A general principle governs vision‐dependent dendritic patterning of retinal ganglion cells

Dendritic arbors of retinal ganglion cells (RGCs) collect information over a certain area of the visual scene. The coverage territory and the arbor density of dendrites determine what fraction of the visual field is sampled by a single cell and at what resolution. However, it is not clear whether visual stimulation is required for the establishment of branching patterns of RGCs, and whether a general principle directs the dendritic patterning of diverse RGCs. By analyzing the geometric structures of RGC dendrites, we found that dendritic arbors of RGCs underwent a substantial spatial rearrangement after eye‐opening. Light deprivation blocked both the dendritic growth and the branch patterning, suggesting that visual stimulation is required for the acquisition of specific branching patterns of RGCs. We further showed that vision‐dependent dendritic growth and arbor refinement occurred mainly in the middle portion of the dendritic tree. This nonproportional growth and selective refinement suggest that the late‐stage dendritic development of RGCs is not a passive stretching with the growth of eyes, but rather an active process of selective growth/elimination of dendritic arbors of RGCs driven by visual activity. Finally, our data showed that there was a power law relationship between the coverage territory and dendritic arbor density of RGCs on a cell‐by‐cell basis. RGCs were systematically less dense when they cover larger territories regardless of their cell type, retinal location, or developmental stage. These results suggest that a general structural design principle directs the vision‐dependent patterning of RGC dendrites. J. Comp. Neurol. 522:3403–3422, 2014. © 2014 Wiley Periodicals, Inc.     

Antiretroviral therapy uptake and coverage in four HIV community cohort studies in sub‐Saharan Africa

Objective To compare socio‐demographic patterns in access to antiretroviral therapy (ART) across four community HIV cohort studies in Africa. Methods Data on voluntary counselling and testing and ART use among HIV‐infected persons were analysed from Karonga (Malawi), Kisesa (Tanzania), Masaka (Uganda) and Manicaland (Zimbabwe), where free ART provision started between 2004 and 2007. ART coverage was compared across sites by calculating the proportion on ART among those estimated to need treatment, by age, sex and educational attainment. Logistic regression was used to identify socio‐demographic characteristics associated with undergoing eligibility screening at an ART clinic within 2 years of being diagnosed with HIV, for three sites with information on diagnosis and screening dates. Results Among adults known to be HIV‐infected from serological surveys, the proportion who knew their HIV status was 93% in Karonga, 37% in Kisesa, 46% in Masaka and 25% in Manicaland. Estimated ART coverage was highest in Masaka (68%) and lowest in Kisesa (2%). The proportion of HIV‐diagnosed persons who were screened for ART eligibility within 2 years of diagnosis ranged from 14% in Kisesa to 84% in Masaka, with the probability of screening uptake increasing with age at diagnosis in all sites. Conclusions Higher HIV testing rates among HIV‐infected persons in the community do not necessarily correspond with higher uptake of ART, nor more equitable treatment coverage among those in need of treatment. In all sites, young adults tend to be disadvantaged in terms of accessing and initiating ART, even after accounting for their less urgent need.     

Total Patellar Skin Loss From Cryotherapy After Total Knee Arthroplasty

The use of cryotherapy after total knee arthroplasty is a very common therapeutic adjunct accepted as routine postoperative care. We present 2 cases of total patellar skin loss due to cryotherapy after total knee arthroplasty. Substantial soft tissue defects were created after the initial debridement of the necrotic tissue. Both patients were evaluated for frostbite, and the wounds were sharply debrided. Application of an advanced wound management technique involves the use of a collagen-glycosaminoglycan biodegradable bilayer matrix, silver impregnated antimicrobial dressing, and low-pressure vacuum device, followed by delayed split thickness skin grafting and low-pressure vacuum device. We find that this technique provided durable soft tissue coverage for necrotic wounds of the knee that do not involve the joint capsule.     

School staff as vaccine advocates: Perspectives on vaccine mandates and the student registration process

Recently, several states in the US have made it more difficult to receive nonmedical exemptions to school vaccine mandates in the hope of better orienting parents towards vaccination. However, little is known about how public-facing school staff implement and enforce mandate policies, including why or how often they steer parents towards nonmedical exemptions. This study focused on Michigan, which has recently added an additional burden for families seeking nonmedical exemptions. We used an anonymous online survey to assess Michigan public-school employees (n = 157) about their knowledge, attitudes, and behaviors regarding Michigan’s school enrollment vaccine mandate policy. Our main conclusions are that frontline school staff are generally knowledgeable about vaccines and immunization policy, but are at best ambivalent about their role in immunization governance, believing that other agents should be responsible for ensuring that children are vaccinated. Furthermore, some respondents indicated low vaccine confidence, which was associated with increased ambivalence about, or opposition to, their role in immunization governance. As more jurisdictions within and beyond the US consider introducing or tightening childhood vaccine mandates, it is increasingly important to understand how these policies can be improved by attending to the attitudes and roles of relevant frontline actors.     

Pneumococcal vaccine uptake among Medicare Beneficiaries aged ≥65 years following the shared clinical decision-making recommendation for 13-valent pneumococcal conjugate vaccine in 2019

BackgroundIn November 2019, the US Advisory Committee on Immunization Practices recommended shared clinical decision-making (SCDM) for use of 13-valent pneumococcal conjugate vaccine (PCV13) among immunocompetent elderly adults. The impact of SCDM on PCV13 use in this population, immunocompromised persons, and vulnerable subgroups has not been well documented.MethodsUsing Medicare Research Identifiable Files (01/2018 – 09/2020), monthly uptake of pneumococcal vaccine (PCV13, 23-valent pneumococcal polysaccharide vaccine [PPSV23]) was identified among fee-for-service beneficiaries aged ≥ 65 years with Part B coverage and no evidence of prior PCV13. Uptake was stratified by vaccine, risk profile, and demographics.ResultsAmong the > 12 M beneficiaries included each month, PCV13 uptake declined from > 70% of pneumococcal vaccinations before SCDM to < 60% after SCDM (02/2020). Reductions in PCV13 uptake were consistent across vulnerable subgroups as well as immunocompromised persons.ConclusionsPCV13 use decreased among immunocompetent and immunocompromised persons alike, despite continued routine PCV13 recommendation for the latter group.     

Adherence to vaccination guidelines of patients with complete splenectomy in Norway, 2008–2020

The spleen is responsible for blood filtration and mounting an immune response against pathogens. In some people the spleen must be surgically removed because of traumatic events or oncological and hematological conditions. These patients are at higher risk of developing diseases caused by encapsulated bacteria throughout their lives. Thus, immunisations are advised for splenectomised persons to prevent infection caused by Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae type b (Hib). This study assessed vaccination coverage (VC) among Norwegian patients with surgical asplenia. Using the Nomesco Classification of Surgical Procedures codes, patient information (age, sex, date of initial diagnosis and date of surgery) was acquired from the Norwegian Patient Registry. The National Immunization Register provided information on vaccination status and data of any subsequent invasive bacterial infections were obtained from the Norwegian Surveillance System for Communicable Diseases. From the total population of Norway, 3155 patients who had undergone complete splenectomy were identified. Of these, 914 (29.0%) had received at least one dose of pneumococcal conjugate vaccine (PCV), 1324 (42.0%) at least one dose of pneumococcal polysaccharide vaccine and 589 (18.7%) had received both. Only 4.2% of the patients had received two doses of a meningococcal ACWY conjugate vaccine, while 8.0% of 1467 patients splenectomised after 2014 had received at least two doses of a serogroup B meningococcal vaccine. The VC for Hib was 18.7%. Nearly all splenectomised children under the age of 10 were vaccinated with Hib and PCV as these vaccines are included in the childhood immunisation program. For all vaccines, VC decreased with age. Twenty-nine invasive bacterial infections were registered post-splenectomy in 25 patients. Vaccination according to national recommendations could have prevented at least 8 (28%) of these infections. Our study showed that efforts are required to increase VC of splenectomised individuals in Norway.     

CD8 T cell memory development: CD4 T cell help is appreciated

An important goal of vaccination strategies is to elicit long term, effective immunity. Therefore it is imperative to define the parameters that regulate the development and preservation of the numbers and functional quality of cells that confer this property to the host. CD8 T cells are a key component of the host adaptive immune response that helps eradicate invading viruses and other cell-associated pathogens. Once the primary infection is controlled, the CD8 T cells transition from being effector cells into memory cells that act as sentinels of the immune system capable of rapidly purging the host of recurrent infections by the same pathogen. The factors that regulate and orchestrate this transition from effector CD8 T cells into functionally robust memory CD8 T cells are poorly understood. In recent years it has been determined that CD4 T cells play a vital role in the survival and functional responsiveness of memory CD8 T cells. However, the mechanism(s) of this interaction are still unclear.     

Relationship between patient copayments in Medicare Part D and vaccination claim status for herpes zoster and tetanus-diphtheria-acellular pertussis

Objective: To assess the relationship between copay amount and vaccination claim submission status for tetanus-diphtheria-acellular pertussis (Tdap) and herpes zoster (GSK study identifier: HO-14-14319).

Methods: Retrospective analyses were performed using vaccination administrative claims data in patients aged ≥65 years with ≥1 claim for Tdap or zoster vaccines between 2012 and 2014. To avoid confounding by other financial responsibility, analyses were conducted among patients in the copayment phase of insurance. The impact of patient copay amount on vaccination claim status (“canceled” vs. “paid”) was evaluated by logistic regression separately for Tdap and zoster, adjusting for patient and provider characteristics.

Results: A total of 81,027 (39.2% with canceled claims) and 346,417 patients (56.8% with canceled claims) were included in the Tdap and zoster analyses, respectively. Mean (standard deviation) copay for canceled vs. paid claims was $37.2 (18.4) vs. $31.1 (20.1) for Tdap and $64.9 (36.9) vs. $53.5 (38.8) for zoster. The adjusted odds ratios (ORs) for a canceled Tdap vaccine claim, compared with Objective: To assess the relationship between copay amount and vaccination claim submission status for tetanus-diphtheria-acellular pertussis (Tdap) and herpes zoster (GSK study identifier: HO-14-14319).

Methods: Retrospective analyses were performed using vaccination administrative claims data in patients aged ≥65 years with ≥1 claim for Tdap or zoster vaccines between 2012 and 2014. To avoid confounding by other financial responsibility, analyses were conducted among patients in the copayment phase of insurance. The impact of patient copay amount on vaccination claim status (“canceled” vs. “paid”) was evaluated by logistic regression separately for Tdap and zoster, adjusting for patient and provider characteristics.

Results: A total of 81,027 (39.2% with canceled claims) and 346,417 patients (56.8% with canceled claims) were included in the Tdap and zoster analyses, respectively. Mean (standard deviation) copay for canceled vs. paid claims was $37.2 (18.4) vs. $31.1 (20.1) for Tdap and $64.9 (36.9) vs. $53.5 (38.8) for zoster. The adjusted odds ratios (ORs) for a canceled Tdap vaccine claim, compared with $0 copay, were 1.19 ($1–25 copay), 1.76 ($26–50 copay), 2.42 ($51–75 copay) and 2.40 ($76–100 copay), all p?<?.001. The adjusted ORs for a canceled zoster vaccine claim, compared with $0 copay, were 1.02 ($1–25), 1.39 ($26–50), 1.66 ($51–75), 2.07 ($76–100) and 2.71 (>$100), all p?<?.001 except for $1–25 (p?=?.172).

Conclusions: High patient copay is a barrier to Tdap and zoster vaccinations in Medicare Part D patients. Providing vaccines at low or no copay may improve vaccination rates in these adults.

GSK study identifier: HO-14-14319.