Targeting for nonpoint source pollution reduction: A synthesis of lessons learned, remaining challenges, and emerging opportunities.

The ability to identify, target, and treat critical pollution source areas on a landscape is an ongoing challenge for water quality programs that seek to address nonpoint source (NPS) pollution. In this article, we develop a conceptual framework for targeting program design, and review recent experience with the implementation of targeting programs that corresponds with a wide range of program characteristics. Through this review, we emphasize that the complex and locally dependent nature of NPS generation and transport makes it impossible to define a narrow set of rules to guide targeting programs everywhere. Instead, we evaluate key features of NPS targeting in several different contexts, highlighting lessons learned from recent experience. This synthesis of targeting program design and implementation points toward several areas of opportunity for improved NPS policy, however more research is needed to systematically document changes in behavior and pollutant loads. The lack of monitoring data at refined scales presents a major obstacle to targeting program success. This paper synthesizes new opportunities and ongoing challenges for the implementation of targeting in NPS water quality programs.

A prime/boost vaccine platform efficiently identifies CD27 agonism and depletion of myeloid-derived suppressor cells as therapies that rationally combine with checkpoint blockade in ovarian cancer.

Cancer immunotherapies have generated remarkable clinical responses for some patients with advanced/metastatic disease, prompting exploration of rational combination therapies to bolster anti-tumor immunity in patients with limited response or those who experience tumor progression following an initial response to immunotherapy. In contrast to other tumor indications, objective response rates to single-agent PD-1/PD-L1 blockade in ovarian cancer are limited, suggesting a need to identify combinatorial approaches that lead to tumor regression in a setting where checkpoint blockade alone is ineffective. Using a pre-clinical model of aggressive intraperitoneal ovarian cancer, we have previously reported on a heterologous prime/boost cancer vaccine that elicits robust anti-tumor immunity, prolongs survival of tumor-bearing mice, and which is further improved when combined with checkpoint blockade. As tumor control in this model is CD8 + T cell dependent, we reasoned that the prime/boost vaccine platform could be used to explore additional treatment combinations intended to bolster the effects of CD8 + T cells. Using whole tumor transcriptomic data, we identified candidate therapeutic targets anticipated to rationally combine with prime/boost vaccination. In the context of a highly effective cancer vaccine, CD27 agonism or antibody-mediated depletion of granulocytic cells each modestly increased tumor control following vaccination, with anti-PD-1 therapy further improving treatment efficacy. These findings support the use of immunotherapies with well-defined mechanisms(s) of action as a valuable platform for identifying candidate combination approaches for further therapeutic testing in ovarian cancer.

Awareness and use of nonoccupational post-exposure prophylaxis among men who have sex with men in Vancouver, Canada.

OBJECTIVES: Nonoccupational post-exposure prophylaxis (nPEP) is a strategy to reduce the risk of HIV infection in those with high-risk exposure. This study characterized nPEP awareness among gay, bisexual and other men who have sex with men (MSM) in Metro Vancouver, British Columbia, Canada after a pilot nPEP programme established in 2012. METHODS: Momentum Health Study participants were MSM aged ≥16 years recruited via respondent-driven sampling (RDS) who completed a computer-assisted self-interview. Stratifying patients by HIV status, we used multivariable logistic regression with backward selection to identify factors associated with nPEP awareness. All analyses were RDS-adjusted. RESULTS: A total of 51.9% (112 of 173) of HIV-positive and 48.5% (272 of 500) of HIV-negative participants had heard of nPEP. Only 3% (five of 106) of HIV-negative participants who reported recent high-risk sex used nPEP. Generally, nPEP awareness was higher for participants who engaged in sexual activities with increased HIV transmission potential. Factors associated with greater awareness among HIV-negative participants included recent alcohol use, higher communal sexual altruism, previous sexually transmitted infection diagnosis, and greater perceived condom use self-efficacy. Other factors associated with greater awareness among HIV-negative participants included white race/ethnicity, gay sexual identity, more formal education, lower personal sexual altruism, and Vancouver residence. Greater nPEP awareness among HIV-positive participants was associated with greater perceived agency to ask sexual partners' HIV status and more frequently reporting doing so, a higher number of lifetime receptive sex partners, and greater access to condoms. CONCLUSIONS: Following implementation of an nPEP pilot programme, nPEP awareness among HIV-negative MSM was 51% and use was 3%. These data support the need to expand access to and actively promote nPEP services.

Validity and reliability of the behavioral signs of respiratory instability (BSRI) © scale during activity for infants with bronchopulmonary dysplasia.

OBJECTIVE: There is no reliable evidence on how best to evaluate the overall status of infants with severe forms of bronchopulmonary dysplasia (BPD). The Behavioral Signs of Respiratory Instability (BSRI) scale was developed as an objective measure of developmental capacity during occupational and physical therapy sessions. The purpose of this study was to determine the psychometric properties of the BSRI Scale. STUDY DESIGN: The BSRI and Respiratory Severity Score (RSS) were compared for 25 infants with BPD and 15 infants without BPD. A cross-sectional design was used to test inter-rater reliability among 10 NICU occupational and physical therapists. A prospective cohort design was used to evaluate validity. RESULTS: The BSRI demonstrated good to excellent inter-rater reliability (ρ = 0.47-0.91) and was strongly correlated with RSS (ρ = -0.77, p < 0.001; concurrent validity). CONCLUSION: The BSRI Scale has preliminary psychometric support. Standardized measures like the BSRI may provide accurate, objective data that can improve care planning within interdisciplinary teams that supports brain growth and potentially improves neurodevelopment.

The UK national registry of ENT surgeons with coronavirus disease 2019: one year on.

OBJECTIVES: To report the one-year findings of the UK national registry of ENT surgeons with suspected or confirmed coronavirus disease 2019, and the results of a survey on the coronavirus disease 2019 experience of UK ENT trainees. METHOD: An online registry was created in April 2020. A separate survey was circulated electronically to all members of the Association of Otolaryngologists in Training. RESULTS: The registry recorded 98 clinicians with confirmed or suspected coronavirus disease 2019. The majority of infections were reported in the first wave of spring 2020. Two ENT surgeons were hospitalised and one died. The majority suspected workplace exposure, with a significant proportion attributing this to a lack of personal protective equipment at a time before formal guidance had been introduced. Of the ENT trainees surveyed, almost one-third believed that they had contracted coronavirus disease 2019. CONCLUSION: This highlights the importance of ongoing risk-reduction measures, including optimal personal protective equipment and vaccination.

Development and operation of the defence COVID-19 lab as a SARS-CoV-2 diagnostic screening capability for UK military personnel.

BACKGROUND: In the face of the COVID-19 pandemic, the Defence Science and Technology Laboratory (Dstl) and Defence Pathology combined to form the Defence Clinical Lab (DCL), an accredited (ISO/IEC 17025:2017) high-throughput SARS-CoV-2 PCR screening capability for military personnel. LABORATORY STRUCTURE AND RESOURCE: The DCL was modular in organisation, with laboratory modules and supporting functions combining to provide the accredited SARS-CoV-2 (envelope (E)-gene) PCR assay. The DCL was resourced by Dstl scientists and military clinicians and biomedical scientists. LABORATORY RESULTS: Over 12 months of operation, the DCL was open on 289 days and tested over 72 000 samples. Six hundred military SARS-CoV-2-positive results were reported with a median E-gene quantitation cycle (Cq) value of 30.44. The lowest Cq value for a positive result observed was 11.20. Only 64 samples (0.09%) were voided due to assay inhibition after processing started. CONCLUSIONS: Through a sustained effort and despite various operational issues, the collaboration between Dstl scientific expertise and Defence Pathology clinical expertise provided the UK military with an accredited high-throughput SARS-CoV-2 PCR test capability at the height of the COVID-19 pandemic. The DCL helped facilitate military training and operational deployments contributing to the maintenance of UK military capability. In offering a bespoke capability, including features such as testing samples in unit batches and oversight by military consultant microbiologists, the DCL provided additional benefits to the UK Ministry of Defence that were potentially not available from other SARS-CoV-2 PCR laboratories. The links between Dstl and Defence Pathology have also been strengthened, benefitting future research activities and operational responses.

The Use of Oral Midazolam to Facilitate the Ophthalmic Examination of Children with Autism and Developmental Disorders.

Ophthalmic examinations of developmentally delayed/autistic children are challenging. Oral midazolam may be a viable alternative to general anaesthesia for this indication. Single-centre retrospective cohort study (January 2018-March 2020). Oral midazolam (0.5 mg/kg, max 15 mg). Metrics included: patient demographics, examination completion rate, duration of stay and adverse events. 50 oral midazolam examinations were performed (45 patients). Mean age was 79.12 months. All had developmental delay (66.67% autism). Time to ophthalmic examination was 60.31 minutes. Eye examination was successfully completed in 98%. No adverse events were reported. Mean stay was 3.35 hours. Oral midazolam (0.5 mg/kg, max 15 mg) is associated with safe, successful completion of ophthalmic examinations in children previously unexaminable in clinic.

Adjuvant oncolytic virotherapy for personalized anti-cancer vaccination.

By conferring systemic protection and durable benefits, cancer immunotherapies are emerging as long-term solutions for cancer treatment. One such approach that is currently undergoing clinical testing is a therapeutic anti-cancer vaccine that uses two different viruses expressing the same tumor antigen to prime and boost anti-tumor immunity. By providing the additional advantage of directly killing cancer cells, oncolytic viruses (OVs) constitute ideal platforms for such treatment strategy. However, given that the targeted tumor antigen is encoded into the viral genomes, its production requires robust infection and therefore, the vaccination efficiency partially depends on the unpredictable and highly variable intrinsic sensitivity of each tumor to OV infection. In this study, we demonstrate that anti-cancer vaccination using OVs (Adenovirus (Ad), Maraba virus (MRB), Vesicular stomatitis virus (VSV) and Vaccinia virus (VV)) co-administered with antigenic peptides is as efficient as antigen-engineered OVs and does not depend on viral replication. Our strategy is particularly attractive for personalized anti-cancer vaccines targeting patient-specific mutations. We suggest that the use of OVs as adjuvant platforms for therapeutic anti-cancer vaccination warrants testing for cancer treatment.

The UK national registry of ENT surgeons with coronavirus disease 2019.

BACKGROUND: ENT surgeons are likely to be at high risk of coronavirus disease 2019 exposure. METHODS: A national registry of UK ENT surgeons with suspected or confirmed coronavirus disease 2019 was created with the support of ENT UK. Voluntary entry was made by either the affected individual or a colleague, using a web-based platform. RESULTS: A four-month data collection period is reported, comprising 73 individuals. Coronavirus disease 2019 was test-confirmed in 35 respondents (47.9 per cent). There was a need for hospitalisation in two cases (2.7 per cent) and tragically one individual died. Symptom onset peaked in March. The majority suspected their exposure to have been in the workplace, with a significant proportion attributing their disease to a lack of personal protective equipment at a time before formal guidance had been introduced. CONCLUSION: The registry suggests that a significant number of ENT clinicians in the UK have contracted coronavirus disease 2019, and supports the need for tailored personal protective equipment guidance and service planning.

Barriers to research among residents in Otolaryngology - Head & Neck Surgery around the world.

OBJECTIVES: To document the challenges faced by residents in Otolaryngology - Head & Neck Surgery (OTL-HNS) around the world to successfully complete research projects. The second objective is to assess if the challenges are uniform worldwide. METHODS: A survey was sent to all OTL-HNS under 45 years old from the 2017 IFOS meeting. This survey was conducted by the YO-IFOS group (Young Otolaryngologists of the International Federation of Otolaryngological Societies). Data was collected for a period of 1 month. Demographic characteristics, information regarding research projects conducted and data concerning perceived barriers to completion of research projects were collected. RESULTS: Among the 2787 attendees, 928 responded to the survey (response rate=33.3%). Of these 928 answers, 267 responses were from residents/interns in OTL-HNS, while 635 responses were from certified otolaryngologists. The three most frequent obstacles to conducting research projects for trainees were limited dedicated time (64%), insufficient financial resources (55%) and lack of education in research (45%). There was no statistical difference in these barriers among the different countries (P>0.05). CONCLUSION: This is the first international study that provides insight on trainee's challenges to conduct research projects during residency. Despite the notion that research is essential for generating new knowledge to guide patient care, many residents fail to successfully incorporate research in their surgical curriculum. These obstacles must be addressed by Otolaryngology - Head & Neck Surgery programs in order to facilitate and support resident's research.

Time-course analyses addressing the acquisition of DBA lectin reactivity in mouse lymphoid organs and uterus during the first week of pregnancy.

Terminal differentiation of uterine natural killer (uNK) cells is induced in humans and mice at the time of endometrial decidualization. In mice, commitment to this lineage is first recognized at gestation day (gd)5.5 when small, non-granulated lymphocytes in the mesometrial decidua basalis become histochemically reactive with the lectin Dolichlos biflorus agglutinin (DBA). Transplantation experiments in mice have shown that the self-renewing progenitors of uNK cells are present in peripheral rather than uterine tissues. While lymphoid tissues of virgin mice lack DBA lectin reactive putative uNK cell precursors or progenitors, peripheral organs have not been systematically examined in female mice during early pregnancy while the uNK cell population is becoming established. Here we report such a study in gd0.5-7.5 random bred mice. Only mesenteric lymph nodes showed a transient gain in DBA lectin reactive lymphocytes between gd0.5 and 4.5. These cells had cytoplasmic but almost no surface DBA lectin reactivity. This study indicates that the decidual environment is unique and locally promotes DBA lectin surface expression in terminally differentiating uNK cells.

Global Professional Behaviours and Networking Preferences of Young Otolaryngologists - An International Survey.

AIMS: An international survey was conducted to explore the professional and regional spread of "young" otolaryngologists, their society membership and networking preferences, with relevance to global health and future initiatives. MATERIAL AND METHODS: Otolaryngologists under the age of 45 years who had attended the 2017 International Federation of Otorhinolaryngological Societies (IFOS) meeting were invited by e-mail to participate in an online survey. Basic demographic data and information regarding career geography and networking preferences was requested. RESULTS: A total of 928 responses (including 635 certified otolaryngologists and 268 trainees) were received from 2787 individuals invited to complete the survey. The overall response rate was 33.3%. Most otolaryngologists were based in an academic hospital. The spread of respondents likely reflects the European location of the meeting from which participants were identified; 61.2% of all respondents were based in Europe. International movement between career stages was evident. The principal preferred networking methods involved face-to-face contact whilst social media use was the method of choice for 13%. CONCLUSION: This survey offers a present-day snapshot and is hoped to serve as a platform for further work. Little is known on a global scale regarding the professional behaviours and networking preferences of otolaryngologists. A greater understanding will facilitate not only education and research but also enable networking and global health work.

Computed tomography versus magnetic resonance imaging in paediatric cochlear implant assessment: a pilot study and our experience at Great Ormond Street Hospital.

BACKGROUND: To date, there is a lack of consensus regarding the use of both computed tomography and magnetic resonance imaging in the pre-operative assessment of cochlear implant candidates. METHODS: Twenty-five patients underwent high-resolution computed tomography and magnetic resonance imaging. 'Control scores' describing the expected visualisation of specific features by computed tomography and magnetic resonance imaging were established. An independent radiological review of all computed tomography and magnetic resonance imaging scan features was then compared to the control scores and the findings recorded. RESULTS: Agreement with control scores occurred in 83 per cent (20 out of 24) of computed tomography scans and 91 per cent (21 out of 23) of magnetic resonance imaging scans. Radiological abnormalities were demonstrated in 16 per cent of brain scans and 18 per cent of temporal bone investigations. CONCLUSION: Assessment in the paediatric setting constitutes a special situation given the likelihood of congenital temporal bone abnormalities and associated co-morbidities that may be relevant to surgery and prognosis following cochlear implantation. Both computed tomography and magnetic resonance imaging contribute valuable information and remain necessary in paediatric cochlear implant pre-operative assessment.

Paediatric tracheostomy tubes: recent developments and our current practice.

OBJECTIVE: A variety of paediatric tracheostomy tubes are available. This article reviews the tubes in current use at Great Ormond Street Hospital for Children and Evelina London Children's Hospital. METHODS: This paper outlines our current preferences, and the particular indications for different tracheostomy tubes, speaking valves and other attachments. RESULTS: Our preferred types of tubes have undergone significant design changes. This paper also reports further experience with certain tubes that may be useful in particular circumstances. An updated sizing chart is included for reference purposes. CONCLUSION: The choice of a paediatric tracheostomy tube remains largely determined by individual clinical requirements. Although we still favour a small range of tubes for use in the majority of our patients, there are circumstances in which other varieties are indicated.

Effect of colony stimulating factor on murine macrophages. Induction of antitumor activity.

Colony stimulating factor (CSF) was assessed for its capacity to stimulate antitumor activity in macrophages. Murine peritoneal macrophages incubated with CSF for 48 h inhibited [3H[thymidine (TdR) incorporation by P815 tumor cells to approximately 20% of control values. Inhibition of CSF-stimulated macrophages was significantly greater than inhibition by unstimulated macrophages (P less than 0.001). CSF had little direct effect on the proliferation of either tumor cells or macrophages alone, indicating that the antitumor activity of CSF was mediated by macrophages. it is unlikely that impurities in the CSF preparations were responsible for the effect since CSF that had been purified to homogeneity was as active as crude preparations. Furthermore the activity of CSF on macrophages was blocked by addition of purified anti-CSF antibodies. In addition to being tumoristatic, CSF-stimulated macrophages were tumoricidal as determined by a tumor colony growth assay. Tumor cells that had been incubated with CSF-stimulated macrophages showed a significant reduction in tumor colony-forming units (P less than 0.01). Thus, in addition to its effect on hemopoietic stem cells, CSF induces certain effector functions in mature macrophages that may enhance endogenous antitumor host defenses.

Report on an interdisciplinary program for allied health.

CONTEXT: A central recommendation from the Pew Health Commission to educators has been to empower future care providers to function effectively as teams. Administrators and faculty members within a school of allied health sciences thus established an interdisciplinary program where students would learn to function as team members and demonstrate competencies required for practice in diverse, demanding, and continually changing health care environments. Students from five disciplines have participated in featured events, mentored activities and capstone projects, earning credit in an interdisciplinary course of study that complements offerings in their home disciplines. GOAL: This follow-up article reports on the progress and development since 2002 of an interdisciplinary program known as Team IDEAL. Formative evaluation measures used to assess satisfaction with the program are presented alongside a discussion of new directions. CONCLUSION: Team IDEAL will move forward in a streamlined form that reflects its central aim. IDEAL leadership will remain cognizant of the effects of discipline-specific curricular changes, complex programming, and student perspectives on the process interdisciplinary education.

Transoral laser resection of glottic carcinoma: what is the significance of anterior commissure involvement?

BACKGROUND: The optimal management of glottic carcinoma involving the anterior commissure is controversial. METHOD: A retrospective analysis was conducted of 76 patients with glottic squamous cell carcinoma treated by transoral carbon dioxide laser resection by a single surgeon. RESULTS: Sixty-three patients (with tumour stage Tis-T3) were eligible for inclusion. Thirty patients had involvement of the anterior commissure; these patients were significantly more likely to have either uncertain or positive margins (63.3 vs 30.3 per cent, p = 0.012), and were also more likely to receive adjuvant radiotherapy (40 vs 3.2 per cent, p = 0.0005). The overall laryngeal preservation rate was 96.8 per cent; there was no statistically significant difference between those with and without anterior commissure involvement (96.7 and 96.9 per cent respectively). CONCLUSION: Transoral laser resection with the use of adjuvant radiotherapy in a minority of patients with adverse pathological findings can be recommended for the primary treatment of anterior commissure glottic cancer from an oncological perspective; excellent local control and laryngeal preservation rates can be achieved.

Giant maxillary gingival fibromatosis.

We present a case of both unusual pathology and severity - giant maxillary gingival fibromatosis - and discuss the disease and its management, accompanied by clinical imaging. This represents an overlap between maxillofacial and oral surgery, and may present as demonstrated in this case.

Paediatric injection medialisation laryngoplasty: Recent Great Ormond Street Hospital experience.

INTRODUCTION: Unilateral vocal fold paresis may significantly impair the vocal quality and laryngeal competence of a child. Relatively little literature relates to injection medialisation laryngoplasty (IML) in children and previous reports have involved small numbers of heterogenous cases. METHODS: A retrospective review was conducted of paediatric patients managed by our multidisciplinary specialist voice clinic undergoing IML for unilateral vocal fold paresis. Cases of bilateral paresis, those characterised by vocal fold fixation, and patients without formal pre and post-operative voice evaluation were excluded. RESULTS: Eighteen IML procedures were performed in 12 children eligible for inclusion between 2005 and 2015. The average age at time of procedure was 12 years (range 9-15 years). Autologous fat was used in 5 procedures, succeeded by calcium hydroxylapatite (Radiesse® Voice) from 2011 (n = 13). A significant improvement in median GRBAS score components was observed after calcium hydroxylapatite injection in terms of grade (p = 0.008), breathiness (p = 0.002) and aesthenia (p = 0.016). A pre- and post-procedural Voice Handicap Index was self-completed by 6 patients receiving calcium hydroxylapatite injection; the median change in score was an improvement of 19 points (interquartile range 36.5). CONCLUSION: We describe the outcomes of a comparatively large paediatric series and have found IML using calcium hydroxylapatite to be a reliable technique associated with improved subjective outcome measures. Management of UVCP in the child is a challenge with particular investigative and interventional considerations. Further study supported by high quality subjective and, where possible, objective outcome measures, is required to better inform patient selection, timing of intervention and choice of injection material.

Protein modifications induced in mouse epidermis by potent and weak tumor-promoting hyperplasiogenic agents.

Two-dimensional gel electrophoresis was used to compare the changes in mouse epidermal proteins induced by the potent tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), by the moderate promoter mechanical abrasion, and by the weakly promoting hyperplasiogenic agents mezerein and ethylphenylpropiolate. Evidence is presented which indicates that TPA caused many changes in the epidermal protein profiles especially related to the keratins which are the major differentiation product of the epidermis. The keratin modification progresses with time after TPA treatment, resulting in a keratin pattern which resembles that of newborn mouse epidermis. The criteria used for the identification of the keratins were extractability, isoelectric points, molecular weights, filament formation in vitro, immunological cross-reactivity, amino acid composition, and peptide mapping. Several other protein changes were evident in the more soluble epidermal proteins which were also prominent in the newborn epidermis. These protein alterations are observed not only early during the TPA induction of hyperplasia and inflammation at 48 and 72 hr but also in 1- and 2-week samples in which the morphology of the epidermis has returned to normal. Mezerein and abrasion produced protein changes similar to those induced by TPA. Ethylphenylpropiolate-induced protein modifications not only occurred at later times compared with either mezerein or TPA but also were less in magnitude. However, although many of the protein modifications induced by TPA appear to be associated with the hyperplasiogenic properties of TPA, the major difference between a potent promoter like TPA and a weak promoter like ethylphenylpropiolate appeared to be related to the magnitude of the response and the time of appearance of the protein changes.