SARS-CoV-2 infection in central North Carolina: Protocol for a population-based longitudinal cohort study and preliminary participant results

Public health surveillance systems likely underestimate the true prevalence and incidence of SARS-CoV-2 infection due to limited access to testing and the high proportion of subclinical infections in community-based settings. This ongoing prospective, observational study aimed to generate accurate estimates of the prevalence and incidence of, and risk factors for, SARS-CoV-2 infection among residents of a central North Carolina county. From this cohort, we collected survey data and nasal swabs every two weeks and venous blood specimens every month. Nasal swabs were tested for the presence of SARS-CoV-2 virus (evidence of active infection), and serum specimens for SARS-CoV-2-specific antibodies (evidence of prior infection). As of June 23, 2021, we have enrolled a total of 153 participants from a county with an estimated 76,285 total residents. The anticipated study duration is at least 24 months, pending the evolution of the pandemic. Study data are being shared on a monthly basis with North Carolina state health authorities and future analyses aim to compare study data to state-wide metrics over time. Overall, the use of a probability-based sampling design and a well-characterized cohort will enable collection of critical data that can be used in planning and policy decisions for North Carolina and may be informative for other states with similar demographic characteristics

Reply to 'Comment on 'Efficacy and toxicity of treatment with the anti-CTLA-4 antibody ipilimumab in patients with metastatic melanoma after prior anti-PD-1 therapy''.

Background: Recent phase III clinical trials have established the superiority of the anti-PD-1 antibodies pembrolizumab and nivolumab over the anti-CTLA-4 antibody ipilimumab in the first-line treatment of patients with advanced melanoma. Ipilimumab will be considered for second-line treatment after the failure of anti-PD-1 therapy. Methods: We retrospectively identified a cohort of 40 patients with metastatic melanoma who received single-agent anti-PD-1 therapy with pembrolizumab or nivolumab and were treated on progression with ipilimumab at a dose of 3 mg kg(-1) for a maximum of four doses. Results: Ten percent of patients achieved an objective response to ipilimumab, and an additional 8% experienced prolonged (>6 months) stable disease. Thirty-five percent of patients developed grade 3-5 immune-related toxicity associated with ipilimumab therapy. The most common high-grade immune-related toxicity was diarrhoea. Three patients (7%) developed grade 3-5 pneumonitis leading to death in one patient. Conclusions: Ipilimumab therapy can induce responses in patients who fail the anti-PD-1 therapy with response rates comparable to previous reports. There appears to be an increased frequency of high-grade immune-related adverse events including pneumonitis that warrants close surveillance

Intrinsic factors influence the attachment of fragments of the green alga Caulerpa filiformis

Asexual reproduction via fragmentation is an integral component of the life history of many marine organisms. In south-eastern Australia the green macroalga Caulerpa filiformis (Suhr) Hering is abundant on many rocky shorelines and fragments are very abundant in the water column. We examined some of the factors that may influence the growth and successful reattachment of fragments of C. filiformis that potentially contribute to its success. Field surveys revealed that C. filiformis fragments were of variable morphologies (from small fronds to entire thalli) and sizes (0.1–60 cm in length). All fragments of C. filiformis were viable propagules that survived and grew well in the laboratory. However, some fragments grew more than others, in particular larger sizes (7.5 cm class) of certain morphologies (fragments that consisted only of a single frond). Rhizoids were produced by all fragments, but again, larger fragments produced more rhizoids than smaller fragments. The force required to detach fragments was proportional to the number (but not size) of rhizoids, demonstrating the importance of rhizoids for attachment. The rate of attachment of fragments was also fast, usually within 12 h, but the longer these fragments were attached to a substratum the greater the force required to dislodge them. Interestingly, fragments only produced rhizoids if they were resting on a substratum which may explain the small proportion of fragments with rhizoids in the field (< 5%). Ultimately, the long term success of C. filiformis fragments was low as only 1.6% of fragments attached within 24 h and none of these persisted for longer than 2 days. Nonetheless, the abundance and viability of fragments of C. filiformis available to attach suggest that asexual fragmentation is a successful reproductive strategy in this seaweed

System-Agnostic Security Domains for Understanding and Prioritizing Systems Security Engineering Efforts

As modern systems continue to increase in size and complexity, current systems security practices lack an effective approach to prioritize and tailor systems security efforts to successfully develop and field systems in challenging operational environments. This paper uniquely proposes seven system-agnostic security domains, which assist in understanding and prioritizing systems security engineering (SSE) efforts. To familiarize the reader with the state-of-the-art in SSE practices, we first provide a comprehensive discussion of foundational SSE concepts, methodologies, and frameworks. Next, the seven system-agnostic security domains are presented for consideration by researchers and practitioners. The domains are intended to be representative of a holistic SSE approach, which is universally applicable to multiple systems classes and not just a single-system implementation. Finally, three examples are explored to illustrate the utility of the system-agnostic domains for understanding and prioritizing SSE efforts in information technology systems, Department of Defense weapon systems, and cyber-physical systems

A Customizable Framework for Prioritizing Systems Security Engineering Processes, Activities, and Tasks

As modern systems become increasingly complex, current security practices lack effective methodologies to adequately address the system security. This paper proposes a repeatable and tailorable framework to assist in the application of systems security engineering (SSE) processes, activities, and tasks as defined in the recently released National Institute of Standards and Technology (NIST) Special Publication 800-160. First, a brief survey of systems-oriented security methodologies is provided. Next, an examination of the relationships between the NIST-defined SSE processes is conducted to provide context for the engineering problem space. These findings inform a mapping of the NIST SSE processes to seven system-agnostic security domains which enable prioritization for three types of systems (conventional IT, cyber-physical, and defense). These concrete examples provide further understanding for applying and prioritizing the SSE effort. The goal of this paper is assist practitioners by informing the efficient application of the 30 processes, 111 activities, and 428 tasks defined in NIST SP 800-160. The customizable framework tool is available online for developers to employ, modify, and tailor to meet their needs