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.

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.

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.

Role of beta gamma subunits of G proteins in targeting the beta-adrenergic receptor kinase to membrane-bound receptors.

The rate and extent of the agonist-dependent phosphorylation of beta 2-adrenergic receptors and rhodopsin by beta-adrenergic receptor kinase (beta ARK) are markedly enhanced on addition of G protein beta gamma subunits. With a model peptide substrate it was demonstrated that direct activation of the kinase could not account for this effect. G protein beta gamma subunits were shown to interact directly with the COOH-terminal region of beta ARK, and formation of this beta ARK-beta gamma complex resulted in receptor-facilitated membrane localization of the enzyme. The beta gamma subunits of transducin were less effective at both enhancing the rate of receptor phosphorylation and binding to the COOH-terminus of beta ARK, suggesting that the enzyme preferentially binds specific beta gamma complexes. The beta gamma-mediated membrane localization of beta ARK serves to intimately link receptor activation to beta ARK-mediated desensitization.

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.

Consequences and prevention of inadvertent internal fixation of primary osseous sarcomas.

UNLABELLED: The evaluation and treatment of aggressive bone tumors continue to be diagnostic and therapeutic challenges for orthopaedic surgeons. Despite compelling data regarding the hazards of biopsy, incomplete preoperative evaluation, inappropriate biopsy techniques, and premature surgical interventions continue to compromise optimal treatment of primary bone sarcomas. We retrospectively identified eight patients who had internal fixation of a primary bone sarcoma before referral to an orthopaedic oncology service. Six of the eight patients subsequently underwent amputations and two patients underwent limb salvage for local disease control. Biopsy techniques from referring institutions were highly variable, with only two of seven rendering an accurate diagnosis. The average Musculoskeletal Tumor Society functional score was 10.6 and four of eight patients were disease-free and alive at a minimum followup of 8 months (mean, 26.9 months; range, 8-80 months). Implant violation of primary bone malignancies was associated with frequent high-level amputation for local disease control and low Musculoskeletal Tumor Society functional scores. Common errors in the initial evaluation and treatment included inadequate attention to patient history, incomplete radiographic evaluation, and improper biopsy and surgical techniques, which violated compartmental boundaries. LEVEL OF EVIDENCE: Level IV, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence.

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.

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.

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.

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.

Local recurrence of disease after unplanned excisions of high-grade soft tissue sarcomas.

UNLABELLED: Unplanned excisions of soft tissue sarcomas occur with alarming frequency and result in high rates of residual disease, potentially affecting patient prognosis. To determine if unplanned excisions and residual disease status at tumor bed excision increased local recurrence rates and predicted disease-specific patient survival, we retrospectively reviewed 203 consecutive patients with high-grade soft tissue sarcomas treated operatively and followed for at least 2 years (mean, 4.8 years) or until patient death. Among the 64 patients (32%) who had undergone previous unplanned excisions, six had gross residual disease and 40 of the remaining 58 (69%) had microscopic residual disease in the tumor bed. We observed subsequent local recurrence in nine of the 139 patients (6%) after planned excision compared with 22 patients (34%) after unplanned excision. More patients with unplanned excisions who underwent limb salvage procedures required flap coverage and/or skin grafting with their definitive resection (30% versus 5%). In the unplanned excision cohort, residual disease status at tumor bed excision predicted increased rates of local recurrence and decreased disease-specific survival. Unplanned excisions of high-grade soft tissue sarcomas resulted in increased rates of local recurrence but not disease-specific survival. Residual disease at reexcision predicted the likelihood of local recurrence. LEVEL OF EVIDENCE: Level II, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence.

Soft tissue sarcomas of the foot and ankle: impact of unplanned excision, limb salvage, and multimodality therapy.

BACKGROUND: Foot and ankle sarcomas have historically been treated with amputation because of the difficulty in achieving local disease control and maintaining a functional foot. Potential opportunities for limb salvage may be further compromised by unplanned excisions. MATERIALS AND METHODS: We reviewed 52 consecutive patients with soft tissue sarcomas of the foot and ankle and analyzed the impact of planned versus unplanned initial excision, limb salvage, and multimodality therapy on treatment and outcomes. RESULTS: Unplanned excisions had been performed in 29 (55.8%) patients. Limb salvage was performed in 38 patients, with 14 requiring free soft tissue transfers. At an average followup of 99 (range, 24 to 216) months, the 5-year overall survival estimate was 76.3%. Although not statistically significant, we noted clinically relevant potential differences in local recurrence-free, disease-free, and oncologic survival between the planned and unplanned excision groups. Seven patients (13.5%) had a local recurrence, five of these following an unplanned excision. Functional scores averaged 83.2% for all patients which were similar between planned versus unplanned and amputation versus limb salvage groups. Significantly more patients with unplanned excisions required free flaps for limb salvage (p = 0.017) and received adjuvant radiotherapy (p = 0.0004). CONCLUSION: Unplanned surgery for soft tissue sarcomas of the foot and ankle often results in the need for more aggressive surgery and/or adjuvant radiotherapy and may impact oncologic outcomes, but does not necessarily portend worse functional outcomes. Multimodal therapy and judicious use of soft tissue flap reconstruction allows limb salvage in most patients with favorable outcomes.

Metastatic skeletal disease of the foot: case reports and literature review.

BACKGROUND: Metastatic disease of the skeleton occurs in at least 20% to 30% of patients with malignancy, but metastasis to the foot and hand (acrometastasis) is extremely rare (0.007% to 0.3%). Metastases to the feet are even rarer and have been reported in half to one-third the rate for hand metastases. Failure to recognize these lesions has led to delayed diagnosis and/or inappropriate treatment. The purpose of this report is to highlight the clinical and radiologic features that aid in the diagnosis and potential treatment of this condition along with a pertinent review of the literature. MATERIALS AND METHODS: In a retrospective review of 694 patients with histologically proven metastatic skeletal disease (January 1988 to January 2007), 14 cases of metastatic lesions to the foot were identified. RESULTS: The most frequent primary site was in the genito-urinary system in eight patients and the most common bones involved were the calcaneus and the talus in six patients each. All patients died after a mean survival of 14.8 (range, 1 to 54) months after diagnosis of metastases. CONCLUSION: Although metastatic disease of the foot is rare, it should be considered in the diagnosis of a painful foot, especially if suspicious radiographic changes are present in an older patient. The common primary sites are the genito-urinary, lungs, breast, and the colo-rectum. Treatment is usually palliative to reduce pain and maintain function.

Pigmented villonodular bursitis/diffuse giant cell tumor of the pes anserine bursa: a report of two cases and review of literature.

Pigmented villonodular synovitis (PVNS) is a benign but potentially aggressive lesion, characterized by synovial villonodular proliferation with hemosiderin pigmentation and stromal infiltration of histiocytes and giant cells. This consists of a common family of lesions, including localized and diffuse forms of pigmented villonodular synovitis, giant cell tumor of the tendon sheath (nodular tenosynovitis) and the very rare cases of extra-articular pigmented villonodular synovitis arising from the bursa (pigmented villonodular bursitis or diffuse giant cell tumor of the tendon sheath). The purpose of this paper is to present two rare cases of pigmented villonodular bursitis arising from the pes anserinus bursa. The various differentials along with a review of literature of similar lesions are also being discussed. However, as with other lesions, clinicoradiographic features along with close histological correlation is essential for diagnosis.

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.

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.

The radiographic morphology of foot deformities in patients with fibrodysplasia ossificans progressiva.

BACKGROUND: The most consistent deformities that allow early diagnosis of fibrodysplasia ossificans progressiva are the presence of bilateral short first rays and hallux valgus. The purpose of this study was to describe the radiographic features observed in the feet of patients with fibrodysplasia ossificans progressiva. METHODS: The radiographs of 26 feet (15 patients with fibrodysplasia ossificans progressiva) were reviewed to evaluate the radiographic changes that occur in the first ray. Variables analyzed were the hallux valgus (HV) angle, the distal metatarsal articular (DMA) angle, the proximal phalangeal articular (PPA) angle, the intermetatarsal (IM) angle, ratio of the lengths of the first and second metatarsal lengths (MT1:MT2), and the first and second ray length ratio. The length ratios were then subtracted from similar ratios in radiographs of age- and gender-matched normal patients previously reported. RESULTS: The proximal phalanx was consistently shortened but morphologically dissimilar from subject to subject. Asymmetry was noted in some patients with bilateral radiographs. The mean HV angle was 28 degrees, and the mean IM angle was 10 degrees. The mean DMA angle was 33 degrees, and the mean PPA angle was 14 degrees. The MT1:MT2 ratio was 0.89, and the mean first ray to second ray length ratio was 0.87. The mean of the differences in the MT1:MT2 and first and second ray length ratios in patients with fibrodysplasia ossificans progressiva compared to the normal controls were 0.05 and 0.01, respectively. Fusion occurred between the abnormal tibial epiphysis of the proximal phalanx and metatarsal head with advancing age, and 68% of the metatarsal heads were fused with the abnormal proximal phalangeal epiphysis. CONCLUSIONS: Foot pathology in patients with fibrodysplasia ossificans progressiva is variable but consistently involves an abnormality of the tibial aspect of the proximal phalangeal epiphysis of the hallux. This results in the clinical observation of hallux valgus in these patients. The first metatarsal is consistently shortened, and fusion between the epiphysis of the abnormal proximal phalanx and the shortened first metatarsal head occurs with advancing age.

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.