New Direct Limit on Neutrinoless Double Beta Decay Half-Life of

The Cryogenic Underground Observatory for Rare Events (CUORE) at Laboratori Nazionali del Gran Sasso of INFN in Italy is an experiment searching for neutrinoless double beta (0νßß) decay. Its main goal is to investigate this decay in ^{130}Te, but its ton-scale mass and low background make CUORE sensitive to other rare processes as well. In this Letter, we present our first results on the search for 0νßß decay of ^{128}Te, the Te isotope with the second highest natural isotopic abundance. We find no evidence for this decay, and using a Bayesian analysis we set a lower limit on the ^{128}Te 0νßß decay half-life of T_{1/2}>3.6×10^{24} yr (90% CI). This represents the most stringent limit on the half-life of this isotope, improving by over a factor of 30 the previous direct search results, and exceeding those from geochemical experiments for the first time.

Buckling versus unilateral constraint for a multistable metamaterial element.

A structural element is designed and investigated, forming the basis for the development of an elastic multistable metamaterial. The leitmotif of the structural design is the implementation of a strut characterized by a bifurcation occurring at either vanishing tensile or compressive load. It is shown that buckling at null load leads to a mechanical equivalence with a unilateral constraint formulation, introducing shocks in dynamics. Towards a future analysis of the latter, the nonlinear quasi-static response is investigated, showing the multistable character of the structure, which may appear as bistable or tetrastable. This article is part of the theme issue 'Wave generation and transmission in multi-scale complex media and structured metamaterials (part 1)'.

Oligo metastatic renal cell carcinoma: stereotactic body radiation therapy, if, when and how?

BACKGROUND AND PURPOSE: Renal cell carcinoma (RCC) has traditionally been considered radioresistant with a limited role for conventional fractionation as a local approach. Nevertheless, since the appearance of stereotactic body radiation therapy (SBRT), radiotherapy (RT) has been increasingly employed in the management of metastatic RCC (mRCC). The aim of this study was to evaluate the role of SBRT for synchronous and metachronous oligo metastatic RCC patients in terms of local control, delay of systemic treatment, overall survival and toxicity. PATIENTS AND METHODS: A Monocentric single institution retrospective data collection was performed. Inclusion criteria were: (1) oligo-recurrent or oligo-progressive disease (less than 5 metastases) in mRCC patients after radical/partial nephrectomy or during systemic therapy, (2) metastasectomy or other metastasis-directed, rather than SBRT not feasible, (3) any contraindication to receive systemic therapy (such as comorbidities), (4) all the histologies were included, (5) available signed informed consent form for treatment. Tumor response and toxicity were evaluated using the response evaluation criteria in solid tumors and the Common Terminology Criteria for Adverse Events version 4.03, respectively. Progression-free survival in-field and out-field (in-field and out-field PFS) and overall survival (OS) were calculated via the Kaplan-Meier method. The drug treatment-free interval was calculated from the start of SBRT to the beginning of any systemic therapy. RESULTS: From 2010 to December 2018, 61 patients with extracranial and intracranial metastatic RCC underwent SBRT on 83 lesions. Intracranial and extracranial lesions were included. Forty-five (74%) patients were treated for a solitary metastatic lesion. Median RT dose was 25 Gy (range 10-52) in 5-10 fractions. With a median follow-up of 2.3 years (range 0-7.15), 1-year in-field PFS was 70%, 2-year in-field PFS was 55%. One year out-field PFS was 39% and 1-year OS was 78%. Concomitant systemic therapy was employed for only 11 (18%) patients, for the others 50 (82%) the drug treatment-free rate was 70% and 50% at 1 and 2 years, respectively. No > G1 acute and late toxicities were reported. CONCLUSION: The pattern of failure was pre-dominantly out-of-field, even if the population was negatively selected and the used RT dose could be considered palliative. Therefore, SBRT appears to be a well-tolerated, feasible and safe approach in oligo metastatic RCC patients with an excellent in-field PFS. SBRT might play a role in the management of selected RCC patients allowing for a delay systemic therapy begin (one out of two patients were free from new systemic therapy at 2 years after SBRT). Further research on SBRT dose escalation is warranted.

Comparison of the performance of a high voltage generator insulated by gas or liquid dielectric.

A module of a wireless high voltage generator was tested immersed in both gaseous and liquid environments providing electrical insulation. The overall performance of the module as well as a detailed performance of the key components are reported, and a comparison between the results in gas and liquid is given. The tests performed on the liquid dielectric show that it is a valid alternative to high pressure gas electrical insulation.

The association between pesticide use and cutaneous melanoma: a systematic review and meta-analysis.

BACKGROUND: The incidence of cutaneous melanoma (CM), the deadliest form of skin cancer, has gradually increased in the last decades among populations of European origin. Epidemiological studies suggested that farmers and agricultural workers are at an increased risk of CM because they were exposed to pesticides. However, little is known about the relationship between pesticides and CM. OBJECTIVES: To investigate the association between exposure to pesticides and CM by systematically reviewing the literature. Secondary aim was to determine the categories of pesticides mainly involved in CM development. METHODS: A systematic review of the literature was performed up to September 2018 using MEDLINE, Embase and Web of Science. Studies assessing CM risk in licensed pesticide applicators were considered. Strict criteria were established to select independent studies and risk estimates; random effect models, taking into account heterogeneity, were applied. A pooled risk estimate for CM was calculated for the use of each type of pesticide and type of exposure. Between-study and estimate heterogeneity was assessed and publication bias investigated. RESULTS: A total of nine studies (two case-controls and seven cohorts) comprising 184 389 unique subjects were included. The summary relative risks for the categories 'herbicides - ever exposure', 'insecticides - ever exposure', 'any pesticide - ever exposure' and 'any pesticide - high exposure' resulted 1.85 [95% confidence interval (CI): 1.01, 3.36], 1.57 (95% CI: 0.58, 4.25), 1.31 (95% CI: 0.85, 2.04) and 2.17 (95% CI: 0.45, 10.36), respectively. Herbicides and insecticides had no between-study heterogeneity (I2  = 0%), while a significant heterogeneity (I2  > 50%) was detected for the high exposure to any pesticide. No indication for publication bias was found. CONCLUSIONS: Individuals exposed to herbicides are at an increased risk of CM. Future properly designed observational studies are required to confirm this finding.

Nested Bloch waves in elastic structures with configurational forces.

Small axial and flexural oscillations are analysed for a periodic and infinite structure, constrained by sliding sleeves and composed of elastic beams. A nested Bloch-Floquet technique is introduced to treat the nonlinear coupling between longitudinal and transverse displacements induced by the configurational forces generated at the sliding sleeve ends. The action of configurational forces is shown to play an important role from two perspectives. First, the band gap structure for purely longitudinal vibration is broken so that axial propagation may occur at frequencies that are forbidden in the absence of a transverse oscillation and, second, a flexural oscillation may induce axial resonance, a situation in which the longitudinal vibrations tend to become unbounded. The presented results disclose the possibility of exploiting configurational forces in the design of mechanical devices towards longitudinal actuation from flexural vibrations of small amplitude at given frequency. This article is part of the theme issue 'Modelling of dynamic phenomena and localization in structured media (part 1)'.

Serpentine locomotion through elastic energy release.

A model for serpentine locomotion is derived from a novel perspective based on concepts from configurational mechanics. The motion is realized through the release of the elastic energy of a deformable rod, sliding inside a frictionless channel, which represents a snake moving against lateral restraints. A new formulation is presented, correcting previous results and including situations never analysed so far, as in the cases when the serpent's body lies only partially inside the restraining channel or when the body has a muscle relaxation localized in a small zone. Micromechanical considerations show that propulsion is the result of reactions tangential to the frictionless constraint and acting on the snake's body, a counter-intuitive feature in mechanics. It is also experimentally demonstrated that the propulsive force driving serpentine motion can be directly measured on a designed apparatus in which flexible bars sweep a frictionless channel. Experiments fully confirm the theoretical modelling, so that the presented results open the way to exploration of effects, such as variability in the bending stiffness or channel geometry or friction, on the propulsive force of snake models made up of elastic rods.

From the elastica compass to the elastica catapult: an essay on the mechanics of soft robot arm.

An elastic rod is clamped at one end and has a dead load attached to the other (free) end. The rod is then slowly rotated using the clamp. When the load is smaller than the buckling value, the rod describes a continuous set of quasi-static forms and its end traces a (smooth, convex and simple) closed curve, which would be a circle if the rod were rigid. The closed curve is analytically determined through the integration of the Euler's elastica, so that for sufficiently small loads the mechanical system behaves as an 'elastica compass'. For loads higher than that of buckling, the elastica reaches a configuration from which a snap-back instability occurs, realizing a sort of 'elastica catapult'. The whole quasi-static evolution leading to the critical configuration for snapping is calculated through the elastica and the subsequent dynamic motion simulated using two numerical procedures, one ad hoc developed and another based on a finite-element scheme. The theoretical results are then validated on a specially designed and built apparatus. An obvious application of the present model would be in the development of soft robotic limbs, but the results are also of interest for the optimization analysis in pole vaulting.

Publisher's Note: Asymptotic self-restabilization of a continuous elastic structure [Phys. Rev. E 94, 063005 (2016)].

This corrects the article DOI: 10.1103/PhysRevE.94.063005.

Microdosimetric Measurements in Gamma and neutron Fields with a Tissue Equivalent Proportional Counter Based on a Gas Electron Multiplier.

A multi-element tissue-equivalent proportional counter (TEPC), based on a single gas electron multiplier (GEM) foil of standard geometry, has been constructed with 16 cylindrical sensitives volumes. In this article, the design of this novel counter is described and first microdosimetric measurements are presented. To study the response of the GEM-TEPC to both low and high linear energy transfer radiation fields, the microdosimetric spectra due to a 137Cs gamma-ray source and to fast neutrons from 7Li(d,n)8Be reaction have been measured using pure propane gas at low pressure, in order to simulate a tissue site of about 1 µm equivalent size. The comparison with spectra measured with a spherical TEPC and with a mini-TEPC demonstrates promising properties for application of the GEM-TEPC for microdosimetric applications.

Asymptotic self-restabilization of a continuous elastic structure.

A challenge in soft robotics and soft actuation is the determination of an elastic system that spontaneously recovers its trivial path during postcritical deformation after a bifurcation. The interest in this behavior is that a displacement component spontaneously cycles around a null value, thus producing a cyclic soft mechanism. An example of such a system is theoretically proven through the solution of the elastica and a stability analysis based on dynamic perturbations. It is shown that the asymptotic self-restabilization is driven by the development of a configurational force, of similar nature to the Peach-Koehler interaction between dislocations in crystals, which is derived from the principle of least action. A proof-of-concept prototype of the discovered elastic system is designed, realized, and tested, showing that this innovative behavior can be obtained in a real mechanical apparatus.

Self-encapsulation, or the 'dripping' of an elastic rod.

A rod covering a fixed span is loaded at the middle with a transverse force, such that with increasing load a progressive deflection occurs. After a certain initial deflection, a phenomenon is observed where two points of the rod come in contact with each other. This is defined as the 'dripping point' and is when 'self-encapsulation' of the elastic rod occurs. Dripping seems at a first glance to be impossible and definitely cannot occur in the presence of 'ordinary' constraints (such as simple supports or clamps) at the ends of the span. However, the elastica governs oscillating pendulums, buckling rods and pendant drops, so that a possibility for self-encapsulation might be imagined. This phenomenon is indeed demonstrated (both theoretically and experimentally) to occur when at least one of the constraints at the ends of the rod is a sliding sleeve. This mechanical device generates a configurational force, causing the dripping of the rod, in a fully elastic set-up.

Torsional locomotion.

One edge of an elastic rod is inserted into a friction-less and fitting socket head, whereas the other edge is subjected to a torque, generating a uniform twisting moment. It is theoretically shown and experimentally proved that, although perfectly smooth, the constraint realizes an expulsive axial force on the elastic rod, which amount is independent of the shape of the socket head. The axial force explains why screwdrivers at high torque have the tendency to disengage from screw heads and demonstrates torsional locomotion along a perfectly smooth channel. This new type of locomotion finds direct evidence in the realization of a 'torsional gun', capable of transforming torque into propulsive force.

An elastica arm scale.

The concept of a 'deformable arm scale' (completely different from a traditional rigid arm balance) is theoretically introduced and experimentally validated. The idea is not intuitive, but is the result of nonlinear equilibrium kinematics of rods inducing configurational forces, so that deflection of the arms becomes necessary for equilibrium, which would be impossible for a rigid system. In particular, the rigid arms of usual scales are replaced by a flexible elastic lamina, free to slide in a frictionless and inclined sliding sleeve, which can reach a unique equilibrium configuration when two vertical dead loads are applied. Prototypes designed to demonstrate the feasibility of the system show a high accuracy in the measurement of load within a certain range of use. Finally, we show that the presented results are strongly related to snaking of confined beams, with implications for locomotion of serpents, plumbing and smart oil drilling.

Sacral neuromodulation for neurogenic non-obstructive urinary retention in incomplete spinal cord patients: a ten-year follow-up single-centre experience.

OBJECTIVE: To determine the success rate of percutaneous first stage of sacral neuromodulation (SNM) and the efficacy and safety of permanent SNM for incomplete spinal cord lesion (SCL) patients suffering from chronic neurogenic non-obstructive urinary retention (N-NOR). METHOD: From January 2003 to December 2012, 85 individuals underwent the percutaneous first stage of SNM. Subsequently, only responders who reached a concomitant reduction by at least 50% of volume per catheterization and in the number of catheterizations per day comparing their 7-day voiding diaries at baseline underwent permanent SNM. Final follow-up was conducted by April 2013. RESULTS: Thirty-six individuals responded to percutaneous first stage of SNM. Post-surgery urodynamics documented all patients experiencing first sensation of bladder filling. A statistically significant increase in Qmax ml per sec and decrease in post-voiding residual urine per ml were documented. (P<0.01). First sensation of bladder filling at baseline represented a statistically significant parameter for the success of the first stage SNM (P<0.05). Eleven out of 34 patients at follow-ups were 'inconstant responders' because they returned to similar baseline voiding symptoms, but responded again with an implant on the controlateral S3 sacral root. Two failed twice and responded once again after an S4 sacral root implant. All but one failure occurred more than 3 years after the previous implant. Other drawbacks were resolved telemetrically. CONCLUSIONS: Research is needed to increase the success rate of the first stage SNM on incomplete SCL patients with N-NOR. Permanent SNM is highly efficacious in the medium follow-up.

A retrospective study on female urological surgeries over the 10 years following spinal cord lesion.

OBJECTIVES: To evaluate the efficacy and safety over a 10-year period of any urological operations required by female patients with spinal cord lesions (SCLs). METHODS: Retrospective study of urological surgeries from our database performed on females with SCLs from 2001 to 2002. Surgery efficacy for neurogenic lower urinary tract dysfunctions (N-LUTDs) was evaluated by comparing 7-day voiding diaries pre- and post-surgeries, while individual investigations were done pre- and post-surgery to evaluate urological complications. Drawbacks were assessed. RESULTS: Thirty-eight out of 69 patients underwent one or more urological procedures. Twenty-one out of 42 patients with suprasacral lesions underwent interventions for N-LUTD. The main surgical treatment was endoscopic detrusor infiltration of botulinum-A (Botox 300 UI or Dysport 750 UI) performed 107 times on 15 subjects using aseptic intermittent catheterizations for neurogenic overactive bladder. Mean efficacy duration was 9.2 months. Six females with infrasacral lesions underwent at least one intervention for N-LUTD. Two females in each group underwent tension-free vaginal tape for stress urinary incontinence (SUI), reducing episodes per week of SUI by >90% after 5 years. The most serious urological complication was active vesico-ureteral reflux (VUR) in three patients, treated endoscopically with submucosal injection of Macroplastique. No VUR recurrence was detected during a 6-year follow-up. All bladder stones (five cases) and renal calculi (five cases) were treated with endoscopic transurethrally electrohydraulic lithotripsy and extracorporeal shock-wave lithotripsy, respectively. Overall, no serious drawbacks were observed. CONCLUSIONS: Mini-invasive surgeries were exclusively used to address urological issues in chronic SCL patients.

Intravesical electrostimulation versus sacral neuromodulation for incomplete spinal cord patients suffering from neurogenic non-obstructive urinary retention.

OBJECTIVES: To compare the efficacy of intravesical electrostimulation (IVES) versus sacral neuromodulation (SNM) in patients with incomplete spinal cord lesions (SCL) and neurogenic non-obstructive urinary retention (N-NOR). METHODS: In this retrospective study, 77 N-NOR patients underwent IVES (minimum 28 sessions), then after returning to voiding baseline symptoms, percutaneous first stage of SNM (lasting for minimum 4 weeks). After the two neuromodulation treatments, responders were categorized as patients experiencing both a 50% reduction of volume per catheterization per ml and a 50% reduction in number of catheterizations per day when comparing the 7-day voiding diaries at the end of both procedures to baselines. New urodynamics were performed subsequently. Responders to first stage of SNM underwent permanent SNM. RESULTS: Forty-eight patients responded to neither of the treatments, whereas 29 responded to both IVES and first-stage SNM. No significant statistical differences (P>0.05) were detected in the voiding diaries. Following the two procedures, the first sensation of bladder filling was either maintained or recovered by all responders, whereas the same 11 patients reached a bladder contractility index of >100. The 29 IVES responders lost their clinical benefits in a mean follow-up of 9.6 months. Only 10 out of the 29 patients became nonresponsive to permanent SNM, in a mean follow-up of 54 months. CONCLUSION: A strict correlation in terms of clinical and urodynamic patterns was demonstrated in patients with incomplete SCL and N-NOR, following IVES and first stage of SNM. However, voiding improvement through IVES was short-term when compared with the effects of permanent SNM.

Preoperative paclitaxel and radiotherapy for locally advanced breast cancer: surgical aspects.

INTRODUCTION: Approximately 15% of breast cancer patients present with large tumors that involve the skin, the chest wall, or the regional lymph nodes. Multimodality therapy is required, to provide the best chance for long-term survival. We have developed a regimen of paclitaxel, with concomitant radiation, as a primary therapy in patients with locally advanced breast cancer. METHODS: Eligible patients had locally advanced breast cancer (stage IIB or III). After obtaining informed consent, patients received paclitaxel (30 mg/m2 during 1 hour) twice per week for 8 weeks and radiotherapy to 45 Gy (25 fractions, at 180 cGy/fraction, to the breast and regional nodes). Patients then underwent modified radical mastectomy followed by postoperative polychemotherapy. RESULTS: Twenty-nine patients were enrolled. Of these, 28 were assessable for clinical response and toxicity, and 27 were assessable for pathological response. Objective clinical response was achieved in 89%. At the time of surgery, 33% had no or minimal microscopic residual disease. Chemoradiation-related acute toxicity was limited; however, surgical complications occurred in 41% of patients. CONCLUSIONS: Preoperative paclitaxel with radiotherapy is well tolerated and provides significant pathological response, in up to 33% of patients with locally advanced breast cancer, but with a significant postoperative morbidity rate.

Spinal osteomyelitis after TPN catheter-induced septicemia.

Osteomyelitis of the spine is a well-recognized delayed manifestation of septicemia but has not been recognized as a complication of total parenteral nutrition. We report five cases of spinal osteomyelitis that were clinically recognized 1 to 13 months after total parenteral nutrition catheter-induced septicemia. Radiographic evidence of osteomyelitis was seen in all five patients. In three patients, culture of bony aspirates was positive for the same organism as from the blood. In one case, the diagnosis was established by histology, and in one the diagnosis was based on radiographic and radionuclide evidence of osteomyelitis. The organism responsible was Staphylococcus aureus in two cases, Candida albicans in another two cases and C tropicalis in one case. The septic episode that preceded osteomyelitis was treated with systemic antibiotics and catheter removal in four patients, and antibiotics without catheter removal in one patient. Nevertheless, osteomyelitis occurred, requiring bracing or operative debridement as well as prolonged antibiotic therapy. Spinal osteomyelitis may occur as a delayed manifestation of total parenteral nutrition catheter-induced septicemia. Prompt and effective treatment of septicemia is indicated but may not always be sufficient. Clinical suspicion is the key to the correct and early diagnosis of osteomyelitis and therefore to adequate treatment.