Fishing safely during COVID-19 in Newfoundland and Labrador, Canada: Making it happen.

Globally, fisheries have been the site of multiple documented outbreaks of COVID-19. Existing studies point to the threat posed by the pandemic to livelihoods and health among migrant industrial fishery workers, small-scale fish harvesters, and fishing communities. They show the pandemic enhanced safety, economic, social and political layers of vulnerability in fisheries, while also showcasing examples of resilience. Case studies of COVID-19 response provide an opportunity to explore how existing organizational structures, leadership and networks in fisheries can enable the rapid co-development of customized strategies for fishing safely during large-scale global disruptions such as pandemics. This article contributes to our understanding of governance and fishing safety in small-scale fisheries during the early pandemic, examining the response of small-scale fisheries in the Canadian province of Newfoundland and Labrador. These seasonal fisheries successfully opened with regulator approval after a short delay and operated without documented COVID-19 outbreaks during 2020. Findings draw from key informant interviews with a safety sector association and union leader, complemented with insights from an anonymous online survey of small-scale harvesters. Interviews capture the organizational processes and resources mobilized to rapidly co-develop the COVID-19 Safe Work Practice Guideline. Online survey findings indicate that fifty-nine percent of respondents (crew and skippers) had no COVID-19-related concerns while fishing in 2020; older harvesters and owner-operators were significantly more likely to indicate concerns. When asked about the relative practicality of listed COVID-19 precautions, respondents commonly identified sanitization, reduced interactions with shore workers, social distancing, protection equipment, modifications to eating/rest areas, and reduced crew as impractical. These assessments are generally consistent with those of the interviewed leaders and the Guideline approach. This suggests the co-developed Guideline provided tailored and practical COVID-19 prevention strategies. Pre-existing governance structures and networks can help address small-scale fisheries vulnerabilities to pandemics by supporting co-development of organizational resources and evidence-informed prevention strategies.

Iridium(III) bis(thiophosphinite) pincer complexes: synthesis, ligand activation and applications in catalysis.

Iridium(III) bis(thiophosphinite) complexes of the type [(RPSCSPR)Ir(H)(Cl)(py)] (RPSCSPR = κ3-(2,6-SPR2)C6H3) (R = tBu, iPr, Ph) can be prepared from the ligand precursors 1,3-(SPR2)C6H4 by C-H activation at Ir using [Ir(COE)2Cl]2 or [Ir(COD)Cl]2. Optimisation of the protocol for complexation showed that direct cyclometallation in the absence or presence of pyridine, as well as C-H activation in the presence of H2 are viable options that, depending on the phosphine substituent furnish the five-coordinate Ir(III) hydride chloride complexes 2-R or the base stabilised species 3-R in good yields. In case of the PhPSCSPPh ligand, P-S activation results in the formation of a thiophosphine stabilised Ir(III) hydride complex [(PhPSCSPPh)Ir(H)(Cl)(PPh2SH)] (4). Reaction of 2-tBu with H2 in the presence of base furnishes an Ir(III) dihydride complex (5) via a labile Ir(III) dihydride-dihydrogen complex (6). All complexes are inactive for transfer dehydrogenation of cyclooctane in the presence of NaOtBu and tert-butylethylene, likely due to decomposition of the Ir complex in the presence of base at higher temperature.

Synthesis and fluorosolvatochromism of 3-arylnaphtho[1,2-b]quinolizinium derivatives.

Cationic biaryl derivatives were synthesized by Suzuki-Miyaura coupling of 3-bromonaphtho[1,2-b]quinolizinium bromide with arylboronic acids. The resulting cationic biaryl derivatives exhibit pronounced fluorosolvatochromic properties. First photophysical studies in different solvents showed that the emission energy of the biaryl derivatives decreases with increasing solvent polarity. This red-shifted emission in polar solvents is explained by a charge shift (CS) in the excited state and subsequent solvent relaxation. Furthermore, the polarity of protic polar and aprotic polar solvents affects the emission energy to different extent, which indicates a major influence of hydrogen bonding on the stabilization of the ground and excited states.

The Effects of Clinically Relevant Hypertonic Saline and Conivaptan Administration on Ischemic Stroke.

Cerebral edema after stroke is associated with poor neurological outcomes. Current therapies are limited to osmotic agents, such as hypertonic saline (HS), which reduce intracranial pressure. Although studies have demonstrated edema reductions following HS, tissue survival has not been thoroughly examined. Additionally, the efficacy of promising pharmacological agents has not been evaluated for synergy with osmotic agents. Conivaptan is an FDA-approved vasopressin receptor antagonist that may exert both osmotic and anti-inflammatory effects. In this study, rats were subjected to middle cerebral artery occlusion prior to treatment with 5 % HS bolus +5 % HS maintenance (HS), conivaptan alone (Con), conivaptan +5 % HS maintenance (Con + HS), or conivaptan +5 % HS bolus +5 % maintenance (Con + HSb). Treatments were initiated at six (Early) or 24 h (Late) following stroke and rats were euthanized at 48 h to evaluate infarct volume, brain edema, and microglia/macrophage activation. Infarct volume and brain edema in the Early HS, Early Con, and Late HS groups were significantly reduced compared with controls. Interestingly, only the Early Con group demonstrated reduced microglia/macrophage activation. These data suggest an anti-inflammatory mechanism for conivaptan and provide support for a multipronged approach combining osmotic agents with compounds that inhibit the neuroinflammatory response to stroke.

Gold nanoparticle-enabled blood test for early stage cancer detection and risk assessment.

When citrate ligands-capped gold nanoparticles are mixed with blood sera, a protein corona is formed on the nanoparticle surface due to the adsorption of various proteins in the blood to the nanoparticles. Using a two-step gold nanoparticle-enabled dynamic light scattering assay, we discovered that the amount of human immunoglobulin G (IgG) in the gold nanoparticle protein corona is increased in prostate cancer patients compared to noncancer controls. Two pilot studies conducted on blood serum samples collected at Florida Hospital and obtained from Prostate Cancer Biorespository Network (PCBN) revealed that the test has a 90-95% specificity and 50% sensitivity in detecting early stage prostate cancer, representing a significant improvement over the current PSA test. The increased amount of human IgG found in the protein corona is believed to be associated with the autoantibodies produced in cancer patients as part of the immunodefense against tumor. Proteomic analysis of the nanoparticle protein corona revealed molecular profile differences between cancer and noncancer serum samples. Autoantibodies and natural antibodies produced in cancer patients in response to tumorigenesis have been found and detected in the blood of many cancer types. The test may be applicable for early detection and risk assessment of a broad spectrum of cancer. This new blood test is simple, low cost, requires only a few drops of blood sample, and the results are obtained within minutes. The test is well suited for screening purpose. More extensive studies are being conducted to further evaluate and validate the clinical potential of the new test.

Rapid onset of guillain-barré syndrome after an obstetric epidural block.

Reports of acute onset of Guillain-Barré syndrome (GBS) after epidural anesthesia/analgesia after labor and cesarean delivery has raised concern of a correlation between GBS and the use of neuraxial anesthesia. We present a patient who developed bilateral lower extremity weakness and paraparesis within hours after removal of an epidural catheter for cesarean delivery. The clinical diagnosis was highly suggestive for GBS after magnetic resonance imaging, cerebrospinal fluid findings, electromyogram, and nerve conduction studies. We discuss the pathophysiological mechanisms suggested in previous case reports and describe the relationship between epidural analgesia and GBS.

Effects of vaginal estrogens on serum estradiol levels in postmenopausal breast cancer survivors and women at risk of breast cancer taking an aromatase inhibitor or a selective estrogen receptor modulator.

BACKGROUND: Intravaginal estradiols (VE) have been proposed as safe alternatives to systemic estrogen therapy in breast cancer survivors. PATIENTS AND METHODS: Postmenopausal women with estrogen receptor-positive breast cancer or at high risk for breast cancer (n = 24) who were taking an aromatase inhibitor (AI) or a selective estrogen receptor modulator (SERM) and VE for ≥ 90 days for atrophic vaginitis and 24 controls taking AI only participated in the study. Serum samples were drawn from VE ring patients before insertion and 30 and 60 days postinsertion, from VE tablet patients the morning before insertion and approximately 12 hours postinsertion, and once from controls. Samples were assayed for E2 concentrations by using highly sensitive radioimmunoassay after ether extraction. RESULTS: Mean E2 levels in controls were 3.72 pmol/L (range, < 3.0-7.7 pmol/L); mean E2 levels preinsertion and 12 weeks postinsertion in the VE ring patients were significantly greater than controls (P < .001 for each comparison). Mean preinsertion E2 levels in patients using VE tablets were not significantly different than those of controls (P = .48), and postinsertion levels were 76 pmol/L higher than preinsertion (P < .001). CONCLUSION: VE treatment increased E2 levels. Preinsertion levels for patients receiving VE tablets were not elevated compared with those of controls, suggesting that E2 elevations with this preparation may not be continuously sustained. We conclude that VE treatment, regardless of type, results in elevated circulating E2 levels in this population and should be used with caution.

Developing a nanoparticle test for prostate cancer scoring.

BACKGROUND: Over-diagnosis and treatment of prostate cancer has been a major problem in prostate cancer care and management. Currently the most relevant prognostic factor to predict a patient's risk of death due to prostate cancer is the Gleason score of the biopsied tissue samples. However, pathological analysis is subjective, and the Gleason score is only a qualitative estimate of the cancer malignancy. Molecular biomarkers and diagnostic tests that can accurately predict prostate tumor aggressiveness are rather limited. METHOD: We report here for the first time the development of a nanoparticle test that not only can distinguish prostate cancer from normal and benign conditions, but also has the potential to predict the aggressiveness of prostate cancer quantitatively. To conduct the test, a prostate tissue lysate sample is spiked into a blood serum or human IgG solution and the spiked sample is incubated with a citrate-protected gold nanoparticle solution. IgG is known to adsorb to citrate-protected gold nanoparticles to form a "protein corona" on the nanoparticle surface. From this study, we discovered that certain tumor-specific molecules can interact with IgG and change the adsorption behavior of IgG to the gold nanoparticles. This change is reflected in the nanoparticle size of the assay solution and detected by a dynamic light scattering technique. Assay data were analyzed by one-way ANOVA for multiple variant analysis, and using the Student t-test or nonparametric Mann-Whitney U-tests for pairwise analyses. RESULTS: An inverse, quantitative correlation of the average nanoparticle size of the assay solution with tumor status and histological diagnostic grading was observed from the nanoparticle test. IgG solutions spiked with prostate tumor tissue exhibit significantly smaller nanoparticle size than the solutions spiked with normal and benign tissues. The higher grade the tumor is, the smaller the nanoparticle size is. The test particularly revealed large differences among the intermediate Grade 2 tumors, and suggested the need to treat them differently. CONCLUSION: Development of a new nanoparticle test may provide a quantitative measure of the prostate cancer aggressiveness. If validated in a larger study of patients with prostate cancer, this test could become a new diagnostic tool in conjunction with Gleason Score pathology diagnostics to better distinguish aggressive cancer from indolent tumor.

Toward an integrated knowledge environment to support modern oncology.

Around the world, teams of researchers continue to develop a wide range of systems to capture, store, and analyze data including treatment, patient outcomes, tumor registries, next-generation sequencing, single-nucleotide polymorphism, copy number, gene expression, drug chemistry, drug safety, and toxicity. Scientists mine, curate, and manually annotate growing mountains of data to produce high-quality databases, while clinical information is aggregated in distant systems. Databases are currently scattered, and relationships between variables coded in disparate datasets are frequently invisible. The challenge is to evolve oncology informatics from a "systems" orientation of standalone platforms and silos into an "integrated knowledge environments" that will connect "knowable" research data with patient clinical information. The aim of this article is to review progress toward an integrated knowledge environment to support modern oncology with a focus on supporting scientific discovery and improving cancer care.

Acute intraprocedural thrombus formation during wingspan intracranial stent placement for intracranial atherosclerotic disease.

BACKGROUND: Treatment of intracranial atherosclerotic disease with the Wingspan-Gateway intracranial stent and balloon angioplasty system has been reported in several multicenter registries. To date, the incidence of acute intraprocedural thrombus formation during Wingspan stent placement has not been reported. OBJECTIVE: We reviewed the incidence of acute thrombus formation, treatment, and outcome for patients who underwent Wingspan stent placement by the senior author (B.L.H.) between June 2006 and April 2009. METHODS: We routinely perform angiograms every 10 minutes for at least 30 minutes after placement of a Wingspan stent to check for acute thrombus formation. Acute thrombus was graded: (1) visible thrombus but not flow limiting, (2) visible and flow-limiting thrombosis, and (3) complete stent occlusion. Recanalization was graded according to Thrombosis In Myocardial Infarction score. RESULTS: Forty-one patients underwent Wingspan stent placement for intracranial stenosis. Acute intraprocedural thrombus formation developed in 6 (14.6%) within 20 minutes after stent placement: 3 grade 1, 1 grade 2, and 2 grade 3. All 6 were successfully recanalized with Thrombosis In Myocardial Infarction score 3 after intravenous abciximab with or without intra-arterial tissue plasminogen activator and/or balloon angioplasty. There was no morbidity, and all 6 patients were discharged home at their neurological baseline. CONCLUSION: We recommend serial angiography every 10 minutes for at least 30 minutes after placement of Wingspan stents. Once detected, acute thrombosis can be successfully treated with intravenous abciximab with or without intra-arterial tissue plasminogen activator and/or balloon angioplasty.

Tamoxifen malabsorption after Roux-en-Y gastric bypass surgery: case series and review of the literature.

Roux-en-Y gastric bypass is a gastric reduction duodenal switch with a combination of restrictive and malabsorptive procedures. It is the most common gastric bypass procedure performed in the United States. Malabsorption causing nutritional deficiencies does occur, yet a PubMed literature search (1955-2009) returned no reports of malabsorption of anticancer agents after gastric bypass. To our knowledge, this is the first report of three cases of malabsorption of the anticancer agent tamoxifen after this procedure. The first patient was a 58-year-old woman who underwent Roux-en-Y bypass for morbid obesity. Two years later, she developed estrogen receptor-positive ductal carcinoma in situ of the breast, underwent lumpectomy and irradiation, and tamoxifen was started. Two years after that, she presented with concerns of potential malabsorption of the drug. Her plasma tamoxifen level was 28 ng/ml, which was below the lower limit of the therapeutic range (77-274 ng/ml for 10-30-mg/day regimens). The second patient was a 51-year-old woman who sought medical advice on risk reduction for breast cancer after receiving a diagnosis of atypical ductal hyperplasia of the breast. She also had a history of morbid obesity and underwent Roux-en-Y bypass. Tamoxifen was started to reduce her risk of breast cancer; her plasma tamoxifen level was subtherapeutic at 14 ng/ml. The third patient was a 53-year-old woman with estrogen receptor-positive breast cancer who underwent lumpectomy and was prescribed anastrozole, an aromatase inhibitor. She also underwent Roux-en-Y bypass for morbid obesity. As she experienced adverse effects while receiving anastrozole, the drug was discontinued, and tamoxifen 20 mg/day was started. Her tamoxifen plasma level was 52 ng/ml. Therefore, her tamoxifen dosage was increased to 20 mg twice/day. Six weeks later, her tamoxifen level was 120 ng/ml (therapeutic range 95-520 ng/ml for the increased dosage). These three cases suggest that steady-state serum tamoxifen levels should be evaluated in patients who have undergone Roux-en-Y gastric bypass. Until adequate data suggest otherwise, parenteral anticancer alternatives should be considered when systemic therapy is needed in a patient with malabsorption.

Radiographic and pathologic findings in an atypical brainstem variant of reversible posterior leukoencephalopathy syndrome.

BACKGROUND: Reversible posterior leukoencephalopathy syndrome (RPLS) and hypertensive encephalopathy (HE) are terms generally used interchangeably to describe a syndrome characterized by encephalopathy, focal deficits, and vasogenic edema seen on magnetic resonance imaging, which are potentially reversible with treatment. The underlying pathologic changes are less well defined. Previously, the only pathologic data available came from a single autopsy series. Results from a recent biopsy report differ with the autopsy series leading to the suggestion that RPLS and HE may be distinct. CASE REPORT: We report a markedly hypertensive patient with encephalopathy and hemiparesis and focal edema in the brainstem visualized on magnetic resonance imaging. A biopsy was performed that demonstrated pathologic changes associated with RPLS. With treatment of hypertension, the patient's symptoms resolved completely. CONCLUSIONS: We report an unusual brainstem variant of RPLS, adding to the neuropathologic features of this syndrome, and supporting the predominant view that RPLS and HE have a shared pathologic basis.

Managing symptoms among patients with breast cancer during chemotherapy: results of a two-arm behavioral trial.

PURPOSE: In this study, we compare symptom response and times to response among patients with breast cancer who were assigned to either a cognitive behavioral Nurse-Administered Symptom Management intervention or an Automated Telephone Symptom Management (ATSM) intervention. PATIENTS AND METHODS: Patients with breast cancer were identified from a larger trial. Baseline equivalence existed between arms, and there was no differential attrition by arm. Anchor-based definition of response using mild, moderate, and severe categories of symptom severity were used. Responses and times to response for 15 symptoms were investigated in relation to trial arm, comorbid conditions, treatment protocols, and metastatic versus localized disease. RESULTS: The ATSM arm was more effective among patents with metastatic disease. Compared with patients receiving combination chemotherapy protocols, those treated with single agents had greater response and shorter time to response. CONCLUSION: An educational information intervention delivered via an automated voice response system that assesses symptoms and refers patients to a Symptom Management Guide is more effective than a complex cognitive behavioral approach in terms of producing greater symptom responses in shorter time intervals among patients with metastatic disease.

Steroid treatment of primary progressive aphasia.

OBJECTIVE: To learn if oral steroid treatment can alter the signs of primary progressive aphasia (PPA). Many patients with PPA have had a vasectomy and there is a possible link between vasectomy and autoimmune diseases. If PPA is, at least in part, an autoimmune disease, patients might improve with immunosuppressant treatment. DESIGN: Case report. SETTING: Cognitive and memory clinic. PATIENT: A 68-year-old right-handed man with a 2.5-year history of progressive speech impairment who had a vasectomy 25 years prior. RESULTS: Examination revealed that he had a nonfluent aphasia with intact repetition and comprehension. Before and during oral prednisone treatment, he was assessed for speech fluency, naming, and episodic and working memory. All assessments except episodic memory showed a dramatic improvement. On reassessment 1 month after discontinuing treatment, the patient's performance on cognitive testing had regressed toward baseline. CONCLUSIONS: Although this patient's improvement with steroid treatment provides support for the postulate that PPA might be a treatable autoimmune disease, future placebo-controlled trials are needed before conclusions can be drawn.

Establishing mild, moderate, and severe scores for cancer-related symptoms: how consistent and clinically meaningful are interference-based severity cut-points?

Methods are presented to separate 16 frequently occurring cancer symptoms measured on 10-point symptom severity rating scales into mild, moderate, and severe categories that are clinically interpretable and significant for use in oncology practice settings. At their initial intervention contact, 588 solid tumor cancer patients undergoing chemotherapy reported severity on a standard 11-point rating scale for 16 symptoms. All reporting a one or higher were asked to rate on an 11-point scale how much the symptom interfered with enjoyment of life, relationship with others, general daily activities, and emotions. Factor analysis revealed that these items tapped into the same dimension, and the items were summed to form an interference scale. Cut-points for mild, moderate, and severe categories of symptom severity were defined by comparing the differences in interference scores corresponding to each successive increases in severity for each symptom. The cut-points differed among symptoms. Pain, fatigue, weakness, cough, difficulty remembering, and depression had lower cut-points for each category compared to other symptoms. Cut-points for each symptom were not related to site or stage of cancer, age, or gender but were associated with a global depression measure. Cut-points were related to limitations in physical function, suggesting differences in the quality of patients' lives. The resulting cut-points summarize severity ratings into clinically significant and useful categories that clinicians can use to assess symptoms in their practices.

Molecular classification system identifies invasive breast carcinoma patients who are most likely and those who are least likely to achieve a complete pathologic response after neoadjuvant chemotherapy.

BACKGROUND: The molecular classification system categorizes invasive breast carcinomas according to their key driving biomarkers. In the current study, the authors evaluated whether response to neoadjuvant chemotherapy was correlated with the molecular classification groups. METHODS: Using immunohistochemistry, the molecular classification group (luminal-A, luminal-B, HER-2-variant, HER-2-classic, and basal phenotype) was retrospectively determined in 68 breast cancer patients who received neoadjuvant treatment. RESULTS: A total of 28 carcinoma patients (41.2%) achieved a compete pathologic response (CPR), including 2 of 15 patients classified as having luminal-A (13.3%), 4 of 16 patients classified as having luminal-B (25.0%), 10 of 12 patients classified as having HER-2-classic (83.3%), none of the 4 patients classified as having HER-2-variant, and 12 of 21 patients classified as having basal phenotype (57.1%) neoplasms. The CPR rate among patients with the HER-2-classic and basal neoplasms was 67% (22 of 33 neoplasms), compared with 17.1% (6 of 35 neoplasms) in the non-HER-2-classic/basal combined group (P < .001). Eleven carcinomas were initially diagnosed as invasive lobular carcinomas (pleomorphic and classic), 4 of which were luminal-A, 4 of which were luminal-B, 2 of which were HER-2-classic, and 1 of which was basal. On review, only 3 of these 11 cases remained classified as classic lobular carcinoma, all of which were classified as luminal-A, and none of these patients achieved a CPR. Four of the other 8 patients achieved a CPR. CONCLUSIONS: The molecular classification system is useful for identifying carcinoma patients who are most likely and those who are least likely to achieve a CPR. In the current study, all the morphologically classic lobular carcinomas were classified as luminal-A neoplasms, which may explain the low rate of CPR reported.