Evidence Accumulation Rate Moderates the Relationship between Enriched Environment Exposure and Age-Related Response Speed Declines.

Older adults exposed to enriched environments (EEs) maintain relatively higher levels of cognitive function, even in the face of compromised markers of brain health. Response speed (RS) is often used as a simple proxy to measure the preservation of global cognitive function in older adults. However, it is unknown which specific selection, decision, and/or motor processes provide the most specific indices of neurocognitive health. Here, using a simple decision task with electroencephalography (EEG), we found that the efficiency with which an individual accumulates sensory evidence was a critical determinant of the extent to which RS was preserved in older adults (63% female, 37% male). Moreover, the mitigating influence of EE on age-related RS declines was most pronounced when evidence accumulation rates were shallowest. These results suggest that the phenomenon of cognitive reserve, whereby high EE individuals can better tolerate suboptimal brain health to facilitate the preservation of cognitive function, is not just applicable to neuroanatomical indicators of brain aging but can be observed in markers of neurophysiology. Our results suggest that EEG metrics of evidence accumulation may index neurocognitive vulnerability of the aging brain.Significance Statement Response speed in older adults is closely linked with trajectories of cognitive aging. Here, by recording brain activity while individuals perform a simple computer task, we identify a neural metric that is a critical determinant of response speed. Older adults exposed to greater cognitive and social stimulation throughout a lifetime could maintain faster responding, even when this neural metric was impaired. This work suggests EEG is a useful technique for interrogating how a lifetime of stimulation benefits brain health in aging.

Topological defects in multi-layered swarming bacteria.

Topological defects, which are singular points in a director field, play a major role in shaping active systems. Here, we experimentally study topological defects and the flow patterns around them, that are formed during the highly rapid dynamics of swarming bacteria. The results are compared to the predictions of two-dimensional active nematics. We show that, even though some of the assumptions underlying the theory do not hold, the swarm dynamics is in agreement with two-dimensional nematic theory. In particular, we look into the multi-layered structure of the swarm, which is an important feature of real, natural colonies, and find a strong coupling between layers. Our results suggest that the defect-charge density is hyperuniform, i.e., that long range density-fluctuations are suppressed.

Mono- to Multilayer Transition in Growing Bacterial Colonies.

The transition from monolayers to multilayered structures in bacterial colonies is a fundamental step in biofilm development. Observed across different morphotypes and species, this transition is triggered within freely growing bacterial microcolonies comprising a few hundred cells. Using a combination of numerical simulations and analytical modeling, here we demonstrate that this transition originates from the competition between growth-induced in-plane active stresses and vertical restoring forces, due to the cell-substrate interactions. Using a simple chainlike colony of laterally confined cells, we show that the transition sets when individual cells become unstable to rotations; thus it is localized and mechanically deterministic. Asynchronous cell division renders the process stochastic, so that all the critical parameters that control the onset of the transition are continuously distributed random variables. Here we demonstrate that the occurrence of the first division in the colony can be approximated as a Poisson process in the limit of large cell numbers. This allows us to approximately calculate the probability distribution function of the position and time associated with the first extrusion. The rate of such a Poisson process can be identified as the order parameter of the transition, thus highlighting its mixed deterministic-stochastic nature.

Web App- and Text Message-Based Patient Education in Mohs Micrographic Surgery-A Randomized Controlled Trial.

BACKGROUND: Consent and wound care (WC) videos are used for education in Mohs micrographic surgery (MMS). Postoperative text messaging is poorly studied. OBJECTIVE: Develop and evaluate perioperative resources for MMS patients-video modules (DermPatientEd.com) and postoperative text messaging (DermTexts.com). MATERIALS AND METHODS: A study was conducted on 90 MMS patients. Patients were randomized 1:1:1:1 to videos with text messages, videos-only, text messages-only, or control. Primary outcomes included preoperative anxiety and knowledge of MMS and postoperative care. The secondary outcome included helpfulness/preference of interventions. RESULTS: Patients experienced a 19% reduction in anxiety as measured by a visual analog scale after the MMS video (p = .00062). There was no difference in knowledge after the WC video (p = .21498). Patients were more likely to report the WC video "very helpful" when compared with the pamphlet in understanding postoperative WC (p = .0016). Patients in text messaging groups were not more likely to report the service as "very helpful" when compared with the pamphlet (p = .3566), but preferred to receive WC instructions by text message for future visits (p = .0001). CONCLUSION: These resources proved helpful and effective in reducing preoperative anxiety. Patients prefer text message-based WC instructions over pamphlets after experiencing the service, but do not find them more helpful.

Role of projection in the control of bird flocks.

Swarming is a conspicuous behavioral trait observed in bird flocks, fish shoals, insect swarms, and mammal herds. It is thought to improve collective awareness and offer protection from predators. Many current models involve the hypothesis that information coordinating motion is exchanged among neighbors. We argue that such local interactions alone are insufficient to explain the organization of large flocks of birds and that the mechanism for the exchange of long-range information necessary to control their density remains unknown. We show that large flocks self-organize to the maximum density at which a typical individual still can see out of the flock in many directions. Such flocks are marginally opaque--an external observer also still can see a substantial fraction of sky through the flock. Although this seems intuitive, we show it need not be the case; flocks might easily be highly diffuse or entirely opaque. The emergence of marginal opacity strongly constrains how individuals interact with one another within large swarms. It also provides a mechanism for global interactions: an individual can respond to the projection of the flock that it sees. This provides for faster information transfer and hence rapid flock dynamics, another advantage over local models. From a behavioral perspective, it optimizes the information available to each bird while maintaining the protection of a dense, coherent flock.

Patient perceptions of text-messages, email, and video in dermatologic surgery patients.

INTRODUCTION: We developed dermatology patient education videos and a post-operative text message service that could be accessed universally via web based applications. A secondary outcome of the study was to assess patient opinions of text-messages, email, and video in the health care setting which is reported here. METHODS: An investigator-blinded, randomized, controlled intervention was evaluated in 90 nonmelanoma MMS patients at Wake Forest Baptist Dermatology. Patients were randomized 1:1:1:1 for exposure to: 1) videos with text messages, 2) videos only, 3) text messages-only, or 4) standard of care. Assessment measures were obtained by the use of REDCap survey questions during the follow up visit. RESULTS: 1) 67% would like to receive an email with information about the procedure beforehand 2) 98% of patients reported they would like other doctors to use educational videos as a form of patient education 3) 88% of our patients think it is appropriate for physicians to communicate to patients via text message in certain situations. CONCLUSION: Nearly all patients desired physicians to use text-messages and video in their practice and the majority of patients preferred to receive an email with information about their procedure beforehand.

Trends in Mohs surgery from 1995 to 2010: an analysis of nationally representative data.

BACKGROUND: In Mohs surgery, the histologic verification of tumor removal results in a lower rate of cancer recurrence compared with simple excision. Factors associated with the increased use of Mohs surgery are not well characterized. OBJECTIVE: To investigate trends in the utilization of Mohs surgery. METHODS AND MATERIALS: The authors performed a retrospective analysis of the National Ambulatory Medical Care Survey for patient visits associated with Mohs surgery from 1995 to 2010. The authors assessed percentage of skin cancers managed with Mohs surgery, the most common locations of skin cancer managed with Mohs surgery, and patient demographics associated with Mohs surgery. RESULTS: Although there was an upward trend in the use of Mohs surgery (p = .004), a low percentage of skin cancers (average of 10.0%) were managed with this technique. When the surgical location was specified, Mohs surgery was most commonly used for the head and neck region. Demographic groups receiving Mohs surgery at higher rates included African Americans (44.2%) and patients aged 75 to 84 years (12.4%). CONCLUSION: There has been an upward trend in the use of Mohs surgery, particularly in the head and neck region where tissue preservation is essential.

Incidence, risk factors, and preventative management of skin cancers in organ transplant recipients: a review of single- and multicenter retrospective studies from 2006 to 2010.

BACKGROUND: Organ transplant recipients (OTRs) taking immunosuppressants are at high risk of skin cancer, which is the most common malignant condition in OTRs, so dermatologic surveillance is important for OTRs. OBJECTIVES: To characterize the most common skin cancers arising from chronic immunosuppression in OTRs. METHODS: A PubMed search for retrospective single- and multicenter studies reporting skin cancer incidence from 2006 to 2010 was undertaken. Data regarding each study's immunosuppressive regimen, affected skin cancer cohort, and associated risk factors were extracted. RESULTS: Thirty-six articles that met our inclusion criteria reported incidences of nonmelanoma skin cancer (NMSC), Kaposi's sarcoma, melanoma, and Merkel cell carcinoma. NMSC was the most commonly reported cancer of all skin cancers after transplantation. Common risk factors were sex, age, sunlight exposure, and immunosuppressive agent-related (duration, type). CONCLUSION: Sun education programs and frequent screenings in organ transplant clinics have provided the best preventative strategies after transplantation, although the characteristics of the immunosuppressive regimen also play an important role. Thus, the adjuvant strategy of modifying immunosuppression may be effective when confronting severe transplant-associated skin cancer. Although the decision-making process for curbing levels of immunosuppression is difficult, further long-term, randomized controlled studies should assess the effect of using less immunosuppressant medication while preserving graft function.

Quantifying and characterizing adverse events in dermatologic surgery.

BACKGROUND: Although office-based dermatologic procedures are generally considered safe, there is a lack of prospective data on the rate of adverse events (AEs) associated with these procedures. OBJECTIVE: To determine the frequency of AEs after dermatologic surgery and to characterize the most commonly encountered AEs. METHODS: A web-based interface was designed to track AEs with the input of four dermatologic surgeons. Patient demographic and operative data were collected at the time of the dermatologic surgery procedure. AEs occurring at any time during the data collection period were logged according to an a priori categorization scheme. RESULTS: The AE rate was 2.0% in this series of 2,418 subjects undergoing dermatologic surgery from February 1 through December 14, 2010. The most commonly reported AEs were suspicion of infection (64%), postoperative hemorrhage (20%), and wound dehiscence (8%). Suspicion of infection was slightly less frequent in subjects who received prophylactic preoperative antibiotics (0.4%) than in those who did not (1.5%, p = .07). There were no serious AEs and no deaths. CONCLUSION: AEs are uncommon after office-based dermatologic surgery procedures. Preoperative antibiotics may further decrease the infection rate after dermatologic surgery, but the risks and benefits must be weighed given the already low AE rate.

Self-Assembly Dynamics of Reconfigurable Colloidal Molecules.

Colloidal molecules are designed to mimic their molecular analogues through their anisotropic shape and interactions. However, current experimental realizations are missing the structural flexibility present in real molecules thereby restricting their use as model systems. We overcome this limitation by assembling reconfigurable colloidal molecules from silica particles functionalized with mobile DNA linkers in high yields. We achieve this by steering the self-assembly pathway toward the formation of finite-sized clusters by employing high number ratios of particles functionalized with complementary DNA strands. The size ratio of the two species of particles provides control over the overall cluster size, i.e., the number of bound particles N, as well as the degree of reconfigurability. The bond flexibility provided by the mobile linkers allows the successful assembly of colloidal clusters with the geometrically expected maximum number of bound particles and shape. We quantitatively examine the self-assembly dynamics of these flexible colloidal molecules by a combination of experiments, agent-based simulations, and an analytical model. Our "flexible colloidal molecules" are exciting building blocks for investigating and exploiting the self-assembly of complex hierarchical structures, photonic crystals, and colloidal metamaterials.

Polymer vesicles with a colloidal armor of nanoparticles.

The fabrication of polymer vesicles with a colloidal armor made from a variety of nanoparticles is demonstrated. In addition, it is shown that the armored supracolloidal structure can be postmodified through film-formation of soft polymer latex particles on the surface of the polymersome, hereby effectively wrapping the polymersome in a plastic bag, as well as through formation of a hydrogel by disintegrating an assembled polymer latex made from poly(ethyl acrylate-co-methacrylic acid) upon increasing the pH. Furthermore, ordering and packing patterns are briefly addressed with the aid of Monte Carlo simulations, including patterns observed when polymersomes are exposed to a binary mixture of colloids of different size.

Confinement-induced self-organization in growing bacterial colonies.

We investigate the emergence of global alignment in colonies of dividing rod-shaped cells under confinement. Using molecular dynamics simulations and continuous modeling, we demonstrate that geometrical anisotropies in the confining environment give rise to an imbalance in the normal stresses, which, in turn, drives a collective rearrangement of the cells. This behavior crucially relies on the colony's solid-like mechanical response at short time scales and can be recovered within the framework of active hydrodynamics upon modeling bacterial colonies as growing viscoelastic gels characterized by Maxwell-like stress relaxation.

Anti-CD38 antibody-mediated clearance of human repopulating cells masks the heterogeneity of leukemia-initiating cells.

Immunodeficient mice are increasingly used to assay human hematopoietic repopulating cells as well as leukemia-initiating cells. One method commonly used to isolate these rare cells is to sort cells stained with fluorochrome-conjugated antibodies into fractions, then transplant the different fractions into immunodeficient mice to test their repopulating ability. The antibodies are generally treated as being neutral in terms of their effects on the experiment. Human repopulating cells are thought to express CD34 and lack CD38. Here we present evidence that anti-CD38 antibodies have a profound inhibitory effect on engraftment of cord blood and leukemia cells. We show that this effect is Fc-mediated and can be overcome by treating mice with immunosuppressive antibodies. When this inhibitory effect is prevented, we demonstrate that the CD34(+)CD38(+) fraction of certain acute myeloid leukemia samples contains all, or at least most, leukemia-initiating cell capacity. This study highlights the potential pitfall of antibody-mediated clearance of repopulating cells and is important for any groups working with this model. More importantly, the work suggests that there is greater variation in the phenotypes of leukemia-initiating cells than previously suggested.

Detecting adverse events in dermatologic surgery.

BACKGROUND: Despite increasing awareness of and public attention to patient safety, little is documented about how adverse events (AEs) can or should be monitored in dermatologic surgery. Data to address this shortcoming are needed, although well-defined methodologies have yet to be implemented. OBJECTIVE To summarize current strategies in detecting adverse outcomes of dermatologic surgical procedures. MATERIALS AND METHODS: A Medline literature search was conducted using the terms "adverse event,""detection,""reporting,""monitoring," and "surgery." Articles selected addressed the efficacy of one or more AE reporting techniques in surgical patients. RESULTS: Prospective and retrospective reporting methods were identified, with morbidity and mortality conference being the most commonly used method of AE reporting. Retrospective medical record review, the retrospective trigger tool approach, and an anonymous electronic reporting system were more sensitive approaches. The Surgical Quality Improvement Program, a program that has successfully translated AE data into lower postoperative morbidity and mortality, was analyzed. CONCLUSIONS: Although generally considered safe, dermatologic surgery has no current standard for AE reporting. Standard definitions and high-quality data regarding AEs" currently limit this analysis. Pilot studies are needed to develop feasible measures, with the goal of increasing the sensitivity of AE detection and ultimately improving patient outcomes.

Cooperative ordering of treadmilling filaments in cytoskeletal networks of FtsZ and its crosslinker ZapA.

During bacterial cell division, the tubulin-homolog FtsZ forms a ring-like structure at the center of the cell. This Z-ring not only organizes the division machinery, but treadmilling of FtsZ filaments was also found to play a key role in distributing proteins at the division site. What regulates the architecture, dynamics and stability of the Z-ring is currently unknown, but FtsZ-associated proteins are known to play an important role. Here, using an in vitro reconstitution approach, we studied how the well-conserved protein ZapA affects FtsZ treadmilling and filament organization into large-scale patterns. Using high-resolution fluorescence microscopy and quantitative image analysis, we found that ZapA cooperatively increases the spatial order of the filament network, but binds only transiently to FtsZ filaments and has no effect on filament length and treadmilling velocity. Together, our data provides a model for how FtsZ-associated proteins can increase the precision and stability of the bacterial cell division machinery in a switch-like manner.

Cost-effectiveness of biologic treatments for psoriasis based on subjective and objective efficacy measures assessed over a 12-week treatment period.

BACKGROUND: The cost-effectiveness of biologic agents is not well delineated. OBJECTIVE: To determine the cost-effectiveness of biologic agents in cost per patient achieving a minimally important difference in Dermatology Life Quality Index (DLQI MID) and cost per patient achieving a 75% improvement in Psoriasis Area Severity Index (PASI-75), assessed over a 12-week period. METHOD: Efficacies of the agents were determined through a literature review; treatment paradigms and associated costs were determined. The cost-effectiveness of the agents was determined and sensitivity analysis performed. RESULTS: Etanercept at a dose of 25 mg administered subcutaneously (SQ) once weekly was the most cost-effective agent in cost per patient achieving DLQI minimally important difference; infliximab at a dose of 3 mg/kg administered intravenously (IV) for 3 infusions, adalimumab at a dose of 40 mg SQ every other week, and etanercept at a dose of 25 mg SQ twice weekly were the next most cost-effective agents in cost per patient achieving the DLQI minimally important difference. Intravenous infliximab at a dose of 3 mg/kg was the most cost-effective agent in terms of cost per patient achieving PASI-75 improvement; intravenous infliximab at a dose of 5 mg/kg and adalimumab at a dose of 40 mg SQ every other week were the next most cost-effective agents in cost per patient achieving PASI-75 improvement. LIMITATIONS: This study had a limited time horizon of 12 weeks; generalizing the results to longer treatment periods may not be accurate and is not advisable. Additionally, when sensitivity analyses were performed, multiple agents had overlapping cost-effectiveness ratios at relatively low levels of variance; thus it may not be accurate to differentiate the cost-effectiveness of these agents. CONCLUSIONS: Different biologic agents for psoriasis appear to have different cost-effectiveness values; within the limitations of the available data, infliximab and adalimumab appear to be the most cost-effective agents.

Adherence to acitretin and home narrowband ultraviolet B phototherapy in patients with psoriasis.

BACKGROUND: In the treatment of psoriasis, patient adherence to oral medications is poor and even worse for topical therapy. However, few data exist about adherence rates to home phototherapy, adding to concerns about the appropriateness of home phototherapy as a psoriasis treatment option. OBJECTIVE: We sought to assess adherence to both oral acitretin and home ultraviolet B phototherapy for the treatment of psoriasis. METHODS: In all, 27 patients with moderate to severe psoriasis were treated with 10 to 25 mg of acitretin daily, combined with narrowband ultraviolet B, 3 times weekly at home, for 12 weeks. Adherence to acitretin was monitored by an electronic monitoring medication bottle cap, and to phototherapy by a light-sensing data logger. RESULTS: Adherence data were collected on 22 patients for acitretin and 16 patients for adherence to ultraviolet B. Mean adherence to acitretin decreased steadily during the 12-week trial (slope -0.24), whereas mean adherence to home phototherapy remained steady at 2 to 3 d/wk. Adherence was similar between patients who reported side effects and those who did not. LIMITATIONS: Small sample size and lack of follow-up on some patients were limitations of this study. CONCLUSIONS: Adherence rates to home phototherapy were very good and higher than adherence rates for the oral medication. Side effects of treatment were well tolerated in this small group and did not affect use of the treatment. Home phototherapy with acitretin may be an appropriate option for some patients with extensive psoriasis.

Open label trial of alefacept in palmoplantar pustular psoriasis.

BACKGROUND: Palmoplantar pustular psoriasis (PPP) is difficult to treat. We assessed the effectiveness of alefacept in PPP and the safety of a 30 mg/week dose. METHODS: Fifteen individuals with PPP were started on 15 mg/week intramuscularly (IM) alefacept. Efficacy was measured by the PPP severity instrument (PSI). Treatment was continued for 16 weeks, and the alefacept dose was increased to 30 mg/week IM at week 9 if the PSI did not decrease by at least 25%. Other outcomes included physician's global assessment (PGA), reported adverse events and CD4+ T-lymphocyte counts. Clinical response was observed for 12 weeks after the last injection. RESULTS: The severity of PPP improved in both the PSI and the PGA (p<0.0001 and p = 0.0009, respectively). Much of the improvement occurred after 10 weeks of therapy. Nail severity scores improved (p = 0.0003). CD4+ counts decreased, but all remained >250 cells/mm3. There were no severe adverse effects or discontinuations due to adverse events. CONCLUSIONS: Alefacept in doses up to 30 mg/week was well tolerated in patients with PPP and appeared to have some efficacy. The use of concomitant therapy, the lack of a comparator, and the small sample size are limitations of the study.

Imiquimod: a review of basal cell carcinoma treatments.

Basal cell carcinoma (BCC) is regarded as the most prevalent malignant skin tumor in whites. A variety of surgical and nonsurgical interventions are available to treat BCC. In recent years, an immune response modifier drug, imiquimod, has been approved in treating superficial BCC (sBCC). The objective of the authors was to review the published literature to evaluate outcomes such as efficacy, safety, and quality of life associated with imiquimod treatment among patients with sBCC. A MEDLINE search of the literature was performed to identify studies published between January 1, 1995 and March 31, 2008 that evaluated imiquimod efficacy, safety, and quality of life in treating BCC. Overall, imiquimod 5% cream was associated with increased clinical and histologic clearance among patients with sBCC as compared to placebo. The findings from short-term cost effectiveness studies suggest that use of imiquimod 5% cream can be more cost-effective than surgical interventions such as excision surgery among patients with superficial BCC. Future studies evaluating long term cost effectiveness of imiquimod treatment are warranted.