia repair with prosthetic mesh on subsequent open radical prostatectomy. METHODS: A retrospective study from 1990 to 2004 identified nine patients with preperitoneal mesh placement followed by open radical prostatectomy. Case controls (n = 26) were matched for age, type of operation, year of surgery and pathologic stage of prostatic adenocarcinoma. Outcome variables of operating time, number of pelvic lymph nodes excised, duration of hospital stay, duration of urinary catheterization, recurrence rates, and incidence of complications were compared. Data analysis was performed using Wilcoxon's rank sums test. RESULTS: Intraoperatively, subjective difficulty in dissection was documented in all cases by the performing urologist. Duration of hospital stay was significantly increased by 1.3 days (p < 0.05), as compared to the control group. However, no statistically significant increase in mean operating time (173 vs. 172 min, p = 0.925), number of lymph nodes sampled (4.4 vs. 6.6, p = 0.147), duration of urinary catheterization (22 vs. 19 days, p = 0.925), oncologic recurrence (11 vs. 11% at 6.1 and 4.8 years follow-up), or complications was found. CONCLUSIONS: Prior TEP/TAPP did not increase the morbidity or mortality of subsequent prostate surgery. Despite some subjective operative difficulty, open prostatectomy was safe and feasible in all cases with a comparable oncologic outcome. Mesh-associated inflammation may preclude adequate nodal sampling. While endoscopic hernia repair remains an excellent option to fix unilateral, bilateral, and recurrent herniae, consideration of future prostate surgery is important. Inserting less "inflammatory" mesh or using an open, anterior approach may be prudent in some men at high risk for needing subsequent prostate surgery.

Postoperative hematoma following inguinal herniorrhaphy: patient characteristics leading to increased risk.

BACKGROUND: Although relatively infrequent, groin hematoma following inguinal herniorrhaphy is a morbid complication with major ramifications of mesh infection and hernia recurrence. We have sensed an increasing frequency of this complication in our tertiary referral practice and sought to determine whether or not significant risk factors could be identified. METHODS: In this matched case-control study (1995-2003), we identified 53 patients with groin hematomas and paired them with 106 age- and gender-matched controls. Patient and procedure characteristics were analyzed using chi-square and both univariate and multivariable, conditional logistic regression analysis. RESULTS: The 53 patients developing groin hematoma following inguinal hernia repair (mean age=65, range 22-87, 90% male) were well matched with 106 controls (mean age=65, range 22-87, 90% male). There was no significant difference in the location (left, right, bilateral), type (direct, indirect, pantaloon, first repair, or recurrent), or technique of hernia repair (Bassini, Lichtenstein, mesh plug, endoscopic, or McVay) between groups. While univariate analysis identified Coumadin usage (P<0.001, hazard ratio 19.1), valvular disease (P<0.001, hazard ratio 10.9), atrial fibrillation (P=0.02, hazard ratio 4.2), vascular disease (P=0.04, hazard ratio 2.2), blood abnormalities (P=0.02, hazard ratio 3.2), and previous bleeding episodes (P=0.02, hazard ratio 4.9) as significant factors, only preoperative Coumadin usage was important in multivariate analysis. CONCLUSION: The crucial risk factor for groin hematoma developing in patients undergoing inguinal hernia repair is preoperative need for Coumadin therapy. Although the perioperative management of anticoagulation in patients undergoing inguinal herniorrhaphy is not clearly defined, meticulous management of patients requiring Coumadin therapy seems prudent.

Proportion of femoral hernia repairs performed for recurrence in the United States.

PURPOSE: Recurrence rates after femoral hernia repair (FHR) have not been reliably established in the USA. We sought to determine this trend over time. METHODS: The proportion of primary and recurrent FHRs was determined for patients age ≥ 18 from: ACS-NSQIP (1/2005-12/2014), Premier (1/2010-09/2015), and institutional (1/2005-12/2014) data. Trends were analyzed using a one-tailed Cochran-Armitage test. RESULTS: In the NSQIP database, 6649 patients underwent a FHR. In females, the proportion of FHRs performed for recurrence decreased from 14.0% in 2005 to 6.2% in 2014, p = 0.02. In males, there was no change: 16.7-16.1% 2005-2014 (p = 0.18). The Premier database included 4495 FHRs and our institution 315 FHRs. There was no difference for either gender over time in either data source, all p > 0.05. CONCLUSIONS: The proportion of femoral hernia repairs performed for recurrence in the USA remained relatively constant in males in two large national databases between 2005 and 2015. In females, a decrease was seen in one of the large national databases.

Enhancing titres of therapeutic viral vectors using the transgene repression in vector production (TRiP) system.

A key challenge in the field of therapeutic viral vector/vaccine manufacturing is maximizing production. For most vector platforms, the 'benchmark' vector titres are achieved with inert reporter genes. However, expression of therapeutic transgenes can often adversely affect vector titres due to biological effects on cell metabolism and/or on the vector virion itself. Here, we exemplify the novel 'Transgene Repression In vector Production' (TRiP) system for the production of both RNA- and DNA-based viral vectors. The TRiP system utilizes a translational block of one or more transgenes by employing the bacterial tryptophan RNA-binding attenuation protein (TRAP), which binds its target RNA sequence close to the transgene initiation codon. We report enhancement of titres of lentiviral vectors expressing Cyclo-oxygenase-2 by 600-fold, and adenoviral vectors expressing the pro-apoptotic gene Bax by >150,000-fold. The TRiP system is transgene-independent and will be a particularly useful platform in the clinical development of viral vectors expressing problematic transgenes.

The osteoclast-associated protease cathepsin K is expressed in human breast carcinoma.

Human cathepsin K is a novel cysteine protease previously reported to be restricted in its expression to osteoclasts. Immunolocalization of cathepsin K in breast tumor bone metastases revealed that the invading breast cancer cells expressed this protease, albeit at a lower intensity than in osteoclasts. In situ hybridization and immunolocalization studies were subsequently conducted to demonstrate cathepsin K mRNA and protein expression in samples of primary breast carcinoma. Expression of cathepsin K mRNA was confirmed by reverse transcription PCR and Southern analysis in a number of human breast cancer cell lines and in primary human breast tumors and their metastases. As this protease is known to degrade extracellular matrix, including bone matrix proteins, it is possible that cathepsin K may contribute to the invasive potential of breast cancer cells, including those that metastasize to bone. Thus, cathepsin K may be a potential target leading to the design of novel drugs for cancer therapy.

TEP and Lichtenstein anatomy: does simulation accelerate acquisition among interns?

PURPOSE: The anatomy of the inguinal region is notoriously challenging to master. We sought to teach open inguinal hernia (OIH) and totally extraperitoneal (TEP) anatomy with simulation models among general surgery (GS) interns. METHODS: Low-fidelity OIH and TEP models were constructed out of cardboard, plastic bins, fabric, and yarn. GS interns (n = 30) participated in a 3-h hernia session including a pretest, anatomy lecture, simulated OIH and TEP hernia repair, and posttest. Pre- and posttest scores were based on a difficult 30-point exam which included didactic questions (10 points), drawing relevant TEP (10 points), and OIH (10 points) anatomy. Participants were surveyed following the session. RESULTS: Median pretest scores were 13 % (range 0-60 %). Median posttest scores improved to 47 % (range 20-93 %, p < 0.001). Median number of structures drawn in the TEP image improved from 2 (range 0-14) to 11 (range 1-21, p < 0.001). Median number of structures drawn in the OIH image improved from 3 (range 0-15) to 7 (range 1-19, p < 0.001). 67 % (12/18) demonstrated improvement in knowledge of abdominal wall layers. 23 % (7/30) knew the triangles of pain/doom on the pretest vs. 77 % (23/30) on the posttest. Mean Likert scores favored session enjoyability (4.5), not a waste of training time (4.4), and improved understanding of OIH and TEP anatomy (4.4, 4.2). CONCLUSIONS: Low-fidelity simulators can be used to teach and assess knowledge of TEP and OIH anatomy. While enjoyable and useful, one 3-h session does not create master hernia surgeons or expert anatomists out of novice trainees.

Cloning and sequence analysis of rat hepsin, a cell surface serine proteinase.

A cDNA coding for the rat serine proteinase hepsin was isolated and its nucleotide sequence has been determined. The cDNA was 1739 nucleotides long and contained an open reading frame encoding a protein consisting of 416 amino-acid residues. The deduced amino-acid sequence of the rat enzyme was very similar to the human hepsin sharing an amino-acid sequence identity of 88.7%. Hydropathy plots reveal the presence of a short hydrophobic region close to the N-terminus believed to be a transmembrane domain which anchors the proteinase on the cell surface. The predicted sequence contains the His, Asp and Ser residues which make up the catalytic triad common to all serine proteinases.

Sentinel lymph node biopsy with metastasis: can axillary dissection be avoided in some patients with breast cancer?

PURPOSE: Recent studies have suggested that the sentinel lymph node (SLN) biopsy is an accurate alternative staging procedure for women with breast cancer. The goal of this study was to identify a subset of breast cancer patients in whom metastatic disease was confined only to the SLN. MATERIALS AND METHODS: From two institutions, we recruited 222 women with breast cancer for SLN biopsy. A SLN biopsy was performed in each patient, followed by an axillary dissection in 182 patients. Histologic and immunohistochemical cytokeratin stains were used on all SLNs. RESULTS: The SLN was identified in 220 (97. 8%) of the 225 biopsies. Evidence of metastatic breast cancer in the SLN was found in 60 (27.0%) of the 222 patients. Of these patients, 32 (53.3%) had evidence of tumor in the SLN only. By multivariate analysis, two factors were found to be significantly associated with a higher likelihood of tumor involvement in the non-SLNs: primary tumor size larger than 2.0 cm (P =.0004) and macrometastasis (> 2.0 mm) in the SLN (P =.002). Additional analysis revealed that none (0%; 95% confidence interval, 0% to 18.5%) of the 18 patients with primary tumors < or = 2.0 cm and micrometastasis to the SLN had remaining axillary lymph node involvement. CONCLUSION: The primary tumor size and metastasis size in the SLN are independent factors in predicting the incidence of tumor in the non-SLNs. Therefore, the SLN biopsy alone may be adequate for staging and/or therapy decision making in patients with primary breast tumors < or = 2.0 cm and micrometastasis in the SLN.

Uterine catecholamines and prostaglandins during the estrous cycle of the rat.

The uterine contents of norepinephrine, epinephrine, dopamine, and prostaglandins F and E were determined on each day of the rat estrous cycle. Catecholamines were determined by high performance liquid chromatography with electrochemical detection (HPLC-EC) as well as by a radioenzymatic technique; prostaglandins were quantitated by RIA. The norepinephrine and dopamine values obtained by the radioenzymatic assay were approximately 1.5 times as high as the values obtained by HPLC-EC (norepinephrine, 285 vs. 188 ng/g; dopamine, 11.0 vs. 7.5 ng/g). Despite this difference in levels, both analytic techniques showed a decline in uterine norepinephrine from diestrus to estrus, followed by a significant (P less than 0.01) increase in norepinephrine on the day of metestrus. A cyclic pattern was also revealed for uterine dopamine concentration. There was a decline in dopamine concentration from diestrus to proestrus (radioenzymatic, P less than 0.01), followed by a return to high levels at metestrus (HPLC-EC). Epinephrine levels were low (undetectable by radioenzymatic assay; 24 ng/g by HPLC-EC) and showed no variation during the estrous cycle. Prostaglandin F was uniformly higher than prostaglandin E (10 vs. 2.5 ng/uterus). Significant increases in the uterine contents of both prostaglandins were shown on the day of proestrus.

Renal substance P-containing neurons and substance P receptors impaired in hypertension.

In normotensive rats, increased renal pelvic pressure stimulates the release of prostaglandin E and substance P, which in turn leads to an increase in afferent renal nerve activity (ARNA) and a contralateral natriuresis, a contralateral inhibitory renorenal reflex. In spontaneously hypertensive rats (SHR), increasing renal pelvic pressure failed to increase afferent renal nerve activity. The inhibitory nature of renorenal reflexes indicates that impaired renorenal reflexes could contribute to increased sodium retention in SHR. Phorbol esters, known to activate protein kinase C, increase afferent renal nerve activity in Wistar-Kyoto rats (WKY) but not in SHR. We examined the mechanisms involved in the impaired responses to renal sensory receptor activation in SHR. The phorbol ester 4beta-phorbol 12,13-dibutyrate increased renal pelvic protein kinase C activity similarly in SHR and WKY. Increasing renal pelvic pressure increased afferent renal nerve activity in WKY (27+/-2%) but not in SHR. Renal pelvic release of prostaglandin E increased similarly in WKY and SHR, from 0.8+/-0.1 to 2.0+/-0.4 ng/min and 0.7+/-0.1 to 1.4+/-0.2 ng/min. Renal pelvic release of substance P was greater (P<.01) in WKY, from 16.3+/-3.8 to 41.8+/-7.4 pg/min, than in SHR, from 9.9+/-1.7 to 17.0+/-3.2 pg/min. In WKY, renal pelvic administration of substance P at 0.8, 4, and 20 microg/mL increased ARNA 382+/-69, 750+/-233, and 783+/-124% second (area under the curve of afferent renal nerve activity versus time). In SHR, substance P at 0.8 to 20 microg/mL failed to increase ARNA. These findings demonstrate that the impaired afferent renal nerve activity response to increased renal pelvic pressure is related to decreased release of substance P and/or impaired activation of substance P receptors.

Laparoscopic adrenalectomy for adrenocorticotropin-dependent Cushing's syndrome.

Bilateral adrenalectomy is indicated for the treatment of ACTH-dependent Cushing's syndrome when the tumorous source of ACTH hypersecretion cannot be identified or removed. Potential advantages of laparoscopic over open adrenalectomy include shorter hospitalization, decreased requirement for postoperative analgesia, and decreased postoperative morbidity due to incisional complications. Bilateral laparoscopic adrenalectomy performed for the treatment of ACTH-dependent Cushing's syndrome was attempted in 19 patients at our institution between 1995 and 1998. Conversion to an open procedure was required in three patients. All patients who underwent bilateral laparoscopic adrenalectomy were subsequently followed to assess the outcome of this intervention. Twelve patients with pituitary-dependent Cushing's syndrome and four with ectopic ACTH syndrome underwent successful bilateral laparoscopic adrenalectomy. All patients experienced resolution of the signs and symptoms (e.g. proximal myopathy, hirsutism, and emotional lability) of Cushing's syndrome as well as weight loss, improved glucose tolerance, and improved control of blood pressure. No residual cortisol secretion was detected in the patients. Bilateral laparoscopic adrenalectomy is a safe and effective treatment for Cushing's syndrome when the ACTH-secreting neoplasm cannot be removed.

Paget's disease of the breast.

Paget's disease of the breast is a rare disorder of the nipple-areola complex that is often associated with an underlying in situ or invasive carcinoma. A change in sensation of the nipple-areola, such as itching and burning, is a common presenting symptom. Objectively, eczematoid changes of the nipple-areola complex are common. The later stages of Paget's disease of the breast are characterized by ulceration and destruction of the nipple-areola complex. Eczematoid changes of the nipple-areola complex and persisting soreness or itching, without obvious reason, is a suspicious symptom for Paget's disease of the breast and calls for thorough evaluation, including mammography. Exfoliative cytology with demonstration of Paget's cells may be useful, but a negative finding does not exclude Paget's disease of the breast. Surgical biopsy is the diagnostic standard and therefore the diagnosis should always be confirmed by open (surgical) biopsy. The histogenesis of Paget's disease of the breast continues to be debated. The epidermotropic theory holds that Paget's cells are ductal carcinoma cells that have migrated from the underlying breast parenchyma to the nipple epidermis. According to the in situ transformation theory, the Paget's cells arise as malignant cells in the nipple epidermis independent from any other pathologic process within the breast parenchyma. This theory has been proposed to explain those cases in which there is no underlying mammary carcinoma or when there is a carcinoma remote from the nipple-areola complex. Each of these theories is plausible; however, treatment approaches differ markedly depending on the theory of histogenesis. Mastectomy has been considered the standard of care in the management of patients with Paget's disease of the breast. Nowadays, however, some patients with Paget's disease of the breast are candidates for breast-conserving therapy. Patients must be selected carefully on an individual basis. Until there is a better understanding of the relationship of Paget's disease of the breast to the underlying cancer the surgeon should understand the natural history and behaviour of this lesion and be aware of both the risks of under- and over-treating patients with Paget's disease of the breast.