Conserving ecosystem integrity: Ecological theory as a guide for marine protected area monitoring.

Global policies increasingly focus on the importance of maintaining or improving the integrity of ecosystems, but defining, assessing, and monitoring integrity in marine protected areas (MPAs) remains a challenge. In this paper, we conceptualized ecological integrity along dimensions of heterogeneity and stability containing seven components: physical structure, diversity, function, persistence, resistance, resilience, and natural variability. Through a structured literature search, we identified indicators and metrics used for quantifying ecosystem status components in the marine environment, then reviewed MPA management plans worldwide for inclusion of these components. We evaluated 202 papers applying 83 ecological indicators built from 72 metrics. Ecosystem components were most comprehensively addressed by metrics of taxa presence, organisms count, and area occupied by benthic organisms, and community structure, biomass, and percent cover indicators. Of the 557 MPA management plans we reviewed globally, 93% used at least one ecosystem status term or its synonym in an ecologically relevant context, but 39% did not address any components of stability. In particular, resistance was mentioned in only 1% of management plans, but in some cases it may be inferred from indicators and metrics used to track the best addressed component in management plans, diversity. Plans for MPAs with both an ecological/biological purpose and a research and education purpose contained ecosystem status terms more frequently than other plans, suggesting that engagement with the scientific community may have improved the application of these terms. An improved understanding of how to operationalize and measure ecological integrity can help MPA monitoring and management.

Groundfish biodiversity change in northeastern Pacific waters under projected warming and deoxygenation.

In the coming decades, warming and deoxygenation of marine waters are anticipated to result in shifts in the distribution and abundance of fishes, with consequences for the diversity and composition of fish communities. Here, we combine fisheries-independent trawl survey data spanning the west coast of the USA and Canada with high-resolution regional ocean models to make projections of how 34 groundfish species will be impacted by changes in temperature and oxygen in British Columbia (BC) and Washington. In this region, species that are projected to decrease in occurrence are roughly balanced by those that are projected to increase, resulting in considerable compositional turnover. Many, but not all, species are projected to shift to deeper depths as conditions warm, but low oxygen will limit how deep they can go. Thus, biodiversity will likely decrease in the shallowest waters (less than 100 m), where warming will be greatest, increase at mid-depths (100-600 m) as shallow species shift deeper, and decrease at depths where oxygen is limited (greater than 600 m). These results highlight the critical importance of accounting for the joint role of temperature, oxygen and depth when projecting the impacts of climate change on marine biodiversity. This article is part of the theme issue 'Detecting and attributing the causes of biodiversity change: needs, gaps and solutions'.

Changes in preterm birth and stillbirth during COVID-19 lockdowns in 26 countries.

Preterm birth (PTB) is the leading cause of infant mortality worldwide. Changes in PTB rates, ranging from -90% to +30%, were reported in many countries following early COVID-19 pandemic response measures ('lockdowns'). It is unclear whether this variation reflects real differences in lockdown impacts, or perhaps differences in stillbirth rates and/or study designs. Here we present interrupted time series and meta-analyses using harmonized data from 52 million births in 26 countries, 18 of which had representative population-based data, with overall PTB rates ranging from 6% to 12% and stillbirth ranging from 2.5 to 10.5 per 1,000 births. We show small reductions in PTB in the first (odds ratio 0.96, 95% confidence interval 0.95-0.98, P value <0.0001), second (0.96, 0.92-0.99, 0.03) and third (0.97, 0.94-1.00, 0.09) months of lockdown, but not in the fourth month of lockdown (0.99, 0.96-1.01, 0.34), although there were some between-country differences after the first month. For high-income countries in this study, we did not observe an association between lockdown and stillbirths in the second (1.00, 0.88-1.14, 0.98), third (0.99, 0.88-1.12, 0.89) and fourth (1.01, 0.87-1.18, 0.86) months of lockdown, although we have imprecise estimates due to stillbirths being a relatively rare event. We did, however, find evidence of increased risk of stillbirth in the first month of lockdown in high-income countries (1.14, 1.02-1.29, 0.02) and, in Brazil, we found evidence for an association between lockdown and stillbirth in the second (1.09, 1.03-1.15, 0.002), third (1.10, 1.03-1.17, 0.003) and fourth (1.12, 1.05-1.19, <0.001) months of lockdown. With an estimated 14.8 million PTB annually worldwide, the modest reductions observed during early pandemic lockdowns translate into large numbers of PTB averted globally and warrant further research into causal pathways.

Association Between Delayed Discharge From Acute Care and Rehabilitation Outcomes and Length of Stay: A Retrospective Cohort Study.

OBJECTIVE: To examine the association between discharge delays from acute to rehabilitation care because of capacity strain in the rehabilitation units, patient length of stay (LOS), and functional outcomes in rehabilitation. DESIGN: Retrospective cohort study using an instrumental variable to remove potential biases because of unobserved patient characteristics. SETTING: Two campuses of a hospital network providing inpatient acute and rehabilitation care. PARTICIPANTS: Patients admitted to and discharged from acute care categories of Medicine and Neurology/Musculoskeletal (Neuro/MSK) and subsequently admitted to and discharged from inpatient rehabilitation between 2013 and 2019 (N=10486). INTERVENTIONS: None. MAIN OUTCOME MEASURES: Rehabilitation LOS, FIM scores at admission and discharge, and rehabilitation efficiency defined as FIM score improvement per day of rehabilitation. RESULTS: The final cohort contained 3690 records for Medicine and 1733 for Neuro/MSK categories. For Medicine, 1 additional day of delayed discharge was associated with an average 5.1% (95% confidence interval [CI], 3%-7.3%) increase in rehabilitation LOS and 0.08 (95% CI, 0.03-0.13) reduction in rehabilitation efficiency. For Neuro/MSK, 1 additional day of delayed discharge was associated with an average 11.6% (95% CI, 2.8%-20.4%) increase in rehabilitation LOS and 0.08 (95% CI, -0.07 to 0.23) reduction in rehabilitation efficiency. CONCLUSIONS: Delayed discharge from acute care to rehabilitation because of capacity strain in rehabilitation had a strong association with prolonged LOS in rehabilitation. An important policy implication of this "cascading" effect of delays is that reducing capacity strain in rehabilitation could be highly effective in reducing discharge delays from acute care and improving rehabilitation efficiency.

Illuminating and mitigating the evolving impacts of COVID-19 on ethnocultural communities: a participatory action mixed-methods study.

BACKGROUND: The COVID-19 pandemic has exacerbated disparities in poverty and illness for people in vulnerable circumstances in ethnocultural communities. We sought to understand the evolving impacts of COVID-19 on ethnocultural communities to inform intersectoral advocacy and community action. METHODS: The Illuminate Project used participatory action research, with cultural health brokers as peer researchers, from Sept. 21 to Dec. 31, 2020, in Edmonton, Alberta. Twenty-one peer researchers collected narratives from members of ethnocultural communities and self-interpreted them as they entered the narratives into the SenseMaker platform, a mixed-method data collection tool. The entire research team analyzed real-time, aggregate, quantitative and qualitative data to identify emerging thematic domains, then visualized these domains with social network analysis. RESULTS: Brokers serving diverse communities collected 773 narratives. Identified domains illuminate the evolving and entangled impacts of COVID-19 including the following: COVID-19 prevention and management; care of acute, chronic and serious illnesses other than COVID-19; maternal care; mental health and triggers of past trauma; financial insecurity; impact on children and youth and seniors; and legal concerns. We identified that community social capital and cultural brokering are key assets that facilitate access to formal health and social system supports. INTERPRETATION: The Illuminate Project has illustrated the entangled, systemic issues that result in poor health among vulnerable members of ethnocultural communities, and the exacerbating effects of COVID-19, which also increased barriers to mitigation. Cultural brokering and community social capital are key supports for people during the COVID-19 pandemic. These findings can inform policy to reduce harm and support community resiliency.

Fish harvesting advice under climate change: A risk-equivalent empirical approach.

The rate of climate change (CC) has accelerated to the point where it now affects the mid- to long-term sustainability of fishing strategies. Therefore, it is important to consider practical and effective ways to incorporate CC into fisheries advice so that the advice can be considered conditioned to CC. We developed a model to characterise the empirical relationship between a variable affected by climate and fish production. We then used model projections as a foundation for a risk analysis of CC effects on harvesting of Greenland halibut Reinhardtius hippoglossoides in the Gulf of St Lawrence, Canada. The risk-based approach quantified a) the relative change in risk of a status quo fishing strategy under various CC scenarios, and b) the change in fishery exploitation rates required to achieve a management objective over a specified time period at a level of risk considered acceptable (risk equivalent fishery exploitation advice). This empirical approach can be used to develop risk-based advice for any other external variable that affects stock production in addition to climate-related variables and it can be applied in most situations where there is an index of stock biomass and fisheries catch. Shifting the focus from process-based understanding of the responses of fish stocks to CC to quantification of how CC-contributed uncertainty can alter the risks associated with different fishing strategies and/or management options, can ensure timely delivery of robust scientific advice for fisheries under non-stationary environmental conditions.

Changes in ocean health in British Columbia from 2001 to 2016.

Effective management of marine systems requires quantitative tools that can assess the state of the marine social-ecological system and are responsive to management actions and pressures. We applied the Ocean Health Index (OHI) framework to retrospectively assess ocean health in British Columbia annually from 2001 to 2016 for eight goals that represent the values of British Columbia's coastal communities. We found overall ocean health improved over the study period, from 75 (out of 100) in 2001 to 83 in 2016, with scores for inhabited regions ranging from 68 (North Coast, 2002) to 87 (West Vancouver Island, 2011). Highest-scoring goals were Tourism & Recreation (average 94 over the period) and Habitat Services (100); lowest-scoring goals were Sense of Place (61) and Food Provision (64). Significant increases in scores over the time period occurred for Food Provision (+1.7 per year), Sense of Place (+1.4 per year), and Coastal Livelihoods (+0.6 per year), while Habitat Services (-0.01 per year) and Biodiversity (-0.09 per year) showed modest but statistically significant declines. From the results of our time-series analysis, we used the OHI framework to evaluate impacts of a range of management actions. Despite challenges in data availability, we found evidence for the ability of management to reduce pressures on several goals, suggesting the potential of OHI as a tool for assessing the effectiveness of marine resource management to improve ocean health. Our OHI assessment provides an important comprehensive evaluation of ocean health in British Columbia, and our open and transparent process highlights opportunities for improving accessibility of social and ecological data to inform future assessment and management of ocean health.

Annual hearing screening in girls with Turner Syndrome: Results from the first three years in Glasgow.

BACKGROUND: Hearing loss is prevalent in girls with Turner Syndrome (TS). A number of cross-sectional studies have confirmed that conductive hearing loss due to middle ear disease and permanent, progressive sensorineural hearing loss are both very common and often unrecognised in TS. Hearing screening has been suggested by many authors and is recommended in some recent national audiology guidelines (every 3-5 years in an international consensus statement, every 1-2 years in the USA and every year in the UK). The effectiveness of such regular hearing screening has not been assessed before. STUDY AIMS AND METHODS: In January 2016 we began a programme of annual hearing screening for all girls attending the West of Scotland TS clinic. We have collected data on age, karyotype, ear and hearing symptoms, otoscopy findings, audiometric test results and subsequent outcomes for the first three years of our programme. Our aim is to assess whether this screening programme is an effective use of resources, with a worthwhile rate of detecting new otological problems and without an excessive additional workload for the audiology department. RESULTS: Twenty-six girls participated in the screening programme and 8 of these had no hearing issues or ear abnormalities at any time over the 3 years. Two girls had cholesteatoma, 4 had tympanic membrane retractions and/or perforations, and 9 had OME (of which 6 were transient and 3 persistent, with 2 of these requiring treatment). One cholesteatoma, one perforation and one persistent OME were already known about but all other diagnoses were new as a result of the screening programme. Five girls have persistent conductive hearing loss (plus another 6 who had a transient episode of conductive loss due to middle ear fluid) and 6 have some degree of sensorineural hearing loss (3 purely sensorineural, 3 mixed). At the time that a hearing loss was diagnosed, the parents had concerns about the hearing in 4 cases and no concerns in 12. Six girls have been fitted with hearing aids since we started the screening programme, each for different indications (sensorineural hearing loss in two cases, and one case each of persistent OME, post cholesteatoma surgery, tympanic membrane perforation and unilateral tympanic membrane retraction respectively). Two girls have had ear surgery as a result of referral from the programme (one for ventilation tubes, one for cholesteatoma). CONCLUSIONS: The screening programme has picked up ear disease in 69% of girls with TS with only a small additional workload for the audiology department. The ongoing detection of new problems in the second and third years of the programme attests to the value of continued regular hearing screening for girls with TS.

Distinct functions of macrophage-derived and cancer cell-derived cathepsin Z combine to promote tumor malignancy via interactions with the extracellular matrix.

During the process of tumor progression, cancer cells can produce the requisite growth- and invasion-promoting factors and can also rely on noncancerous cells in the tumor microenvironment as an alternative, cell-extrinsic source. However, whether the cellular source influences the function of such tumor-promoting factors remains an open question. Here, we examined the roles of the cathepsin Z (CtsZ) protease, which is provided by both cancer cells and macrophages in pancreatic neuroendocrine tumors in humans and mice. We found that tumor proliferation was exclusively regulated by cancer cell-intrinsic functions of CtsZ, whereas tumor invasion required contributions from both macrophages and cancer cells. Interestingly, several of the tumor-promoting functions of CtsZ were not dependent on its described catalytic activity but instead were mediated via the Arg-Gly-Asp (RGD) motif in the enzyme prodomain, which regulated interactions with integrins and the extracellular matrix. Together, these results underscore the complexity of interactions within the tumor microenvironment and indicate that cellular source can indeed impact molecular function.

Identification and characterization of poorly differentiated invasive carcinomas in a mouse model of pancreatic neuroendocrine tumorigenesis.

Pancreatic neuroendocrine tumors (PanNETs) are a relatively rare but clinically challenging tumor type. In particular, high grade, poorly-differentiated PanNETs have the worst patient prognosis, and the underlying mechanisms of disease are poorly understood. In this study we have identified and characterized a previously undescribed class of poorly differentiated PanNETs in the RIP1-Tag2 mouse model. We found that while the majority of tumors in the RIP1-Tag2 model are well-differentiated insulinomas, a subset of tumors had lost multiple markers of beta-cell differentiation and were highly invasive, leading us to term them poorly differentiated invasive carcinomas (PDICs). In addition, we found that these tumors exhibited a high mitotic index, resembling poorly differentiated (PD)-PanNETs in human patients. Interestingly, we identified expression of Id1, an inhibitor of DNA binding gene, and a regulator of differentiation, specifically in PDIC tumor cells by histological analysis. The identification of PDICs in this mouse model provides a unique opportunity to study the pathology and molecular characteristics of PD-PanNETs.

The prevalence of ear, nose and throat disorders in preschool children with Down's syndrome in Glasgow.

Guidelines suggest that all children with Down's syndrome have hearing testing on a regular basis. Since 2004, the ear, nose and throat (ENT), audiology and education services have conducted a joint clinic for annual ENT health and hearing surveillance of all preschool children with Down's syndrome in Greater Glasgow. The aim of this study is to report the prevalence of ENT problems in this well-defined birth cohort, and the proportion of children for whom ENT surgery is required. A prospective database has been kept since 2004, detailing the ENT health status of every child attending the community-based surveillance clinic. Between September 2004 and September 2008, 87 preschool (aged 9 months to 6 years) children with Down's syndrome were sent appointments for the clinic. Of these, 48 (55%) were female and 39 were male. Data were available for 79 (91%). Over the course of the study, 37% were listed for surgery at some point, either adenotonsillectomy for obstructive symptoms or grommet insertion for otitis media with effusion (OME). The prevalence of OME was 93% at age 1, falling to 68% by age 5. None had significant sensorineural hearing impairment. Obstructive symptoms were also common, with 79% of children having either currently symptomatic upper airways obstruction or a history of adenotonsillectomy by age 5. One child had laryngomalacia and two had symptomatic congenital subglottic stenosis. The prevalence of ENT problems in these children is high. Surgical intervention is frequently required. We advocate a proactive approach of regular ENT and audiology surveillance leading to early intervention, with the aim of maximizing health and educational achievement in the long term.

IL-4 induces cathepsin protease activity in tumor-associated macrophages to promote cancer growth and invasion.

Innate immune cells can constitute a substantial proportion of the cells within the tumor microenvironment and have been associated with tumor malignancy in patients and animal models of cancer; however, the mechanisms by which they modulate cancer progression are incompletely understood. Here, we show that high levels of cathepsin protease activity are induced in the majority of macrophages in the microenvironment of pancreatic islet cancers, mammary tumors, and lung metastases during malignant progression. We further show that tumor-associated macrophage (TAM)-supplied cathepsins B and S are critical for promoting pancreatic tumor growth, angiogenesis, and invasion in vivo, and markedly enhance the invasiveness of cancer cells in culture. Finally, we demonstrate that interleukin-4 (IL-4) is responsible for inducing cathepsin activity in macrophages in vitro and in vivo. Together, these data establish IL-4 as an important regulator, and cathepsin proteases as critical mediators, of the cancer-promoting functions of TAMs.

Aneuploidy affects proliferation and spontaneous immortalization in mammalian cells.

Aneuploidy, an incorrect number of chromosomes, is the leading cause of miscarriages and mental retardation in humans and is a hallmark of cancer. We examined the effects of aneuploidy on primary mouse cells by generating a series of cell lines that carry an extra copy of one of four mouse chromosomes. In all four trisomic lines, proliferation was impaired and metabolic properties were altered. Immortalization, the acquisition of the ability to proliferate indefinitely, was also affected by the presence of an additional copy of certain chromosomes. Our data indicate that aneuploidy decreases not only organismal but also cellular fitness and elicits traits that are shared between different aneuploid cells.

DARTS 2000 online diabetes management system: formative evaluation in clinical practice.

RATIONALE, AIMS AND OBJECTIVES: Failure to engage in user-informed evaluation of emergent health informatics tools can have negative consequences for future implementation, related both to poor usability or clinical utility and to suboptimal stakeholder buy-in. This paper describes a formative evaluation in primary care of a multifaceted, web-based resource for diabetes management. The primary aims were to assess the usability and utility of the prototype in order to inform system refinements prior to implementation, and to investigate barriers and facilitators to system use so as to aid the development of a tailored implementation plan. METHODS: A mixed-method approach involving survey, remote observation, semi-structured interviews and electronic feedback. CONTEXT: One Scottish local health care cooperative comprising five general practice surgeries and their staff. RESULTS: A survey following temporary exposure to a dummy site revealed high levels of computer familiarity, welcoming attitudes and positive ratings of usability, format and utility. Comments mainly addressed content accuracy, feature suggestions and usability issues. Key barriers and facilitators to use included time and training. Remote observation following access to live clinical data enabled profiling of usage by individual and professional group. In the 3 month observation period administrators were the most frequent users, followed by GPs and nurses, with clinical and data entry screens accessed most often. Semi-structured interviews with key respondents sampled by professional group and usage frequency provided richer qualitative information on barriers and facilitators to use, patterns of system integration into work routines and system usability, content and utility. Content analysis of electronic feedback revealed mainly technical queries and general expressions of satisfaction. CONCLUSIONS: Evaluation informed a number of important and unforeseen improvements to the prototype and helped refine the implementation plan. Engagement in the process of evaluation has led to high levels of stakeholder ownership and widespread implementation.