Engineering of light confinement in strongly scattering disordered media.

Disordered photonic materials can diffuse and localize light through random multiple scattering, offering opportunities to study mesoscopic phenomena, control light-matter interactions, and provide new strategies for photonic applications. Light transport in such media is governed by photonic modes characterized by resonances with finite spectral width and spatial extent. Considerable steps have been made recently towards control over the transport using wavefront shaping techniques. The selective engineering of individual modes, however, has been addressed only theoretically. Here, we experimentally demonstrate the possibility to engineer the confinement and the mutual interaction of modes in a two-dimensional disordered photonic structure. The strong light confinement is achieved at the fabrication stage by an optimization of the structure, and an accurate and local tuning of the mode resonance frequencies is achieved via post-fabrication processes. To show the versatility of our technique, we selectively control the detuning between overlapping localized modes and observe both frequency crossing and anti-crossing behaviours, thereby paving the way for the creation of open transmission channels in strongly scattering media.

A Lévy flight for light.

A random walk is a stochastic process in which particles or waves travel along random trajectories. The first application of a random walk was in the description of particle motion in a fluid (brownian motion); now it is a central concept in statistical physics, describing transport phenomena such as heat, sound and light diffusion. Lévy flights are a particular class of generalized random walk in which the step lengths during the walk are described by a 'heavy-tailed' probability distribution. They can describe all stochastic processes that are scale invariant. Lévy flights have accordingly turned out to be applicable to a diverse range of fields, describing animal foraging patterns, the distribution of human travel and even some aspects of earthquake behaviour. Transport based on Lévy flights has been extensively studied numerically, but experimental work has been limited and, to date, it has not seemed possible to observe and study Lévy transport in actual materials. For example, experimental work on heat, sound, and light diffusion is generally limited to normal, brownian, diffusion. Here we show that it is possible to engineer an optical material in which light waves perform a Lévy flight. The key parameters that determine the transport behaviour can be easily tuned, making this an ideal experimental system in which to study Lévy flights in a controlled way. The development of a material in which the diffusive transport of light is governed by Lévy statistics might even permit the development of new optical functionalities that go beyond normal light diffusion.

Incidence, risk profile and morphological pattern of lower extremity venous thromboembolism after urological cancer surgery.

PURPOSE: We examined the incidence of asymptomatic and symptomatic lower extremity venous thromboembolism in patients who underwent urological surgery for cancer, and identified preoperative and operative risk factors predictive of the thromboembolism. MATERIALS AND METHODS: A cohort of 583 consecutive patients undergoing urological cancer surgery was prospectively assessed using complete lower limb ultrasound at postoperative day 7 from January 2005 to July 2009. In all patients heparin and mechanical thromboprophylaxis were prescribed until complete ambulation. Potential variables predictive of venous thrombosis were analyzed. RESULTS: Complete data were available in 538 patients (463 male and 75 female), of whom 177 underwent nephrectomy, 86 radical cystectomy and 275 radical prostatectomy. A total of 40 deep venous thrombosis cases were found (7.4%), most of which were asymptomatic (92%) and limited to deep calf veins (80%). Of those asymptomatic deep venous thrombosis cases 86% were limited to deep calf veins. In all, 12 pulmonary embolisms were diagnosed, of which 4 were lethal. On multivariate analysis history of venous thromboembolism (OR 5.16, p = 0.02) and radical cystectomy (OR 3.47, p = 0.002) were independently associated with venous thromboembolism. CONCLUSIONS: Lower extremity venous thromboembolism has a high rate of occurrence after urological surgery for cancer despite the recommended venous thromboembolism prophylaxis. Most cases are asymptomatic and limited to deep calf veins. Our results suggest that complete lower limb ultrasound should be performed early after radical cystectomy and in patients with a personal history of venous thromboembolism.

Laparoscopic transposition of the left renal vein into the inferior vena cava for nutcracker syndrome.

Reimplantation of the left renal vein into the infrarenal inferior vena cava is the standard surgical procedure for nutcracker syndrome. A 40-year-old woman with a solitary left kidney suffered from left lumbar pain and hematuria. Imaging techniques found a large kidney with nutcracker syndrome. A totally laparoscopic transposition of the left renal vein was performed. Twelve months later, the patient is improved and has no more hematuria. Duplex scan showed no residual stenosis. Laparoscopic transposition of the left renal vein into the inferior vena cava is feasible with short length of stay and good short-term result.

Management of pregnancy in women with previous left ilio-caval stenting.

BACKGROUND: Ilio-caval stenting now represents the first line treatment for disabling obstructive ilio-caval lesions. Most patients are young women of child-bearing age. We herein report our experience of pregnancy in women who have a history of ilio-caval stenting. MATERIALS AND METHODS: From November 1995 to April 2008, 119 patients had ilio-caval stenting for obstructive venous disease in our department. Of these, 62 women were able to become pregnant. When pregnancy occurred, they received preventive treatment with low molecular weight heparin (LMWH) from the 3rd month of pregnancy to 1 month after delivery and had to wear elastic stockings. Patients also had to sleep on their right side if possible. They were followed during the pregnancy by duplex scanning at 3, 6, and 8 months, and then 1 month after delivery. RESULTS: Eight pregnancies occurred in 6 patients (mean age 26.5 years) who had a patent self-expanding stent (1 patient had 3 pregnancies). They had stenting for May-Thurner disease in 3 patients, for post-deep venous thrombosis (DVT) left common iliac vein occlusion in 1 patient, and during venous thrombectomy in 2 patients. All stents were self-expanding metallic stents located on the left common iliac vein. One patient had unrelated spontaneous abortion after 2 months of pregnancy. No DVT or symptomatic pulmonary embolism occurred during pregnancy, delivery, or during the postpartum period. Four patients needed cesarean delivery and none had hemorrhagic complications. None of the patients had adverse effects from the treatment. Duplex scan showed compression of the stent(s) at 8 months in 4 patients with inflow obstruction in 3 patients. Postpartum duplex-scan showed no remaining stenosis in all patients. No stents had structural damage. CONCLUSION: Ilio-caval stent compression can occur during pregnancy but does not lead to structural damage to the self-expanding stents. Despite this, no cases of DVT occurred with preventive LMWH treatment.

Laparoscopy-assisted left ovarian vein transposition to treat one case of posterior nutcracker syndrome.

We report one case of posterior nutcracker syndrome treated by left ovarian vein (LOV) transposition. A 36-year-old woman was suffering from nutcracker syndrome associated with pelvic congestion syndrome. Color duplex scan, computed tomographic scan, and angiography demonstrated a stenosis of a retroaortic left renal vein with proximal dilatation and incompetence of the LOV. The renocaval pullback gradient was 10 mm Hg. The LOV was harvested laparoscopically and transposed into the inferior vena cava. Completion angiography showed a patent reconstruction with no significant gradient. At day 4, an asymptomatic thrombosis was treated by thromboaspiration. Forty months later, the patient remained asymptomatic with a patent transposition. Posterior nutcracker syndrome is a rare condition. When associated with pelvic congestion syndrome due to LOV reflux, it can be treated by LOV transposition.

Tyrosine plays a dominant functional role in the paratope of a synthetic antibody derived from a four amino acid code.

The antigen-binding fragment Fab-YADS2 recognizes vascular endothelial growth factor (VEGF) and was derived from a library with chemical diversity restricted to only four amino acids (Tyr, Ser, Ala and Asp). The structure of the Fab:antigen complex revealed that the structural paratope is dominated by Tyr side-chains. Isothermal titration calorimetry and cell-based assays show that restricted chemical diversity does not limit the affinity or specificity of Fab-YADS2, which behaves in a manner comparable to natural antibodies. Mutagenesis experiments reveal that the functional paratope is dominated by Tyr, which represents 11 of the 15 functionally important residues. However, mutagenesis experiments also indicate that substitution of any of these tyrosine residues by Phe does not significantly affect binding to VEGF. Furthermore, saturation mutagenesis shows that replacement of three functionally important tyrosine residues by combinations of other hydrophobic residues is not only tolerated, but can actually improve affinity. The results support a model for naïve antigen recognition in which large Tyr side-chains establish binding contacts with antigen, and small Ser and Ala side-chains serve as auxiliaries that help to position Tyr in favorable binding conformations. While Tyr may not be optimal for any particular antigen contact, it is nonetheless capable of mediating favorable interactions with a diverse array of surfaces. Furthermore, the side-chain hydroxyl group makes Tyr significantly more hydrophilic than Phe and other hydrophobic amino acids. Increased hydrophilicity may reduce non-specific binding in the unbound state, and this may be critical for a naïve repertoire that is exposed to a diverse range of potential antigenic surfaces. The results show that the chemical nature of Tyr endows the amino acid with a privileged role in antigen recognition, and this likely explains the high abundance of Tyr in natural antigen-binding sites.

Training to yoga respiration selectively increases respiratory sensation in healthy man.

Because yoga practitioners think they are benefiting from their breath training we hypothesized that yoga respiration training (YRT) could modify the respiratory sensation. Yoga respiration (YR) ("ujjai") consisted of very slow, deep breaths (2-3 min(-1)) with sustained breath-hold after each inspiration and expiration. At inclusion in the study and after a 2-month YRT program, we determined in healthy subjects their eupneic ventilatory pattern and their capacity to discriminate external inspiratory resistive loads (respiratory sensation), digital tactile mechanical pressures (somesthetic sensation) and sound-pressure stimulations (auditory sensation). Data were compared to a gender-, age-, and weight-matched control group of healthy subjects who did not undergo the YRT program but were explored at the same epochs. After the 2-month YRT program, the respiratory sensation increased. Thus, both the exponent of the Steven's power law (Psi=kPhin) and the slope of the linear-linear plot between Psi and mouth pressure (Pm) were significantly higher, and the intercept with ordinate axis of the Psi versus Pm relationship was lower. After YRT, the peak Pm developed against inspiratory loads was significantly lower, reducing the load-induced activation of respiratory afferents. YRT induced long-lasting modifications of the ventilatory pattern with a significant lengthening of expiratory duration and a modest tidal volume increase. No significant changes in somesthetic and auditory sensations were noted. In the control group, the respiratory sensation was not modified during a 15-min period of yoga respiration, despite the peak Pm changes in response to added loads were then significantly reduced. These data suggest that training to yoga respiration selectively increases the respiratory sensation, perhaps through its persistent conditioning of the breathing pattern.

Design of synthetic autonomous VH domain libraries and structural analysis of a VH domain bound to vascular endothelial growth factor.

We compared the capacity of an autonomous heavy chain variable (VH) domain (VH-B1a) to support diversity within its antigen-binding site relative to the conventional antigen-binding fragment (Fab) from which it was derived. We find that VH-B1a can tolerate significant diversity within all three complementarity-determining regions (CDRs) and also within framework 3, and thus, VH-B1a and the Fab are similar in terms of the regions of the antigen-binding site that can tolerate diversity without compromising stability. We constructed libraries of synthetic VH domains and isolated binders with moderate affinity for vascular endothelial growth factor (VEGF) from a library in which only CDR3 was randomized. One binder was subjected to affinity maturation to derive an autonomous VH domain (VH-V1a) that recognized both human and mouse VEGF with high affinity (KD=16nM or 10nM, respectively). Structural analysis revealed that VH-V1a binds to an epitope that is distinct from the epitopes of a natural VEGF receptor and six different anti-VEGF Fabs. Moreover, VH-V1a recognizes VEGF by using an unusual paratope consisting predominantly of CDR3 but with significant contributions from framework residues within the former light chain interface. These results suggest that VH-B1a and other autonomous VH domains may be useful scaffolds to support both conventional libraries with antigen-binding sites built from the three CDR loops and, also, nonconventional libraries with antigen-binding sites built from CDR3 and the former light chain interface.

Role of quenching on superdiffusive transport in two-dimensional random media.

Transport in random media is known to be affected by quenched disorder. From the point of view of random walks, quenching induces correlations between steps that may alter the dynamical properties of the medium. This paper is intended to provide more insight into the role of quenched disorder on superdiffusive transport in two-dimensional random media. The systems under consideration are disordered materials called Lévy glasses that exhibit large spatial fluctuations in the density of scattering elements. We show that in an ideal Lévy glass the influence of quenching can be neglected, in the sense that transport follows to very good approximation that of a standard Lévy walk. We also show that, by changing sample parameters, quenching effects can be increased intentionally, thereby making it possible to investigate systematically diverse regimes of transport. In particular, we find that strong quenching induces local trapping effects which slow down superdiffusion and lead to a transient subdiffusivelike transport regime close to the truncation time of the system.

Late results of surgical venous thrombectomy with iliocaval stenting.

PURPOSE: Iliac vein occlusive disease leads to 73% of rethrombosis that occurs after venous thrombectomy when left untreated. The goal of this study is to present our long-term results of stenting of iliocaval occlusive lesions persisting after surgical venous thrombectomy. METHODS: From November 1995 to April 2007, 29 patients (19 women), with a median age of 38 years, had surgical venous thrombectomy with creation of an arteriovenous fistula and angioplasty and stenting. All were admitted for acute (<10 days) deep venous thrombosis (DVT) involving the iliocaval segment, of which eight had concomitant acute pulmonary embolism. Six patients had a history of DVT (2 with previous venous thrombectomy), two were pregnant, and three had postpartum DVT. No patients had short- or mid-term life-threatening factors. The underlying lesion was left iliocaval compression (May-Thurner syndrome) in 22 patients, chronic left common iliac vein occlusion in 3, residual clot in 3, and compression of the left external iliac vein by the left internal iliac artery in 1. RESULTS: Neither perioperative death nor pulmonary embolism occurred. Four early complications occurred after stenting (13.8%). Median hospital length of stay was 8 days (range, 5-22 days). Median follow-up was 63 months (range, 2-137 months). Three late complications occurred (10.3 %): one rethrombosis due to stent crushing during pregnancy and two restenosis, which were treated by iterative stenting. At the end of the follow-up, the median venous clinical severity score was 3 (range 1-12) and the venous disability score was 1 (range 0-2). Primary, assisted primary and secondary patency rates were, respectively, 79%, 86%, and 86% at 12, 60, and 120 months. Patients with patent iliocaval segments had significantly fewer infrainguinal obstructive lesions (4% vs 50%) and a higher rate of valvular competence (76% vs 0%) than those who experienced rethrombosis. Venous scores were also worse in patients with rethrombosis. CONCLUSION: Stenting is a safe, efficient, and durable technique to treat occlusive iliocaval disease after venous thrombectomy. Its use can prevent most of the rethrombosis that occurs after venous thrombectomy without major adverse effects.

Comprehensive analysis of the factors contributing to the stability and solubility of autonomous human VH domains.

We report a comprehensive analysis of sequence features that allow for the production of autonomous human heavy chain variable (V(H)) domains that are stable and soluble in the absence of a light chain partner. Using combinatorial phage-displayed libraries and conventional biophysical methods, we analyzed the entire former light chain interface and the third complementarity determining region (CDR3). Unlike the monomeric variable domains of camelid heavy chain antibodies (V(H)H domains), in which autonomous behavior depends on interactions between the hydrophobic former light chain interface and CDR3, we find that the stability of many in vitro evolved V(H) domains is essentially independent of the CDR3 sequence and instead derives from mutations that increase the hydrophilicity of the former light chain interface by replacing exposed hydrophobic residues with structurally compatible hydrophilic substitutions. The engineered domains can be expressed recombinantly at high yield, are predominantly monomeric at high concentrations, unfold reversibly, and are even more thermostable than typical camelid V(H)H domains. Many of the stabilizing mutations are rare in natural V(H) and V(H)H domains and thus could not be predicted by studying natural sequences and structures. The results demonstrate that autonomous V(H) domains with structural properties beyond the scope of natural frameworks can be derived by using non-natural mutations, which differ from those found in camelid V(H)H domains. These findings should enable the development of libraries of synthetic V(H) domains with CDR3 diversities unconstrained by structural demands.

Endovascular stenting in the treatment of pelvic vein congestion caused by nutcracker syndrome: lessons learned from the first five cases.

BACKGROUND: Compression of the left renal vein between the aorta and the superior mesenteric artery is a rare but possibly underestimated condition. Surgical correction (42 cases reported in the literature) can be performed by means of a variety of different techniques. Although endovascular stenting is well accepted for iliocaval occlusive disease, it has been poorly evaluated in this indication. We describe five patients who were treated for nutcracker syndrome by using stenting and analyze the nine cases previously reported. METHODS: From November 2002 to September 2004, five women (mean age, 34.7 years) were admitted for endovascular treatment of a nutcracker syndrome. They all had incapacitating pelvic congestion syndrome, including two with a history of left ovarian vein embolization; moreover, two had left lumbar pain, and three had hematuria. The mean preoperative venous disability score was 2.4. The patients underwent a gynecologic examination and laparoscopy to eliminate other causes of pelvic pain. The laparoscopy revealed large pelvic varicose veins and no signs of endometriosis. Duplex scan, computed tomographic scan, and iliocavography revealed left renal vein compression, with proximal distention and collateral pathways, with dilatation and permanent reflux in the left ovarian vein in the three patients who had not had prior embolization. The mean renocaval pullback gradient was 4.3 mm Hg. A percutaneous endovascular procedure, during in which a self-expanding metallic stent was implanted, was performed under general anaesthesia. RESULTS: Technical success was achieved in all cases. One case of stent migration occurred: the stent was pulled down in the inferior vena cava, with uneventful follow-up (mean, 14.3 months). One month later, patients were all improved and stents were patent at the duplex scan examination, without restenosis. The mean venous disability score was 1. No further left ovarian vein reflux was evident at duplex scan in patients who did not have prior embolization. Pelvic pain recurred in one patient who had initially improved, and endometriosis was diagnosed 15 months after the procedure. Two other patients, who received 40-mm-long stents, had a secondary recurrence of the symptoms caused by stent dislodgement. The two other patients were asymptomatic. CONCLUSIONS: This study shows that stenting is feasible, but some guidelines should be followed, mainly the use of long stents protruding into the inferior vena cava. Stenting can eliminate the symptoms of the condition, and the technique is only very slightly invasive. Further experience and follow-up are needed before accepting such a procedure for treatment of the nutcracker syndrome.

Mid-term results of endovascular treatment for symptomatic chronic nonmalignant iliocaval venous occlusive disease.

BACKGROUND: The goal of this article is to present clinical and patency results of endovascular treatment of nonmalignant, iliocaval venous obstructive disease and to discuss the evolution of technical details. METHODS: From November 1995 to June 2004, 44 patients (female-male ratio, 3.9:1; left-right lower limb ratio, 8.6:1; median age, 42 years; range, 21-80 years) had treatment for chronic disabling obstructive venous insufficiency with iliocaval stenosis or occlusion. The clinical class of CEAP was 2 in 11 limbs, 3 in 31, 4 in 4, 5 in 1, and 6 in 1; etiology was primary in 32 patients, secondary in 10, and congenital in 2. Anatomic involvement included superficial veins in 16 patients and perforator veins in 11. Obstruction was associated with superficial reflux in 4 patients, deep reflux in 13, and both in 13. Ten patients had occlusion. All procedures were performed in the operating room with perioperative angiography and angioplasty with or without self-expanding stent implantation. Venous clinical severity and disability scores were obtained before and after treatment. Patency and restenosis were evaluated by duplex Doppler ultrasonography. RESULTS: No perioperative death or pulmonary embolism occurred. The technical success rate was 95.5% (two recanalization failures), and two (4.5%) perioperative stent migrations occurred. One early thrombosis (2.4%) was treated by thrombectomy and creation of an arteriovenous fistula. One late death and one thrombosis occurred. Restenoses were found in five patients and were all treated successfully (four needed iterative stenting). Median follow-up was 27 months (range, 2-103 months). Median venous clinical severity score improved from 8.5 to 2, and median venous disability score improved from 2 to 0. Cumulative primary, assisted primary, and secondary patency rates of the venous segments at 36 months were 73%, 88%, and 90%, respectively, in intention to treat. The survival rate was 100% at 12 months and 97.3% at 60 months. CONCLUSIONS: Endovascular treatment of benign iliocaval occlusive disease is a safe and efficient minimally invasive technique with good mid-term patency rates. Moreover, it improves cases with obstruction only, as well as cases with associated reflux and obstruction. Primary stenting should always be performed by using self-expanding stents deployed under general anesthesia to avoid lumbar pain. In case of failure, the endovascular procedure does not preclude further surgical reconstruction.

Laparoscopy-assisted reconstruction to treat severe aortoiliac occlusive disease: early and midterm results.

OBJECTIVES: The purpose of this study was to evaluate the consequences on patient selection and on early and midterm results of the learning curve of a surgical team performing laparoscopy-assisted surgery in the treatment of severe aortoiliac occlusive disease (AIOD). PATIENTS AND METHOD: Between January 1998 and June 2003, 58 patients (53 men, 5 women; mean age, 59.5 years [range, 37-76 years]) were included in a prospective study and underwent a laparoscopy-assisted aortofemoral reconstruction with graft implantation through a 5-cm to 8-cm minilaparotomy. Fifty-one patients (88%) had claudication (category 2 or 3, Rutherford classification), and seven patients (12%) had tissue loss; at presentation they had TransAtlantic Inter-Society Consensus C (n=24, 41.4 %) or D (n=32, 55.2%) iliac lesions, and the last 2 patients (3.4%) had severe aortic lesions. Perioperative data for the first 29 patients, obtained during the first 34 months of the study (group 1), were compared with data for the last 29 patients, obtained during the last 32 months of the study (group 2). Follow-up consisted of clinical examination or duplex scanning, or both, at 1, 3, 6, and 12 months and yearly thereafter, and computed tomography before discharge and then every 2 years. RESULTS: One intraoperative surgical conversion (1.7%) was necessary, and two other patients (3.4%) died in the immediate postoperative period. With experience, initial contraindications such as obesity or suprarenal artery aortic clamping were eliminated, making it possible to increase the percentage of patients included, from 53.7% during the first 34 months to 90.6% during the last 32 months (P=.003). The mean duration of the operative procedure decreased from 285 minutes in group 1 to 192 minutes in group 2 (P<.001), and the mean duration of aortic clamping decreased from 76.4 minutes in group 1 to 31.8 minutes in group 2 (P<.001). The number of early repeat interventions was reduced from three (10.3%) in group 1 to 2 (6.9%) in group 2 (P=NS), and the clinical recovery period decreased from 7 days to 4.5 days (P=.05). During a mean follow-up of 26.7 months (range, 1-66 months) there were 5 repeat surgeries (9%) to treat late graft occlusion, establishing midterm primary and secondary patency rates of 89.3% and 91%, respectively. No aortic false aneurysms were detected, and no major amputations were performed. CONCLUSION: These preliminary results assess the feasability and the safety of this minimally invasive video-assisted technique. A short period of postoperative recovery and good midterm patency rate are the two main benefits of this new surgical option.

Laparoscopy-assisted abdominal aortic aneurysm endoaneurysmorraphy: early and mid-term results.

OBJECTIVES: This study was undertaken to evaluate the consequences on patient selection and on early and mid-term results during the learning curve of a surgical team performing laparoscopy-assisted surgery to treat abdominal aortic aneurysm (AAA). PATIENTS AND METHODS: Between December 1998 and January 2002, 24 patients (22 men, 2 women; mean age, 68.2 years [range, 57-82 years]) were included in a prospective study and underwent laparoscopic transperitoneal AAA dissection followed by graft implantation through a 6 to 9 cm minilaparotomy. Perioperative data for the first 10 patients, obtained during the first 25 months of the study (group 1), were compared with data for the last 14 patients, obtained during the last 13 months of the study (group 2). Follow-up consisted of clinical examination or duplex scanning, or both, at 1, 3, 6, and 12 months and yearly thereafter, and computed tomographic scanning before discharge and yearly thereafter. RESULTS: One patient (4.3%) died in the immediate postoperative period. In this patient and two others (12.5%), the minilaparotomy was extended intraoperatively, from 12 cm to 16 cm. With experience, initial contraindications such as obesity and short proximal or calcified aortic neck were eliminated, enabling increase in rate of patients included, from 27.7% during the first 25 first months to 56% during the last 13 months (P =.063). Mean duration of operative clamping decreased from 275 minutes in group 1 to 195 minutes in group 2 (P <.0001), and mean duration of aortic clamping decreased from 101 minutes in group 1 to 52 minutes in group 2 (P <.0001). The number of early repeat interventions was reduced from 3 (30%) in group 1 to 2 (14.3%) in group 2 (P =.61), and clinical recovery period decreased from 6.8 days to 4.3 days (P <.005). During mean follow-up of 17.1 months (range, 3-38 months), no late aortoiliac procedures were necessary and no prosthetic abnormality was detected. CONCLUSION: This minimally invasive video-assisted technique provides good postoperative comfort and excellent mid-term results. Developments in experience and instrumentation have enabled us to include a growing number of patients and to reduce the duration of the procedure.