Marine Monitoring Program: Annual Report for inshore pesticide monitoring 2018–19

[Extract] This component of the Marine Monitoring Program provides an understanding of nearshore pesticide profiles and the exposure risk to marine organisms, as a part of water quality condition on the Great Barrier Reef. Data are collected from eleven fixed monitoring sites located in four Natural Resource Management regions — the Wet Tropics (five sites: Low Isles, High Island, Normanby Island, Dunk Island and Lucinda), Burdekin (one site: Barratta Creek), Mackay-Whitsundays (four sites: Repulse Bay, Flat Top Island, Sandy Creek and Sarina Inlet) and Fitzroy (one site: North Keppel Island). The suite of pesticides monitored includes photosystem II (PSII) inhibiting herbicides (such as diuron, atrazine (and its metabolites), ametryn, hexazinone, tebuthiuron), which all affect photosynthesis, and are commonly detected due to their high usage in adjacent catchments, and their high solubility. Other pesticides monitored include those that have non-photosynthetic effects (such as imidacloprid and metolachlor) and knockdown herbicides (such as 2,4-D)

Lung recurrence of papillary thyroid cancer diagnosed with antithyroglobulin antibodies after 10 years from initial treatment.

Introduction: Papillary thyroid cancer (PTC) is the most common endocrine malignancy. More than 98% of patients achieve an excellent response with no evidence of clinical, biochemical, or structural disease after initial treatment. In these patients structural recurrence is rare, more frequently diagnosed in the first 5 years from initial treatment and almost invariably localized in neck lymph nodes. Patient: We report the case of a woman affected by PTC who presented with rapidly rising anti-thyroglobulin antibodies (TgAb) level after 10 years from clinical, morphological and biochemical remission. Diagnosis and Treatment: In 2003, a 56 year old patient was treated with total thyroidectomy and radioiodine remnant ablation (RRA) for a PTC (2 cm) with minimal extrathyroidal extension (T3N1aM0 according to the 6th AJCC TNM staging system) associated with diffuse lymphocytic thyroiditis. In 2004 the patient was free of disease defined as undetectable Tg after recombinant human TSH administration in the absence of TgAb and structural disease. Since February 2012 the appearance and progressive increase of TgAb titer was observed and in 2014 a18FDG-PET scan documented three hypermetabolic lesions suggestive of lung micrometastases. The lung lesions were cytologically confirmed as PTC metastases. Both the primary tissue and the lung metastasis were positive for BRAF V600E mutation. The patient was treated with 131-radioiodine that showed radioiodine avid lung lesions that lose the ability to take up iodine at the following treatment. The patient is still alive and the lung lesions are growing slowly. Conclusions: Structural recurrence in patients that demonstrated an excellent response after initial treatment for PTC is extremely rare, and distant metastases exceptional but possible. This case is peculiar because recurrence was early identified after 10 years from initial treatment for the presence of detectable TgAb in a patient that had an histological diagnosis of lymphocytic thyroiditis but with an atypical clinical presentation (normal thyroid at neck ultrasound and undetectable TgAb and anti-thyroid peroxidase antibodies). For this reason TgAb should be tested with Tg in patients with a history of lymphocytic thyroiditis, either histological or humoral, also when TgAb is in the normal range and not suggestive of autoimmune thyroiditis

Breast Cancer After Treatment of Differentiated Thyroid Cancer With Radioiodine in Young Females: What We Know and How to Investigate Open Questions. Review of the Literature and Results of a Multi-Registry Survey

Published studies on the risk of radiation-induced second primary malignancy (SPM) after radioiodine treatment (RAI) of differentiated thyroid cancer (DTC) refer mainly to patients treated as middle-aged or older adults and are not easily generalizable to those treated at a younger age. Here we review available literature on the risk of breast cancer as an SPM after RAI of DTC with a focus on females undergoing such treatment in childhood, adolescence, or young adulthood. Additionally, we report the results of a preliminary international survey of patient registries from academic tertiary referral centers specializing in pediatric DTC. The survey sought to evaluate the availability of sufficient patient data for a potential international multicenter observational case–control study of females with DTC given RAI at an early age. Our literature review identified a bi-directional association of DTC and breast cancer. The general breast cancer risk in adult DTC survivors is low, ~2%, slightly higher in females than in males, but presumably lower, not higher, in those diagnosed as children or adolescents than in those diagnosed at older ages. RAI presumably does not substantially influence breast cancer risk after DTC. However, data from patients given RAI at young ages are sparse and insufficient to make definitive conclusions regarding age dependence of the risk of breast cancer as a SPM after RAI of DTC. The preliminary analysis of data from 10 thyroid cancer registries worldwide, including altogether 6,449 patients given RAI for DTC and 1,116 controls, i.e., patients not given RAI, did not show a significant increase of breast cancer incidence after RAI. However, the numbers of cases and controls were insufficient to draw statistically reliable conclusions, and the proportion of those receiving RAI at the earliest ages was too low.In conclusion, a potential international multicenter study of female patients undergoing RAI of DTC as children, adolescents, or young adults, with a sufficient sample size, is feasible. However, breast cancer screening of a larger cohort of DTC patients is not unproblematic for ethical reasons, due to the likely, at most slightly, increased risk of breast cancer post-RAI and the expected ~10% false-positivity rate which potentially produced substantial “misdiagnosis.

Correlative analyses of RET and RAS mutations in a phase 3 trial of cabozantinib in patients with progressive, metastatic medullary thyroid cancer

BACKGROUND: Cabozantinib significantly prolonged progression-free survival (PFS) versus a placebo in patients with progressive, metastatic medullary thyroid cancer (MTC; P <.001). An exploratory analysis of phase 3 trial data evaluated the influence of rearranged during transfection (RET) and RAS (HRAS, KRAS, and NRAS) mutations on cabozantinib clinical activity. METHODS: Patients (n = 330) were randomized to cabozantinib (140 mg/day) or a placebo. The primary endpoint was PFS. Additional outcome measures included PFS, objective response rates (ORRs), and adverse events in RET and RAS mutation subgroups. RESULTS: Among all study patients, 51.2% were RET mutation–positive (38.2% with RET M918T), 34.8% were RET mutation–unknown, and 13.9% were RET mutation–negative. Sixteen patients were RAS mutation–positive. Cabozantinib appeared to prolong PFS versus the placebo in the RET mutation–positive subgroup (hazard ratio [HR], 0.23; 95% confidence interval [CI], 0.14-0.38; P <.0001), the RET mutation–unknown subgroup (HR, 0.30; 95% CI, 0.16-0.57; P =.0001), and the RAS mutation–positive subgroup (HR, 0.15; 95% CI, 0.02-1.10; P =.0317). The RET M918T subgroup achieved the greatest observed PFS benefit from cabozantinib versus the placebo (HR, 0.15; 95% CI, 0.08-0.28; P <.0001). The ORRs for RET mutation–positive, RET mutation–negative, and RAS mutation–positive patients were 32%, 22%, and 31%, respectively. No PFS benefit was observed in patients lacking both RET and RAS mutations, although the ORR was 21%. The safety profile for all subgroups was similar to that for the overall cabozantinib arm. CONCLUSIONS: These data suggest that cabozantinib provides the greatest clinical benefit to patients with MTC who have RET M918T or RAS mutations. However, a prospective trial is needed to confirm the relation between genetic variation and the response to cabozantinib. Cancer 2016;122:3856–3864. © 2016 American Cancer Society

The Nylon Scintillator Containment Vessels for the Borexino Solar Neutrino Experiment

Borexino is a solar neutrino experiment designed to observe the 0.86 MeV Be-7 neutrinos emitted in the pp cycle of the sun. Neutrinos will be detected by their elastic scattering on electrons in 100 tons of liquid scintillator. The neutrino event rate in the scintillator is expected to be low (~0.35 events per day per ton), and the signals will be at energies below 1.5 MeV, where background from natural radioactivity is prominent. Scintillation light produced by the recoil electrons is observed by an array of 2240 photomultiplier tubes. Because of the intrinsic radioactive contaminants in these PMTs, the liquid scintillator is shielded from them by a thick barrier of buffer fluid. A spherical vessel made of thin nylon film contains the scintillator, separating it from the surrounding buffer. The buffer region itself is divided into two concentric shells by a second nylon vessel in order to prevent inward diffusion of radon atoms. The radioactive background requirements for Borexino are challenging to meet, especially for the scintillator and these nylon vessels. Besides meeting requirements for low radioactivity, the nylon vessels must also satisfy requirements for mechanical, optical, and chemical properties. The present paper describes the research and development, construction, and installation of the nylon vessels for the Borexino experiment

A New MEN2 Syndrome with Clinical Features of Both MEN2A and MEN2B Associated with a New RET Germline Deletion

Background. Multiple endocrine neoplasia type 2 (MEN2) is a hereditary cancer syndrome caused by RET proto-oncogene mutation. Two different clinical variants of MEN2 are known (MEN2A and MEN2B): medullary thyroid carcinoma (MTC) almost always present and associated with pheochromocytoma (Pheo), and primary hyperparathyroidism (HPTH) in MEN2A and with Pheo and other nonendocrine diseases in MEN2B. Case Report. A 7-year-old girl, previously treated for a pelvic plexiform neurofibroma, arrived at our observation with a peculiar MEN2B syndrome and with HPTH. The neck ultrasound showed bilateral thyroid nodules, local lymph node lesions, and a suspicious left hyperplastic parathyroid. The CT scan showed a megacolon and described the persistence of the pelvic tumor. A new RET germline deletion in exon 11 (c.1892_1899delCGAGCT; p.Glu632_Leu633del) was found. She underwent total thyroidectomy, central compartment and latero-cervical lymph node dissection, and neck exploration for primary HPTH. The histology confirmed bilateral MTC, multiple lymph node metastases, a hyperplastic parathyroid, and a parathyroid adenoma. Conclusions. This is the first case of a complex syndrome characterized by peculiar features of MEN2B, without Pheo but with a pelvic plexiform neurofibroma and with HPTH, which is typical of MEN2A. A "de novo"new germline RET deletion located in exon 11 was found

IgG and IgG2 antibodies from cattle naturally infected with Anaplasma marginale recognize the recombinant vaccine candidate antigens VirB9, VirB10, and elongation factor-Tu.

Anaplasma marginale is an important vector-borne rickettsia of ruminants in tropical and subtropical regions of the world. Immunization with purified outer membranes of this organism induces protection against acute anaplasmosis. Previous studies, with proteomic and genomic approach identified 21 proteins within the outer membrane immunogen in addition to previously characterized major surface protein1a-5 (MSP1a-5). Among the newly described proteins were VirB9, VirB10, and elongation factor-Tu (EF-Tu). VirB9, VirB10 are considered part of the type IV secretion system (TFSS), which mediates secretion or cell-to-cell transfer of macromolecules, proteins, or DNA-protein complexes in Gram-negative bacteria. EF-Tu can be located in the bacterial surface, mediating bacterial attachment to host cells, or in the bacterial cytoplasm for protein synthesis. However, the roles of VirB9, VirB10, and TFSS in A. marginale have not been defined. VirB9, VirB10, and EF-Tu have not been explored as vaccine antigens. In this study, we demonstrate that sera of cattle infected with A. marginale, with homologous or heterologous isolates recognize recombinant VirB9, VirB10, and EF-Tu. IgG2 from naturally infected cattle also reacts with these proteins. Recognition of epitopes by total IgG and by IgG2 from infected cattle with A. marginale support the inclusion of these proteins in recombinant vaccines against this rickettsia

New results on solar neutrino fluxes from 192 days of Borexino data

We report the direct measurement of the ^7Be solar neutrino signal rate performed with the Borexino detector at the Laboratori Nazionali del Gran Sasso. The interaction rate of the 0.862 MeV ^7Be neutrinos is 49+-3(stat)+-4(syst) counts/(day * 100ton). The hypothesis of no oscillation for ^7Be solar neutrinos is inconsistent with our measurement at the 4sigma level. Our result is the first direct measurement of the survival probability for solar nu_e in the transition region between matter-enhanced and vacuum-driven oscillations. The measurement improves the experimental determination of the flux of ^7Be, pp, and CNO solar nu_e, and the limit on the magnetic moment of neutrinos

New limits on nucleon decays into invisible channels with the BOREXINO Counting Test Facility

The results of background measurements with the second version of the BOREXINO Counting Test Facility (CTF-II), installed in the Gran Sasso Underground Laboratory, were used to obtain limits on the instability of nucleons, bounded in nuclei, for decays into invisible channels ($inv$): disappearance, decays to neutrinos, etc. The approach consisted of a search for decays of unstable nuclides resulting from $N$ and $NN$ decays of parents $^{12}$C, $^{13}$C and $^{16}$O nuclei in the liquid scintillator and the water shield of the CTF. Due to the extremely low background and the large mass (4.2 ton) of the CTF detector, the most stringent (or competitive) up-to-date experimental bounds have been established: $\tau(n \to inv) > 1.8 \cdot 10^{25}$ y, $\tau(p \to inv) > 1.1 \cdot 10^{26}$ y, $\tau(nn \to inv) > 4.9 \cdot 10^{25}$ y and $\tau(pp \to inv) > 5.0 \cdot 10^{25}$ y, all at 90% C.L.Comment: 22 pages, 3 figures,submitted to Phys.Lett.