Ab Initio Uncertainty Quantification of Neutrinoless Double-Beta Decay in

The observation of neutrinoless double-beta (0νßß) decay would offer proof of lepton number violation, demonstrating that neutrinos are Majorana particles, while also helping us understand why there is more matter than antimatter in the Universe. If the decay is driven by the exchange of the three known light neutrinos, a discovery would, in addition, link the observed decay rate to the neutrino mass scale through a theoretical quantity known as the nuclear matrix element (NME). Accurate values of the NMEs for all nuclei considered for use in 0νßß experiments are therefore crucial for designing and interpreting those experiments. Here, we report the first comprehensive ab initio uncertainty quantification of the 0νßß-decay NME, in the key nucleus ^{76}Ge. Our method employs nuclear strong and weak interactions derived within chiral effective field theory and recently developed many-body emulators. Our result, with a conservative treatment of uncertainty, is an NME of 2.60_{-1.36}^{+1.28}, which, together with the best-existing half-life sensitivity and phase-space factor, sets an upper limit for effective neutrino mass of 187_{-62}^{+205} meV. The result is important for designing next-generation germanium detectors aiming to cover the entire inverted hierarchy region of neutrino masses.

The influence of motor function on processing speed in preterm and term-born children.

This study investigates the relationship between motor function and processing speed in preterm children. Processing speed was compared in 145 adolescents, born 25-41 weeks gestational age, utilizing tasks including differing motor demands. The influence of motor cortex excitability and functional motor skills on task performance was assessed. For tasks with motoric demands, differences in performance between preterm and term-born children were mediated by the relationship between gestational age, corticomotor excitability, and motor function. There were no differences in non-motor processing speed task performance between preterm and term-born children. Measures of processing speed may be confounded by a timed motor component.

Primary Intraosseous Malignant Peripheral Nerve Sheath Tumor of the Medial Cuneiform: A Case Report and Review of the Literature.

Peripheral nerve sheath tumors (benign and malignant) usually arise in the soft tissues and are unusual in bone. Intraosseous peripheral nerve sheath tumors are usually benign and constitute approximately 0.2% of all bone tumors. Intraosseous malignant peripheral nerve sheath tumors (MPNSTs) are uncommon and usually result from secondary invasion. Only a few cases of primary intraosseous MPNSTs have been reported in published studies, and these were localized mostly in the mandible (approximately 50%) or maxilla, spine, and, occasionally, in the appendicular skeleton. To the best of our knowledge, we report the first case of primary intraosseous MPNST involving a midtarsal bone (medial cuneiform). The patient was a 62-year-old female who presented with pain and tenderness but without swelling. Imaging revealed nonspecific findings, and the preoperative computed tomography-guided biopsy findings were consistent with MPNST. The patient was treated with neoadjuvant radiotherapy, followed by wide local excision and allograft reconstruction. At the final follow-up examination (24 months), the graft had been incorporated without evidence of local recurrence or distant disease. The patient with primary intraosseous MPNST of the medial cuneiform described in the present report presented with nonspecific clinical and radiologic findings. Thus, a high index of suspicion and histopathologic examination, including immunohistochemistry, are necessary for an accurate diagnosis.

The influence of short-interval intracortical facilitation when assessing developmental changes in short-interval intracortical inhibition.

OBJECTIVE: Measures of short-interval intracortical inhibition (SICI) can be contaminated by excitatory influences of short-interval intracortical facilitation (SICF), unless examined at individually-optimized interstimulus intervals (ISIs). We hypothesized that age-related differences in SICF would explain previously reported reduced SICI in children and adolescents compared with adults. METHODS: Fifty-one participants, aged 8-29years, underwent transcranial magnetic stimulation. SICF curves were constructed to determine the ISI at which SICF was minimal (i.e. the first trough). SICI curves were constructed at this individually-determined ISI with conditioning stimulus (S1) intensities of 60-110% of active motor threshold. RESULTS: There was no effect of age on the ISI corresponding with the SICF trough. However, there was a main effect of age on the amplitude of the conditioned motor-evoked potential at the different ISIs, such that children aged 8-12years demonstrated greater SICF than those aged 16-18 and 19-21years. There was no effect of age on SICI, and no interaction between age group and S1 intensity. CONCLUSIONS: Compared with that in older adolescents and young adults, SICF is enhanced in children aged 8-12years. Surprisingly, this enhanced SICF does not appear to reduce the degree of SICI that can be evoked at the first trough in this age group. SIGNIFICANCE: This is the first report of enhanced SICF in young children. It remains possible that enhanced SICF may have confounded earlier reports of reduced SICI in children less than 8years.

Inter- and intra-subject variability of motor cortex plasticity following continuous theta-burst stimulation.

BACKGROUND: The potential of non-invasive brain stimulation (NIBS) for studying, and inducing, functionally relevant neuroplasticity is dependent on protocols that can induce lasting, robust and reliable effects. A current limiting factor is the large inter- and intra-subject variability in NIBS-induced neuroplastic responses. There has been some study of inter-subject response variability and factors that contribute to it; however, intra-subject response variability has, so far, received little investigation. OBJECTIVES: By testing participants on multiple occasions we aimed to (1) compare inter- and intra-subject variability of neuroplastic responses induced by continuous theta-burst stimulation (cTBS); (2) determine whether the transcranial magnetic stimulation (TMS) intensity used to measure cTBS-induced neuroplastic responses contributes to response variability; (3) determine whether assessment of factors known to influence response variability can be used to explain some of the variability in cTBS-induced neuroplastic responses across experimental sessions. METHODS: In three separate experimental sessions, motor-evoked potential (MEP) input-output (IO) curves were obtained before and after cTBS, and questionnaire-based assessments of physical activity and perceived stress were obtained. RESULTS: cTBS-induced MEP suppression was greatest at the upper end of the IO curve (150-180% resting motor threshold; RMT) and most consistent across subjects and across experimental sessions when assessed with a TMS intensity of 150% RMT. The magnitude of cTBS-induced MEP suppression evoked at 150% RMT correlated with self-reported perceived stress, but not with self-reported physical activity. CONCLUSIONS: The most reliable TMS intensity to probe cTBS-induced long-term depression (LTD)-like neuroplastic responses is 150% RMT. This is unlikely to simply be a ceiling effect and, we suggest, may be due to changes in the descending volley evoked at higher stimulus intensities. The perceived stress scale appears to be sufficiently sensitive to measure the influence of subject stress on LTD-like neuroplastic responses.

Growth in early life and the development of obesity by age 9 years: are there critical periods and a role for an early life stressor?

OBJECTIVE: Rapid growth, possibly occurring in critical periods in early life, may be important for the development of obesity. It is unknown whether this is influenced by postnatal exposures such as age-relevant sources of stress. Frequent house moves may be one such stressor. We aimed to examine if there is a period of growth in early life critical for the development of child obesity by age 9 years and assess the role of house moves in modifying any relationships between early life growth and obesity at age 9 years. DESIGN: Prospective Australian birth cohort study. SUBJECTS: In all, 392 children with serial body size measurements from birth to age 9 years. METHODS: Standardized body mass index (z-BMI) was available for six time points (spanning birth to 3½ years), and the total number of house moves between birth and 3½ years. The outcomes considered were z-BMI and % body fat (%BF) at age 9 years. Linear regression models were used to estimate the effects of serial measurements of z-BMI and number of house moves on the outcomes. RESULTS: Life-course plots showed that z-BMI at 3½ years was a statistically significant predictor of z-BMI at 9 years (ß=0.80; standard error (s.e.), 0.04), whereas z-BMI at 9 months (ß=-1.13; s.e., 0.40) and 3½ years (ß=4.82; s.e., 0.42) were significant predictors of %BF at age 9 years. There were statistically significant interactions between the number of house moves and change in z-BMI between 9 and 12 months, such that ≥ 3 house moves in early life amplified the detrimental effects of earlier rapid growth on both body size and composition at age 9 years. CONCLUSION: In the absence of evidence for a single critical period, efforts to prevent overweight and obesity are required throughout childhood. In addition, modifiable postnatal stressors may exacerbate effects of early growth on obesity in later childhood.

Rupture of the ilio-psoas tendon after a total hip arthroplasty: an unusual cause of radio-lucency of the lesser trochanter simulating a malignancy.

Avulsion fracture or progressive radiolucency of lesser trochanter is considered a pathognomic finding in patients with malignancies. Although surgical release of the iliopsoas tendon may be required during a total hip arthroplasty (THA), there is no literature on spontaneous rupture of the ilio-psoas tendon after a THA causing significant functional impairment. We report here such a case, which developed progressive radiolucency of the lesser trochanter over six years after a THA, simulating a malignancy. The diagnosis was confirmed by MRI. Because of the chronic nature of the lesion, gross retraction of the tendon into the pelvis, and low demand of our patient, he was treated by physiotherapy and gait training. Injury to the ilio-psoas tendon can occur in various steps of the THA and extreme care should be taken to avoid this injury. Prevention during surgery is better, although there are no reports of repair in the THA setting. This condition should be considered in patients who present with progressive radioluceny of the lesser trochanter, especially in the setting of a hip/pelvic surgery. Awareness and earlier recognition of the signs and symptoms of this condition will aid in diagnosis and will direct appropriate management.

Squamous cell carcinoma of the foot.

BACKGROUND: Squamous cell carcinomas (SCC) of the foot are relatively common, but have been infrequently reported in the orthopaedic literature. MATERIALS AND METHODS: Twelve patients with SCC of the foot treated at a single institution from 1998 to 2005 were studied retrospectively with regard to risk factors for the disease, treatment, and functional and oncologic outcomes. The mean duration of postoperative followup was 43 (range, 24 to 105) months. RESULTS: Eight of the 12 patients had identifiable risk factors for SCC. Inadequate or inappropriate procedures had been previously performed in eight of the 12 cases, requiring more aggressive definitive treatment in at least four cases. Definitive operative treatment consisted of wide excision (4 patients), partial or complete toe amputation (4), partial foot amputation (3), and transtibial amputation (1). Two patients developed local recurrence of disease, and both ultimately required Syme amputations for local control. One patient with local recurrence died of metastatic disease and the other 11 patients are alive without evident disease. Musculoskeletal Tumor Society functional scores averaged 90 and were good or excellent in nine of the 11 surviving patients. CONCLUSION: Squamous cell carcinomas of the foot are likely underreported and frequently subject to inappropriate initial treatment. Most patients have identifiable risk factors for SCC that can aid in formulating an appropriate differential diagnosis. Despite frequent suboptimal initial treatment, most patients are candidates for complete or partial limb salvage, with generally good oncologic and functional outcomes expected.

Fungating soft-tissue sarcomas. Treatment implications and prognostic importance of malignant ulceration.

BACKGROUND: Several variables have been reported as being prognostic with regard to the outcomes of soft-tissue sarcomas. Although the tumors are subjectively ominous, no prior study has been performed to evaluate the treatment or prognosis of fungating soft-tissue sarcomas. METHODS: We performed a retrospective review of all soft-tissue sarcomas treated at our institution between 1989 and 2004 that had been followed for a minimum of two years or until the death of the patient. Our study group consisted of twenty-four patients with a primary high-grade fungating tumor, and our control group consisted of 146 consecutive patients with a primary high-grade non-fungating tumor. The study cohorts were compared with regard to disease presentation, treatment, and oncologic outcomes. RESULTS: There were no significant differences in tumor size, tumor depth, or histopathologic diagnoses between the cohorts, although the patients with a fungating tumor tended to be older (mean, sixty-five years compared with fifty-five years in the control group; p = 0.004) and have shorter postoperative follow-up (mean, thirty-eight months compared with sixty-five months in the control group; p = 0.03). The proportion of patients presenting with metastases was significantly greater in the group with a fungating tumor (33% compared with 9% in the control group; p = 0.003). Significantly more patients with a fungating tumor underwent amputation (35% compared with 12% in the control group; p = 0.01), while a greater proportion of control patients received radiation therapy (68% compared with 39% in the group with a fungating tumor; p = 0.02). There was no difference in the proportions of patients receiving chemotherapy or in the local recurrence rates between the two cohorts. The Kaplan-Meier five-year overall survival estimates were 20% in the group with a fungating tumor compared with 63% (p < 0.0001) in the control group. The Kaplan-Meier five-year disease-specific survival estimates for patients presenting with localized disease was 58% in the group with a fungating tumor and 74% in the control group (p = 0.05). Multivariate analysis demonstrated that disease stage, fungation, and a tumor size of > or = 10 cm were significant independent negative prognostic factors for disease-specific survival. CONCLUSIONS: Malignant tumor ulceration is an independent predictor of a poor prognosis for patients with a high-grade soft-tissue sarcoma. Despite the discouraging overall prognosis, aggressive multidisciplinary treatment can lead to long-term survival in an important subgroup of patients with fungating lesions.

Extraskeletal para-articular osteochondroma of the posterior knee.

Extraskeletal para-articular osteochondromas are unusual osteocartilaginous lesions that arise in the soft tissues adjacent to the joint with no bone or joint continuity. This diagnosis should be considered in patients with a well-circumscribed, extraskeletal, mineralized mass without any direct continuity with adjacent bone or joint. Although the knee is a common location for extraskeletal para-articular osteochondroma, it has not been described arising in the posterior aspect of the knee. This article presents a case of extraskeletal paraarticular osteochondroma posterior to the knee joint. Differentiation from other extraskeletal mineralized lesions, particularly extraskeletal sarcomas and synovial osteochondromatosis, is essential to avoid unnecessary aggressive surgical procedures as marginal excision is adequate for these lesions. Correlation of clinical and radiographic features with pathology is essential for diagnosis. The lesion in our patient was marginally excised, and the postoperative course was uneventful with no recurrence at 2-year follow-up.

IL-17 disrupts corneal barrier following desiccating stress.

T helper (Th)-17 is a recently identified subtype of Th response that has been implicated in host defense and autoimmunity. We investigated whether there is evidence for a Th-17 response in human and experimental murine dry eye (DE). Gene expression in the human DE conjunctiva showed increased levels of the Th-17 inducers, interleukin (IL)-23, IL-17A, and interferon-gamma (IFN-gamma). In the murine model, we found that desiccating stress increased matrix metalloproteinase-9, Th-17-associated genes (IL-6, IL-23, transforming growth factor-beta1 and -2, IL-23R, IL-17R, IL-17A, retinoid-related orphan receptor-gammat, and CC chemokine attractant ligand-20) and IFN-gamma in cornea and conjunctiva. Furthermore, we found a significantly increased concentration of IL-17 in tears and number of IL-17-producing cells on the ocular surface. Antibody neutralization of IL-17 ameliorated experimental DE-induced corneal epithelial barrier dysfunction and decreased the expression of matrix metalloproteinases 3 and 9. Taken together, these findings suggest that IL-17 has a role in corneal epithelial barrier disruption in DE.

Extended intralesional treatment versus resection of low-grade chondrosarcomas.

UNLABELLED: The need for segmental resection versus intralesional treatment of low-grade chondrosarcomas of the appendicular skeleton remains controversial. We hypothesized extended intralesional treatment would equally control malignant disease but with improved functional outcomes and decreased postoperative complications. We retrospectively reviewed 31 patients with 32 Grade I intracompartmental chondrosarcomas of the long bones of the appendicular skeleton treated with either resection (15 lesions) or extended intralesional curetting (17) at a minimum followup of 2 years (median, 55 months; range, 24-203 months). Lesions were larger and median followup was longer in the resection cohort. One local recurrence developed in each treatment cohort and neither transitioned to a higher grade of tumor. No patient had metastases develop or died of disease. The mean final Musculoskeletal Tumor Society functional scores were greater after extended intralesional versus resection treatment (29.5 versus 25.1). Complications were observed more frequently after resection and reconstruction (seven of 15) as compared with extended intralesional treatment (one of 17). Extended intralesional treatment of Grade I intracompartmental chondrosarcomas of the long bones of the appendicular skeleton therefore appears safe with improved functional scores and decreased complications versus segmental resection and reconstruction. LEVEL OF EVIDENCE: Level III, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

Cystic presentation of Ewing's sarcoma with indolent clinico-radiologic behaviour.

Ewing's sarcoma is a high-grade malignant primary bone tumour with aggressive clinico-radiologic features. Rarely, it exhibits a benign pattern, but presentation as a solitary bone cyst in a long bone is rather unusual. The purpose of this paper is to document such a cystic presentation with relatively benign clinico-radiologic course and to review the pertinent literature. A 27-year-old male presented with a pathologic fracture through a radiologically benign appearing solitary bone cyst in the distal tibial metaphysis. The fracture healed on conservative treatment, but the patient presented again a year later with pain and difficulty with weight bearing. Curetting and bone grafting done elsewhere was suggestive of an Ewing's sarcoma, which was later confirmed by a second biopsy. He was treated by standard neoadjuvant chemotherapy followed by wide local excision and reconstruction with an intercalary allograft. At 2 years postoperative follow-up, the patient is without any evidence of local or distant recurrence. Awareness of this atypical presentation is important because it may help in an earlier diagnosis, avoid diagnostic confusion and thus may contribute to improved survival.

Proximal humerus reconstructions for tumors.

UNLABELLED: The optimal method for reconstructing the proximal humerus in patients with tumors is controversial. To determine functional outcomes and complication rates after different types of reconstructions, we reviewed a consecutive series of 49 patients who underwent proximal humerus resection and osteoarticular allograft (17 patients), allograft-prosthetic composite (16), or endoprosthetic (16) reconstruction. Operative indications included primary malignancies (24 patients), metastatic disease (19), and benign aggressive disease (six). Implant revision was more common after osteoarticular reconstruction (five of 17) than after allograft-prosthetic composite (one of 16) or endoprosthetic (zero of 16) reconstructions. At a minimum followup of 24 months (median, 98 months; range, 24-214 months) in surviving patients, Musculoskeletal Tumor Society functional scores averaged 79% for the allograft-prosthetic composite, 71% for the osteoarticular allograft, and 69% for the endoprosthetic reconstruction cohorts. Shoulder instability was associated with abductor mechanism compromise and was more common after endoprosthetic reconstruction. Allograft fractures occurred in 53% of patients receiving osteoarticular allografts. We recommend allograft-prosthetic composite reconstruction for younger patients with primary tumors of bone and endoprosthetic reconstruction for older patients with metastatic disease. Because of the unacceptable complication rate, we do not recommend osteoarticular allograft reconstruction for routine use in the proximal humerus. LEVEL OF EVIDENCE: Level III, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.