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Australia’s fisheries have experience in responding individually to specific shocks to stock levels (for example, marine heatwaves, floods) and markets (for example, global financial crisis, food safety access barriers). The COVID-19 pandemic was, however, novel in triggering a series of systemic shocks and disruptions to the activities and operating conditions for all Australia’s commercial fisheries sectors including those of the research agencies that provide the information needed for their sustainable management. While these disruptions have a single root cause—the public health impacts and containment responses to the COVID-19 pandemic—their transmission and effects have been varied. We examine both the impacts on Australian fisheries triggered by measures introduced by governments both internationally and domestically in response to the COVID-19 pandemic outbreak, and the countermeasures introduced to support continuity in fisheries and aquaculture production and supply chains. Impacts on fisheries production are identified by comparing annual and monthly catch data for Australia’s commercial fisheries in 2020 with averages for the last 4–5 years. We combine this with a survey of the short-term disruption to and impacts on research organisations engaged in fisheries monitoring and assessment and the adaptive measures they deployed. The dominant impact identified was triggered by containment measures both within Australia and in export receiving countries which led to loss of export markets and domestic dine-in markets for live or fresh seafood. The most heavily impact fisheries included lobster and abalone (exported live) and specific finfishes (exported fresh or sold live domestically), which experienced short-term reductions in both production and price. At the same time, improved prices and demand for seafood sold into domestic retail channels were observed. The impacts observed were both a function of the disruptions due to the COVID-19 pandemic and the countermeasures and support programs introduced by various national and state-level governments across Australia to at least partly mitigate negative impacts on harvesting activities and supply chains. These included protecting fisheries activities from specific restrictive COVID-19 containment measures, pro-actively re-establishing freight links, supporting quota roll-overs, and introducing wage and businesses support packages. Fisheries research organisations were impacted to various degrees, largely determined by the extent to which their field monitoring activities were protected from specific restrictive COVID-19 containment measures by their state-level governments. Responses of these organisations included reducing fisheries dependent and independent data collection as required while developing strategies to continue to provide assessment services, including opportunistic innovations to harvest data from new data sources. Observed short run impacts of the COVID-19 pandemic outbreak has emphasised both the vulnerability of fisheries dependent on export markets, live or fresh markets, and long supply chains and the resilience of fisheries research programs. We suggest that further and more comprehensive analysis over a longer time period of the long-run impacts of subsequent waves of variants, extended pandemic containment measures, autonomous and planned adaptive responses would be beneficial for the development of more effective counter measures for when the next major external shock affects Australian fisheries.

To aid in the diagnosis and treatment of patients with metastatic tumor seeding, an exceedingly rare phenomenon following minimally invasive urological surgery, additional case reports are needed.We report our experience with patients determined to have peritoneal carcinomatosis following robotic-assisted radical prostatectomy (RARP) and provide a descriptive summary of these unique cases.Five cases of peritoneal carcinomatosis were identified, all of which occurred relatively late-between 8 and 13 years-following RARP. Four of the 5 cases had T3 disease at the time of prostatectomy.Certain clinical factors, such as advanced pathologic stage at the time of prostatectomy, may predict risk for carcinomatosis following RARP. Additionally, next-generation imaging modalities, such as PSMA PET, may aid in identifying these metastases and are likely to identify increasing numbers of these patients as next-generation imaging becomes more widely available. Continued documentation and classification of this atypical presentation are needed to improve our understanding and management of this phenomenon.

Supplementary Figure S1. Talazoparib inhibition of PBMC PARP activity.

Supplementary Figure S1: Evaluation of pre-amplication. Supplementary Figure S2: Algorithm for CTC positivity. Supplementary Figure S3: CTC isolation and gene analysis methodology. Supplementary Figure S4: Validation of gene expression. Supplementary Figure S5: CTC status is not predictive of overall survival. Supplementary Figure S6: miCTC score flowsheet. Supplementary Table 1: primer tables. Supplementary Table 2: Ct values.

Supplementary Methods includes additional details on these topics: tumors eligible for dose escalation phase; tumors eligible for dose expansion phase; patients enrolled using a local laboratory; study design and participants; additional inclusion criteria; full list of exclusion criteria; study treatment; study procedures; pharmacodynamic (PD) analysis; inhibition of PBMC PARP activity.

Supplementary Table S1. Dose-response and exposure-response parameters.

Falchook et al: Development of 2 Bromodomain and Extraterminal Inhibitors With Distinct Pharmacokinetic and Pharmacodynamic Profiles for the Treatment of Advanced Malignancies - Supplemental Methods, Results, Tables, and Figures

Supplementary Table 1 from Characterization of Bone Metastases from Rapid Autopsies of Prostate Cancer Patients

Supplementary Figure 2 from Characterization of Bone Metastases from Rapid Autopsies of Prostate Cancer Patients

Supplementary Table 2 from Characterization of Bone Metastases from Rapid Autopsies of Prostate Cancer Patients

Supplemental Figures 1-4. Supplemental Figure 1: Group Mean Concentration-Time Profiles and the Linear 2 Compartment Model Fit For Weekly Dosing Cohorts Supplemental Figure 2: Effect of Demcizumab on Hair Follicle Biomarkers Supplemental Figure 3: Effect of Demcizumab on Plasma Proteins Supplemental Figure 4: Duration on Study by Patient

Supplementary Figure and Table Legends from Characterization of Bone Metastases from Rapid Autopsies of Prostate Cancer Patients

Purpose: This phase I trial evaluated the safety, pharmacokinetics, and pharmacodynamics of demcizumab (OMP-21M18), a humanized IgG2 mAb targeting the Notch ligand DLL4 in adult patients with advanced malignancies.Experimental Design: Standard 3+3 design, with demcizumab 0.5, 1, 2.5, or 5 mg/kg weekly or 2.5, 5, or 10 mg/kg every other week, with an expansion cohort at 10 mg/kg every other week. Dose-limiting toxicities (DLT) were assessed during the first 28 days.Results: Fifty-five patients received demcizumab (15 weekly, 18 every other week, 21 expansion cohort, 1 loading dose). No more than one DLT was seen at any dose level. The MTD was not reached for either schedule. Treatment-related adverse events occurring in >10% of patients were hypertension or blood pressure increased (47%), fatigue (31%), anemia (22%), headache (20%), nausea (13%), hypoalbuminemia (11%), dizziness (11%), and dyspnea (11%). One patient dosed at 2.5 mg/kg developed reversible right-sided heart failure after 63 days on treatment and 4 dosed at 10 mg/kg developed congestive heart failure after ≥98 days on treatment. Five patients were hospitalized with bleeding episodes (2 episodes of tumor-associated bleeding). Sixteen of 25 (64%) evaluable patients at 10 mg/kg had evidence of stabilization of disease or response.Conclusion: Demcizumab was generally well tolerated at doses ≤5 mg weekly with disease stabilization and decreases in tumor size demonstrating antitumor activity. Hypertension was the most common adverse event that was clearly related to treatment. Prolonged administration was associated with an increased risk of congestive heart failure. Clin Cancer Res; 20(24); 6295–303. ©2014 AACR.

Supplemental Tables 1-4. Supplemental Table 1: Treatment Emergent Adverse Events By Cohort (All Grades) Reported by >15% of Patients Supplemental Table 2: Pharmacokinetic NCA Parameters by Cohort Supplemental Table 3: Compartmental PK Analysis Final Parameter Estimates and Estimation Statistics Supplemental Table 4: RECIST Best Overall Tumor Response

Purpose:Bromodomain and extraterminal (BET) proteins are key epigenetic transcriptional regulators, inhibition of which may suppress oncogene expression. We report results from 2 independent first-in-human phase 1/2 dose–escalation and expansion, safety and tolerability studies of BET inhibitors INCB054329 (study INCB 54329-101; NCT02431260) and INCB057643 (study INCB 57643-101; NCT02711137).Patients and Methods:Patients (≥18 years) with advanced malignancies, ≥1 prior therapy, and adequate organ functions received oral INCB054329 (monotherapy) or INCB057643 (monotherapy or in combination with standard-of-care) in 21-day cycles (or 28-day cycles depending on standard-of-care combination). Primary endpoints were safety and tolerability.Results:Sixty-nine and 134 patients received INCB054329 and INCB057643, respectively. Study INCB 54329-101 has been completed; INCB 57643-101 is currently active, but not recruiting (no patients were receiving treatment as of January 8, 2019). Terminal elimination half-life was shorter for INCB054329 versus INCB057643 (mean [SD], 2.24 [2.03] vs. 11.1 [8.27] hours). INCB054329 demonstrated higher interpatient variability in oral clearance versus INCB057643 (CV%, 142% vs. 45.5%). Most common (>20%) any-grade treatment-related adverse events were similar for both drugs (INCB054329; INCB057643): nausea (35%; 30%), thrombocytopenia (33%; 32%), fatigue (29%; 30%), decreased appetite (26%; 22%). Two confirmed complete responses and 4 confirmed partial responses with INCB057643 were reported as best responses.Conclusions:INCB057643 exhibited a more favorable PK profile versus INCB054329; exposure-dependent thrombocytopenia was observed with both drugs which limited the target inhibition that could be safely maintained. Further efforts are required to identify patient populations that can benefit most, and an optimal dosing scheme to maximize therapeutic index.

Supplementary Figure 1 from Characterization of Bone Metastases from Rapid Autopsies of Prostate Cancer Patients

Purpose: Bone is the most common metastatic site for prostate cancer, and osseous metastases are the leading cause of morbidity from this disease. Recent autopsy studies prove that 100% of men who die of prostate cancer have bone involvement. Understanding the biology of prostate cancer and its evolution to an incurable androgen-independent phenotype requires an understanding of the genetic and cellular alterations that lead to the seeding and proliferation of tumor foci in bone, as well as the microenvironment in which these metastases arise. No intensive studies, however, have been conducted on osseous metastatic tissues from patients with metastatic prostate cancer due to lack of access to such tissues for profiling and other research.Experimental Design: We show, for the first time, a reproducible methodology to obtain high quality clinical tumor tissues metastatic to the bone. This technique allowed the procurement of viable metastatic tumor tissue from involved bones in 13 recent autopsies conducted at the University of Michigan and analyzed the gene expression of these tissues using real-time PCR and microarrays.Results: We present here the discovery of nonossified bone metastases from multiple patients with advanced prostate cancer and their subsequent characterization and comparison to nonosseous metastases from the same patients.Conclusion: This represents a versatile and practical approach that may be employed to characterize the steps in metastasis and the phenotypic characteristics of osseous metastasis of prostate cancer and to profile RNA, DNA, and cDNA from tumor samples metastatic to the bone. Clin Cancer Res; 17(12); 3924–32. ©2011 AACR.

INTRODUCTION: Fibroblast growth factor receptor (FGFR)-4/FGF19 pathway dysregulation is implicated in hepatobiliary and other solid tumors. INCB062079, an oral, selective, FGFR4 inhibitor, inhibits growth in FGF19/FGFR4-driven liver cancer models. METHODS: This was a two-part, phase I study (NCT03144661) in previously treated patients with advanced solid tumors. The primary objective was to determine safety, tolerability, and maximum tolerated dose (MTD), while secondary objectives included pharmacokinetics, pharmacodynamics (plasma FGF19; bile acid salts/7α-hydroxy-4-cholesten-3-one [C4] levels), and preliminary efficacy. In Part 1, patients received INCB062079 starting at 10 mg once daily, with 3 + 3 dose escalation. Part 2 (dose expansion) was not conducted because of study termination. RESULTS: Twenty-three patients were treated (hepatobiliary, n = 11; ovarian, n = 9; other, n = 3). Among six patients receiving 15 mg twice daily, two patients had dose-limiting toxicities (DLTs; grade 3 diarrhea, grade 3 transaminitis). Both had high pretreatment C4 concentrations, prompting a protocol amendment requiring pretreatment C4 concentrations

Purpose The combination of paclitaxel, ifosfamide, and cisplatin (TIP) is frequently used for the treatment of metastatic germ cell tumors. Due to complex supportive care and infusion requirements, TIP is typically given in the inpatient setting. This analysis describes the development and implementation of a protocol for complete outpatient administration of TIP chemotherapy. Methods From July 2020 to June 2021, adults receiving TIP for germ cell tumor at University of Michigan Rogel Cancer Center were evaluated for outpatient administration. The primary outcome was number of inpatient bed days saved by giving outpatient TIP chemotherapy, with the goal of giving 75% of TIP cycles outpatient. Patients receiving outpatient TIP were also assessed for chemotherapy dose reduction or delays and acute toxicities of kidney injury, encephalopathy, and hemorrhagic cystitis. Results From July 2020 to July 2021, three patients received 13 cycles of TIP. Ten cycles (77%) were administered in the outpatient setting, resulting in a savings of 50 inpatient bed days in one year. No patients required a dose reduction or delay in chemotherapy or experienced acute kidney injury, encephalopathy, or hemorrhagic cystitis during outpatient TIP treatment. Conclusion Despite logistic and supportive care challenges, TIP can be administered completely in the outpatient setting.

OBJECTIVE To evaluate the Brucella suis exposure status of pigs raised with outdoor access on farms in New York State and assess biosecurity and management practices of those farms. ANIMALS 250 pigs that were raised for commercial purposes, had access to the outdoors, and were > 4 months of age on 24 farms in New York State. PROCEDURES Farms were randomly selected from a sampling frame generated for the study and contacted to recruit them to participate. Participating farms were provided a questionnaire to complete. Up to 30 pigs per farm were tested for serum anti-Brucella antibodies. RESULTS Farm were classified as seasonal and year round. Seasonal farms raised pigs for slaughter, and year-round farms bred pigs, raised them for slaughter, and sold live pigs to others to raise. None of the 250 pigs had antibodies to Brucella spp. Nevertheless, the biosecurity assessment revealed a need for enhanced practices in procurement and management of swine in a wide range of areas. CLINICAL RELEVANCE There was no evidence for ongoing B suis infection on these swine farms in New York State, but biosecurity and preventive practices at these facilities could be improved to prevent the introduction and spread of B suis and other pathogens.

The combination of lithographic methods and sol gel bottom-up techniques is a promising approach for nanopatterning substrates. The integration and scalable fabrication of such substrates are of great interest for the development of nanowire-based materials opening potentialities in new technologies. We demonstrate the deposition of ordered mesoporous silica into nanopatterned silica substrates by dip coating. Using scanning electron microscopy and grazing incidence small angle X-ray scattering, the effect of the sol composition on the pore ordering was probed. Optimising the sol composition using anodic alumina membranes as confined spaces, we showed how the pH controlled the transformation from circular to columnar mesophase. Vertical mesopores were obtained with very good repeatability. The effect of the sol chemistry on the surfactant curvature was then shown to be similar in nanopatterned substrates made by e-beam lithography.

The substantial biological heterogeneity of metastatic prostate cancer has hindered the development of personalized therapeutic approaches. Therefore, it is difficult to predict the course of metastatic hormone-sensitive prostate cancer (mHSPC), with some men remaining on first-line androgen deprivation therapy (ADT) for several years while others progress more rapidly. Improving our ability to risk-stratify patients would allow for the optimization of systemic therapies and support the development of stratified prospective clinical trials focused on patients likely to have the greatest potential benefit. Here, we applied a liquid biopsy approach to identify clinically relevant, blood-based prognostic biomarkers in patients with mHSPC. Gene expression indicating the presence of CTCs was greater in CHAARTED high-volume (HV) patients (52% CTChigh) than in low-volume (LV) patients (23% CTChigh; * p = 0.03). HV disease (p = 0.005, q = 0.033) and CTC presence at baseline prior to treatment initiation (p = 0.008, q = 0.033) were found to be independently associated with the risk of nonresponse at 7 months. The pooled gene expression from CTCs of pre-ADT samples found AR, DSG2, KLK3, MDK, and PCA3 as genes predictive of nonresponse. These observations support the utility of liquid biomarker approaches to identify patients with poor initial response. This approach could facilitate more precise treatment intensification in the highest risk patients.