Open-label, phase II, multicenter study of lasofoxifene plus abemaciclib for treating women with metastatic ER+/HER2- breast cancer and an ESR1 mutation after disease progression on prior therapies: ELAINE 2.

BACKGROUND: Acquired ESR1 mutations in estrogen receptor-positive (ER+) metastatic breast cancer (mBC) drive treatment resistance and tumor progression; new treatment strategies are needed. Lasofoxifene, a next-generation, oral, endocrine therapy and tissue-specific ER antagonist, provided preclinical antitumor activity, alone or combined with a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) in ESR1-mutated mBC. PATIENTS AND METHODS: In the open-label, phase II, ELAINE 2 trial (NCT04432454), women with ESR1-mutated, ER+/human epidermal growth factor receptor 2-negative (HER2-) mBC who progressed on prior therapies (including CDK4/6i) received lasofoxifene 5 mg/day and abemaciclib 150 mg b.i.d until disease progression/toxicity. The primary endpoint was safety/tolerability. Secondary endpoints included progression-free survival (PFS), clinical benefit rate (CBR), and objective response rate (ORR). RESULTS: Twenty-nine women (median age 60 years) participated; all but one were previously treated with a CDK4/6i (median duration 2 years). The lasofoxifene-abemaciclib combination was well tolerated with primarily grade 1/2 treatment-emergent adverse events (TEAEs), most commonly diarrhea, nausea, fatigue, and vomiting. One patient (with no prior CDK4/6i) discontinued treatment due to grade 2 diarrhea. No deaths occurred during the study. Median PFS was 56.0 weeks [95% confidence interval (CI) 31.9 weeks-not estimable; ∼13 months]; PFS rates at 6, 12, and 18 months were 76.1%, 56.1%, and 38.8%, respectively. CBR at 24 weeks was 65.5% (95% CI 47.3% to 80.1%). In 18 patients with measurable lesions, ORR was 55.6% (95% CI 33.7% to 75.4%). ESR1-mutant circulating tumor DNA (ctDNA) allele fraction decreased from baseline to week 4 in 21/26 (80.8%) patients. CONCLUSIONS: Lasofoxifene plus abemaciclib had an acceptable safety profile, was well tolerated, and exhibited meaningful antitumor activity in women with ESR1-mutated, ER+/HER2- mBC after disease progression on prior CDK4/6i. Observed decreases in ESR1-mutant ctDNA with lasofoxifene concordant with clinical response suggest target engagement. If the ELAINE 2 findings are confirmed in the initiated, phase III, ELAINE 3 trial, these data could be practice-changing and help address a critical unmet need.

Delay in Source Control in Perforated Peptic Ulcer Leads to 6% Increased Risk of Death Per Hour: A Nationwide Cohort Study.

BACKGROUND: Delay to theatre for patients with intra-abdominal sepsis is cited as a particular risk factor for death. Our aim was to evaluate the potential relationship between hourly delay from admission to surgery and post-operative mortality in patients with perforated peptic ulcer (PPU). METHODS: All patients entered in the National Emergency Laparotomy Audit who had an emergency laparotomy for PPU within 24 h of admission from December 2013 to November 2017 were included. Time to theatre from admission was modelled as a continuous variable in hours. Outcome was 90-day mortality. Logistic regression adjusting for confounding factors was performed. RESULTS: 3809 patients were included, and 90-day mortality rate was 10.61%. Median time to theatre was 7.5 h (IQR 5-11.6 h). The odds of death increased with time to operation once adjustment for confounding variables was performed (per hour after admission adjusted OR 1.04 95% CI 1.02-1.07). In patients who were physiologically shocked (N = 334), there was an increase of 6% in risk-adjusted odds of mortality for every hour Em Lap was delayed after admission (OR 1.06 95% CI 1.01-1.11). CONCLUSION: Hourly delay to theatre in patients with PPU is independently associated with risk of death by 90 days. Therefore, we suggest that surgical source control should occur as soon as possible after admission regardless of time of day.

Modelling of the electrocardiographic signal during an angioplasty procedure in the right coronary artery.

Dynamical models are useful tools to generate sets of varied morphological signals by synthesizing human electrocardiograms (ECGs). These signals are used for testing and improving algorithms of ECG delineation, patient monitoring and heart disease detection. This work presents a procedure based on the ECGSYN model to synthesize ECG morphological changes induced by a percutaneous transluminal coronary angioplasty (PTCA) procedure in the right coronary artery. We provide a set of parameters to be used in ECGSYN and generate heartbeats with altered ST-T complexes. These characteristic model parameters were obtained through a non-linear fitting algorithm applied to every available heartbeat. To extend these parameters, normal distributions were generated with their means and standard deviations obtained from the STAFF III database. Parameters were presented for P, QRS and T-waves at leads II, III and aVF. The synthesis procedure shows an average correlation and positive predictive value of 92.2% and 88.2%, respectively. In conclusion, we provide a technique capable of synthesizing electrocardiographic ischemic morphology with physiological plausibility. Then, the generation of data sets for algorithm testing can benefit from this system of ECG signal synthesis.

Association between surgeon special interest and mortality after emergency laparotomy.

BACKGROUND: Approximately 30 000 emergency laparotomies are performed each year in England and Wales. Patients with pathology of the gastrointestinal tract requiring emergency laparotomy are managed by general surgeons with an elective special interest focused on either the upper or lower gastrointestinal tract. This study investigated the impact of special interest on mortality after emergency laparotomy. METHODS: Adult patients having emergency laparotomy with either colorectal or gastroduodenal pathology were identified from the National Emergency Laparotomy Audit database and grouped according to operative procedure. Outcomes included all-cause 30-day mortality, length of hospital stay and return to theatre. Logistic and Poisson regression were used to analyse the association between consultant special interest and the three outcomes. RESULTS: A total of 33 819 patients (28 546 colorectal, 5273 upper gastrointestinal (UGI)) were included. Patients who had colorectal procedures performed by a consultant without a special interest in colorectal surgery had an increased adjusted 30-day mortality risk (odds ratio (OR) 1·23, 95 per cent c.i. 1·13 to 1·33). Return to theatre also increased in this group (OR 1·13, 1·05 to 1·20). UGI procedures performed by non-UGI special interest surgeons carried an increased adjusted risk of 30-day mortality (OR 1·24, 1·02 to 1·53). The risk of return to theatre was not increased (OR 0·89, 0·70 to 1·12). CONCLUSION: Emergency laparotomy performed by a surgeon whose special interest is not in the area of the pathology carries an increased risk of death at 30 days. This finding potentially has significant implications for emergency service configuration, training and workforce provision, and should stimulate discussion among all stakeholders.

Thirty-day mortality in patients undergoing laparotomy for small bowel obstruction.

BACKGROUND: Small bowel obstruction (SBO) is a common indication for emergency laparotomy. There are currently variations in the timing of surgery for patients with SBO and limited evidence on whether delayed surgery affects outcomes. The aim of this study was to evaluate the impact of time to operation on 30-day mortality in patients requiring emergency laparotomy for SBO. METHODS: Data were collected from the National Emergency Laparotomy Audit (NELA) on all patients aged 18 years or older who underwent emergency laparotomy for all forms of SBO between December 2013 and November 2015. The primary outcome measure was 30-day mortality, with date of death obtained from the Office for National Statistics. Patients were grouped according to the time from admission to surgery (less than 24 h, 24-72 h and more than 72 h). A multilevel logistic regression model was used to explore the impact of patient factors, primarily delay to surgery, on 30-day mortality. RESULTS: Some 9991 patients underwent emergency laparotomy requiring adhesiolysis or small bowel resection for SBO. The overall mortality rate was 7·2 per cent (722 patients). Within each time group, 30-day mortality rates were significantly worse with increasing age, ASA grade, Portsmouth POSSUM score and level of contamination. Patients undergoing emergency laparotomy more than 72 h after admission had a significantly higher risk-adjusted 30-day mortality rate (odds ratio 1·39, 95 per cent c.i. 1·09 to 1·76). CONCLUSION: In patients who require an emergency laparotomy with adhesiolysis or resection for SBO, a delay to surgery of more than 72 h is associated with a higher 30-day postoperative mortality rate.

Organisational factors and mortality after an emergency laparotomy: multilevel analysis of 39 903 National Emergency Laparotomy Audit patients.

BACKGROUND: Studies across healthcare systems have demonstrated between-hospital variation in survival after an emergency laparotomy. We postulate that this variation can be explained by differences in perioperative process delivery, underpinning organisational structures, and associated hospital characteristics. METHODS: We performed this nationwide, registry-based, prospective cohort study using data from the National Emergency Laparotomy Audit organisational and patient audit data sets. Outcome measures were all-cause 30- and 90-day postoperative mortality. We estimated adjusted odds ratios (ORs) for perioperative processes and organisational structures and characteristics by fitting multilevel logistic regression models. RESULTS: The cohort comprised 39 903 patients undergoing surgery at 185 hospitals. Controlling for case mix and clustering, a substantial proportion of between-hospital mortality variation was explained by differences in processes, infrastructure, and hospital characteristics. Perioperative care pathways [OR: 0.86; 95% confidence interval (CI): 0.76-0.96; and OR: 0.89; 95% CI: 0.81-0.99] and emergency surgical units (OR: 0.89; 95% CI: 0.80-0.99; and OR: 0.89; 95% CI: 0.81-0.98) were associated with reduced 30- and 90-day mortality, respectively. In contrast, infrequent consultant-delivered intraoperative care was associated with increased 30- and 90-day mortality (OR: 1.61; 95% CI: 1.01-2.56; and OR: 1.61; 95% CI: 1.08-2.39, respectively). Postoperative geriatric medicine review was associated with substantially lower mortality in older (≥70 yr) patients (OR: 0.35; 95% CI: 0.29-0.42; and OR: 0.64; 95% CI: 0.55-0.73, respectively). CONCLUSIONS: This multicentre study identified low-technology, readily implementable structures and processes that are associated with improved survival after an emergency laparotomy. Key components of pathways, perioperative medicine input, and specialist units require further investigation.

Development and internal validation of a novel risk adjustment model for adult patients undergoing emergency laparotomy surgery: the National Emergency Laparotomy Audit risk model.

BACKGROUND: Among patients undergoing emergency laparotomy, 30-day postoperative mortality is around 10-15%. The risk of death among these patients, however, varies greatly because of their clinical characteristics. We developed a risk prediction model for 30-day postoperative mortality to enable better comparison of outcomes between hospitals. METHODS: We analysed data from the National Emergency Laparotomy Audit (NELA) on patients having an emergency laparotomy between December 2013 and November 2015. A prediction model was developed using multivariable logistic regression, with potential risk factors identified from existing prediction models, national guidelines, and clinical experts. Continuous risk factors were transformed if necessary to reflect their non-linear relationship with 30-day mortality. The performance of the model was assessed in terms of its calibration and discrimination. Interval validation was conducted using bootstrap resampling. RESULTS: There were 4458 (11.5%) deaths within 30-days among the 38 830 patients undergoing emergency laparotomy. Variables associated with death included (among others): age, blood pressure, heart rate, physiological variables, malignancy, and ASA physical status classification. The predicted risk of death among patients ranged from 1% to 50%. The model demonstrated excellent calibration and discrimination, with a C-statistic of 0.863 (95% confidence interval, 0.858-0.867). The model retained its high discrimination during internal validation, with a bootstrap derived C-statistic of 0.861. CONCLUSIONS: The NELA risk prediction model for emergency laparotomies discriminates well between low- and high-risk patients and is suitable for producing risk-adjusted provider mortality statistics.

Current management of small bowel obstruction in the UK: results from the National Audit of Small Bowel Obstruction clinical practice survey.

AIM: Small bowel obstruction (SBO) is associated with high rates of morbidity and mortality. The National Audit of Small Bowel Obstruction (NASBO) is a collaboration between trainees and specialty associations to improve the care of patients with SBO through national clinical audit. The aim of this study was to define current consultant practice preferences in the management of SBO in the UK. METHOD: A survey was designed to assess practice preferences of consultant surgeons. The anonymous survey captured demographics, indications for surgery or conservative management, use of investigations including water-soluble contrast agents (WSCA), use of laparoscopy and nutritional support strategies. The questionnaire underwent two pilot rounds prior to dissemination via the NASBO network. RESULTS: A total of 384 responses were received from 131 NASBO participating units (overall response rate 29.2%). Abdominal CT and serum urea and electrolytes were considered essential initial investigations by more than 80% of consultants. Consensus was demonstrated on indications for early surgery and conservative management. Three hundred and thirty-eight (88%) respondents would consider use of WSCA; of these, 328 (97.1%) would use it in adhesive SBO. Two hundred (52.1%) consultants considered a laparoscopic approach when operating for SBO. Oral nutritional supplements were favoured in operatively managed patients by 259 (67.4%) respondents compared with conservatively managed patients (186 respondents, 48.4%). CONCLUSION: This survey demonstrates consensus on imaging requirements and indications for early surgery in the management of SBO. Significant variation exists around awareness of the need for nutritional support in patients with SBO, and on strategies to achieve this support.

Detection of infectious spleen and kidney necrosis virus (ISKNV) and turbot reddish body iridovirus (TRBIV) from archival ornamental fish samples.

Although infections caused by megalocytiviruses have been reported from a wide range of finfish species for several decades, molecular characterisation of the viruses involved has been undertaken only on more recent cases. Sequence analysis of the major capsid protein and adenosine triphosphatase genes is reported here from formalin-fixed, paraffin-embedded material from 2 archival ornamental fish cases from 1986 and 1988 in conjunction with data for a range of genes from fresh frozen tissues from 5 cases obtained from 1991 through to 2010. Turbot reddish body iridovirus (TRBIV) genotype megalocytiviruses, previously not documented in ornamental fish, were detected in samples from 1986, 1988 and 1991. In contrast, megalocytiviruses from 1996 onwards, including those characterised from 2002, 2006 and 2010 in this study, were almost indistinguishable from infectious spleen and kidney necrosis virus (ISKNV). Three of the species infected with TRBIV-like megalocytiviruses from 1986 to 1991, viz. dwarf gourami Trichogaster lalius (formerly Colisa lalia), freshwater angelfish Pterophyllum scalare and oscar Astronotus ocellatus, were infected with ISKNV genotype megalocytiviruses from 2002 to 2010. The detection of a TRBIV genotype isolate in ornamental fish from 1986 represents the index case, confirmed by molecular sequence data, for the genus Megalocytivirus.

Preclinical characterisation of the GM-CSF receptor as a therapeutic target in rheumatoid arthritis.

OBJECTIVE: Previous work has suggested that the granulocyte macrophage colony stimulating factor (GM-CSF)-GM-CSF receptor α axis (GM-CSFRα) may provide a new therapeutic target for the treatment of rheumatoid arthritis (RA). Therefore, we investigated the cellular expression of GM-CSFRα in RA synovial tissue and investigated the effects of anti-GM-CSFRα antibody treatment in vitro and in vivo in a preclinical model of RA. METHODS: We compared GM-CSFRα expression on macrophages positive for CD68 or CD163 on synovial biopsy samples from patients with RA or psoriatic arthritis (PsA) to disease controls. In addition, we studied the effects of CAM-3003, an anti-GM-CSFR antibody in a collagen induced arthritis model of RA in DBA/1 mice. The pharmacokinetic profile of CAM-3003 was studied in naïve CD1(ICR) mice (see online supplement) and used to interpret the results of the pharmacodynamic studies in BALB/c mice. RESULTS: GM-CSFRα was expressed by CD68 positive and CD163 positive macrophages in the synovium, and there was a significant increase in GM-CSFRα positive cells in patients in patients with RA as well as patients with PsA compared with patients with osteoarthritis and healthy controls. In the collagen induced arthritis model there was a dose dependent reduction of clinical arthritis scores and the number of F4/80 positive macrophages in the inflamed synovium after CAM-3003 treatment. In BALB/c mice CAM-3003 inhibited recombinant GM-CSF mediated margination of peripheral blood monocytes and neutrophils. CONCLUSIONS: The findings support the ongoing development of therapies aimed at interfering with GM-CSF or its receptor in various forms of arthritis, such as RA and PsA.

Social-economical decision making in current and remitted major depression.

BACKGROUND: Prosocial emotions related to self-blame are important in guiding human altruistic decisions. These emotions are elevated in major depressive disorder (MDD), such that MDD has been associated with guilt-driven pathological hyper-altruism. However, the impact of such emotional impairments in MDD on different types of social decision-making is unknown. METHOD: In order to address this issue, we investigated different kinds of altruistic behaviour (interpersonal cooperation and fund allocation, altruistic punishment and charitable donation) in 33 healthy subjects, 35 patients in full remission (unmedicated) and 24 currently depressed patients (11 on medication) using behavioural-economical paradigms. RESULTS: We show a significant main effect of clinical status on altruistic decisions (p = 0.04) and a significant interaction between clinical status and type of altruistic decisions (p = 0.03). More specifically, symptomatic patients defected significantly more in the Prisoner's Dilemma game (p < 0.05) and made significantly lower charitable donations, whether or not these incurred a personal cost (p < 0.05 and p < 0.01, respectively). Currently depressed patients also reported significantly higher guilt elicited by receiving unfair financial offers in the Ultimatum Game (p < 0.05). CONCLUSIONS: Currently depressed individuals were less altruistic in both a charitable donation and an interpersonal cooperation task. Taken together, our results challenge the guilt-driven pathological hyper-altruism hypothesis in depression. There were also differences in both current and remitted patients in the relationship between altruistic behaviour and pathological self-blaming, suggesting an important role for these emotions in moral and social decision-making abnormalities in depression.

Temporal discounting in major depressive disorder.

BACKGROUND: Major depressive disorder (MDD) is associated with abnormalities in financial reward processing. Previous research suggests that patients with MDD show reduced sensitivity to frequency of financial rewards. However, there is a lack of conclusive evidence from studies investigating the evaluation of financial rewards over time, an important aspect of reward processing that influences the way people plan long-term investments. Beck's cognitive model posits that patients with MDD hold a negative view of the future that may influence the amount of resources patients are willing to invest into their future selves. METHOD: We administered a delay discounting task to 82 participants: 29 healthy controls, 29 unmedicated participants with fully remitted MDD (rMDD) and 24 participants with current MDD (11 on medication). RESULTS: Patients with current MDD, relative to remitted patients and healthy subjects, discounted large-sized future rewards at a significantly higher rate and were insensitive to changes in reward size from medium to large. There was a main effect of clinical group on discounting rates for large-sized rewards, and discounting rates for large-sized rewards correlated with severity of depressive symptoms, particularly hopelessness. CONCLUSIONS: Higher discounting of delayed rewards in MDD seems to be state dependent and may be a reflection of depressive symptoms, specifically hopelessness. Discounting distant rewards at a higher rate means that patients are more likely to choose immediate financial options. Such impairments related to long-term investment planning may be important for understanding value-based decision making in MDD, and contribute to ongoing functional impairment.

State-dependent changes in hippocampal grey matter in depression.

Reduced hippocampal volume has been reported in depression and may be involved in the aetiology of depressive symptoms and vulnerability to depressive relapse. Neuroplasticity following antidepressant drug treatment in the hippocampus has been demonstrated in animal models but adaptive changes after such treatment have not been shown in humans. In this study, we determined whether grey matter loss in the hippocampus in depression (1) is present in medication-free depressed (2) changes in response to antidepressant treatment and (3) is present as a stable trait in medication-free remitted patients. Sixty-four medication-free unipolar depressed patients: 39 currently depressed and 25 in remission, and 66 healthy controls (HC) underwent structural magnetic resonance imaging in a cross-sectional and longitudinal design. Thirty-two currently depressed participants were then treated with the antidepressant citalopram for 8 weeks. Adherence to treatment was evaluated by measuring plasma citalopram concentration. We measured regional variation in grey matter concentration by using voxel-based morphometry-Diffeomorphic Anatomical Registration Through Exponentiated Lie algebra. Patients with current depression had bilaterally reduced grey matter in the hippocampus compared with HC and untreated patients in stable remission with the latter groups not differing. An increase in grey matter was observed in the hippocampus following treatment with citalopram in currently depressed patients. Grey matter reduction in the hippocampus appears specific to the depressed state and is a potential biomarker for a depressive episode.

Predictors of willingness to receive updated 2023-2024 COVID-19 booster vaccines among a convenience sample in Minnesota.

OBJECTIVES: To determine factors associated with intention to receive recommended COVID-19 booster vaccines in 2023-2024. METHODS: A cross-sectional study of 1,256 individuals at Minnesota State and County fairs was conducted to assess their intention to receive a COVID-19 booster vaccine in the coming year if recommended. The association between booster intention and multiple factors believed to influence willingness to receive the vaccine, including perceived vaccine safety, perceived risk of COVID-19, public health knowledge, fear of future pandemics, and political affiliation, were analyzed using ordinal logistic regression and adjusted odds ratios (aOR). RESULTS: Intention to receive a COVID-19 booster vaccine was high among our participants with 56% reporting they were extremely likely to receive the vaccine this year and another 15% reporting that they were likely to do the same. A strong association with getting a booster vaccine was found between perceived vaccine safety (aOR: 15.3, 95% CI: 10.6-22.2), perceived COVID-19 risk (aOR: 3.5, 95% CI: 2.4-5.1), pandemic fear (aOR: 3.4, 95% CI: 2.4-4.8), public health knowledge (aOR: 1.3, 95% CI: 0.9-1.8), and democrat political affiliation (aOR: 2.8, 95%CI: 1.8-4.4). CONCLUSIONS: Our study emphasizes the importance of perceived vaccine safety as a predictor of intention to accept COVID-19 vaccines and highlights the continued need to effectively communicate with the public about the safety of vaccines.

The relative reliability of actively participating and passively observing raters in a simulation-based assessment for selection to specialty training in anaesthesia.

Selection to specialty training is a high-stakes assessment demanding valuable consultant time. In one initial entry level and two higher level anaesthesia selection centres, we investigated the feasibility of using staff participating in simulation scenarios, rather than observing consultants, to rate candidate performance. We compared participant and observer scores using four different outcomes: inter-rater reliability; score distributions; correlation of candidate rankings; and percentage of candidates whose selection might be affected by substituting participants' for observers' ratings. Inter-rater reliability between observers was good (correlation coefficient 0.73-0.96) but lower between participants (correlation coefficient 0.39-0.92), particularly at higher level where participants also rated candidates more favourably than did observers. Station rank orderings were strongly correlated between the rater groups at entry level (rho 0.81, p < 0.001) but weaker at the two higher level centres (rho 0.52, p = 0.018; rho 0.58, p = 0.001). Substituting participants' for observers' ratings had less effect once scores were combined with those from other selection centre stations. Selection decisions for 0-20% of candidates could have changed, depending on the numbers of training posts available. We conclude that using participating raters is feasible at initial entry level only.

Autologous reconstruction of massive enteroatmospheric fistulation with a pedicled subtotal lateral thigh flap.

BACKGROUND: Reconstruction of massive contaminated abdominal wall defects associated with enteroatmospheric fistulation represents a technical challenge. An effective technique that allows closure of intestinal fistulas and reconstruction of the abdominal wall, with a good functional and cosmetic result, has yet to be described. The present study is a retrospective review of simultaneous reconstruction of extensive gastrointestinal tract fistulation and large full-thickness abdominal wall defects, using a novel pedicled subtotal thigh flap. METHODS: The flap, based on branches of the lateral circumflex femoral artery, was used to reconstruct the abdominal wall in six patients who were dependent on artificial nutritional support, with a median (range) of 4·5 (3-23) separate intestinal fistulas, within open abdominal wounds with a surface area of 564·5 (204-792) cm2. Intestinal reconstruction was staged, with delayed closure of a loop jejunostomy. Median follow-up was 93·5 (10-174) weeks. RESULTS: Successful healing occurred in all patients, with no flap loss or gastrointestinal complications. One patient died from complications of sepsis unrelated to the surgical treatment. All surviving patients gained complete nutritional autonomy following closure of the loop jejunostomy. CONCLUSION: Replacement of almost the entire native abdominal wall in patients with massive contaminated abdominal wall defects is possible, without the need for prosthetic material or microvascular free flaps. The subtotal pedicled thigh flap is a safe and effective method of providing definitive treatment for patients with massive enteroatmospheric fistulation.

Natural outbreak of Streptococcus agalactiae (GBS) infection in wild giant Queensland grouper, Epinephelus lanceolatus (Bloch), and other wild fish in northern Queensland, Australia.

Ninety-three giant Queensland grouper, Epinephelus lanceolatus (Bloch), were found dead in Queensland, Australia, from 2007 to 2011. Most dead fish occurred in northern Queensland, with a peak of mortalities in Cairns in June 2008. In 2009, sick wild fish including giant sea catfish, Arius thalassinus (Rüppell), and javelin grunter, Pomadasys kaakan (Cuvier), also occurred in Cairns. In 2009 and 2010, two disease epizootics involving wild stingrays occurred at Sea World marine aquarium. Necropsy, histopathology, bacteriology and PCR determined that the cause of deaths of 12 giant Queensland grouper, three wild fish, six estuary rays, Dasyatis fluviorum (Ogilby), one mangrove whipray, Himantura granulata (Macleay), and one eastern shovelnose ray, Aptychotrema rostrata (Shaw), was Streptococcus agalactiae septicaemia. Biochemical testing of 34 S. agalactiae isolates from giant Queensland grouper, wild fish and stingrays showed all had identical biochemical profiles. The 16S rRNA gene sequences of isolates confirmed all isolates were S. agalactiae; genotyping of selected S. agalactiae isolates showed the isolates from giant Queensland grouper were serotype Ib, whereas isolates from wild fish and stingrays closely resembled serotype II. This is the first report of S. agalactiae from wild giant Queensland grouper and other wild tropical fish and stingray species in Queensland, Australia.

Neurophotonic tools for microscopic measurements and manipulation: status report.

Neurophotonics was launched in 2014 coinciding with the launch of the BRAIN Initiative focused on development of technologies for advancement of neuroscience. For the last seven years, Neurophotonics' agenda has been well aligned with this focus on neurotechnologies featuring new optical methods and tools applicable to brain studies. While the BRAIN Initiative 2.0 is pivoting towards applications of these novel tools in the quest to understand the brain, this status report reviews an extensive and diverse toolkit of novel methods to explore brain function that have emerged from the BRAIN Initiative and related large-scale efforts for measurement and manipulation of brain structure and function. Here, we focus on neurophotonic tools mostly applicable to animal studies. A companion report, scheduled to appear later this year, will cover diffuse optical imaging methods applicable to noninvasive human studies. For each domain, we outline the current state-of-the-art of the respective technologies, identify the areas where innovation is needed, and provide an outlook for the future directions.