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The SARS-CoV-2 outbreak in 2020 evolved into a global pandemic, and COVID-19 vaccines became rapidly available, including for pediatric patients. However, questions emerged that challenged vaccine acceptance and use. We aimed to answer these questions and give recommendations applicable for use in pediatric patients with cancer by healthcare professionals and the public.A 12-member global COVID-19 Vaccine in Pediatric Oncology Working Group made up of physicians and nurses from all world regions met weekly from March to July 2021. We used a modified Delphi method to select the top questions. The Working Group, in four-member subgroups, answered assigned questions by providing brief recommendations, followed by a discussion of the rationale for each answer. All Working Group members voted on each recommendation using a scale of 1 to 10, 10 being complete agreement. A "pass" recommendation corresponded to an agreement ≥7.5.We selected 15 questions from 173 suggested questions. Based on existing published information, we generated answers for each question as recommendations. The overall average agreement for the 24 recommendations was 9.5 (95% CI 9.4-9.6).Top COVID-19 vaccine-related questions could be answered using available information. Reports on COVID-19 vaccination and related topics have been published at record speed, aided by available technology and the priority imposed by the pandemic; however, all efforts were made to incorporate emerging information throughout our project. Recommendations will be periodically updated on a dedicated website.

Recent designs have allowed hollow cathode gas plasma sources to be adopted for use in plasma-enhanced atomic layer deposition with the benefit of lower oxygen contamination for non-oxide films (a brief review of this is provided). From a design perspective, the cathode metal is of particular interest since—for a given set of conditions—the metal work function should determine the density of electron emission that drives the hollow cathode effect. However, we found that relatively rapid surface modification of the metal cathodes in the first hour or more of operation has a stronger influence. Langmuir probe measurements and hollow cathode electrical characteristics were used to study nitrogen and oxygen plasma surface modification of aluminum and stainless-steel hollow cathodes. It was found that the nitridation and oxidation of these metal cathodes resulted in higher plasma densities, in some cases by more than an order of magnitude, and a wider range of pressure operation. Moreover, it was initially thought that the use of aluminum cathodes would not be practical for gas plasma applications, as aluminum is extremely soft and susceptible to sputtering; however, it was found that oxide and nitride modification of the surface could protect the cathodes from such problems, possibly making them viable.

Cervical cancer adversely impacts African American communities. While disparities in incidence remain unclear, communities continue to use forums to increase cervical cancer education. The purpose of this paper is to examine the efficacy of using community forums to increase human papillomavirus vaccine (HPVV) and cervical cancer knowledge in African American communities. This study is a one-group pretest-posttest study design using a 17-item questionnaire to collect data from 412 participants in diverse communities. Our analyses revealed perceived knowledge increased significantly after the forums for African American participants. For African Americans, perceived knowledge prior to the forums was explained by gender, access to care, and trust in clinical trials. After the forum, perceived knowledge was associated with access to care and trust in vaccines. Participants who had health insurance reported higher perceived HPV and cervical cancer knowledge and greater trust in vaccines. This study found community forums that address the cultural and historical context of research mistreatment related to HPVV development and include diverse racial/ethnic representation of stakeholders may be a useful strategy to increase HPVV, and cervical cancer knowledge in African American communities.

Background Human papillomavirus (HPV)-associated subsequent malignant neoplasms (SMNHPV ) in childhood cancer survivors are poorly understood. Methods The cumulative risk of SMNHPV was assessed among 24,363 Childhood Cancer Survivor Study participants. Standardized incidence ratios (SIRs) and absolute excess risk were calculated using age-matched, sex-matched, and calendar year rates from the Surveillance, Epidemiology, and End Results program. Poisson regression models identified SMNHPV risk factors, evaluating relative SIRs (rSIR) and 95% confidence intervals (95% CIs). Results In total, 46 survivors developed an SMNHPV (median age, 31 years [range, 10-56 years]; median time from primary cancer, 21 years [range, 9-35 years]). SMNHPV sites included oropharynx (N = 44), anorectum (N = 6), uterine cervix (N = 2), and vulva (N = 2). The 33-year cumulative incidence was 0.3% (95% CI, 0.2%-0.4%), and the SIR was nearly 3-fold that of the general population (SIR, 2.86; 95% CI, 2.05-4.00). Female survivors were not at increased risk of cervical or vulvar cancers compared with the general population. All survivors had an elevated risk of oropharyngeal SMNHPV (males: SIR, 4.06; 95% CI, 2.37-6.97; females: SIR, 8.44; 95% CI 4.88-14.61) and anorectal SMNHPV (males: SIR, 13.56; 95% CI, 5.09-36.13; females: SIR, 9.15; 95% CI, 2.29-36.61). Males (vs females: rSIR, 1.99; 95% CI, 1.00-3.94); head, neck, and pelvic radiotherapy doses >3000 centigray (vs none: rSIR, 2.35; 95% CI, 1.11-4.97); and cisplatin-equivalent doses >400 mg/m2 (vs none: rSIR, 4.51; 95% CI, 1.78-11.43) were associated with increased SMNHPV SIRs in multivariable analysis. Conclusions Childhood cancer survivors are at increased risk for SMN in sites susceptible to HPV-associated malignancies. Further research examining HPV in the etiology of SMN and the promotion of HPV vaccination and surveillance guidelines for SMNHPV in cancer survivors is warranted.

Background The Infectious Diseases Society of America (IDSA) guidelines recommend collecting blood cultures for the first 3 days of febrile neutropenia (FN) in the clinically stable oncology patient with persistent fevers. Nonetheless, many physicians send daily blood cultures beyond 3 days, and the impact of that practice is uncertain. Procedure We reviewed pediatric FN episodes from July 2009 to May 2014 at University of Chicago Comer Children's Hospital. For each positive culture, we determined if it was a pathogen or a contaminant. We reviewed episode and patient demographics to identify risk factors for subsequent positive blood cultures in the setting of an initially negative culture. Results We identified 381 episodes of FN in 162 patients. Of those, 87 had a positive blood culture on day 1 (21.0% incidence of bacteremia). Of 294 episodes with a negative blood culture on day 1, six (2.04%, 95% confidence interval [CI] 0.42–3.67) had a positive culture after day 3. Of those, three were pathogens (1.02%, 95%CI –0.14 to 2.18), and only one was found in a hemodynamically stable patient (0.34%, 95%CI –0.33 to 1.01) with new mucositis. In the other two patients, Escherichia coli was isolated from blood cultures after day 10 in the setting of significant hemodynamic changes. Risk factor analysis performed in stable patients yielded nonsignificant results. Conclusions Of 294 FN episodes with an initial negative blood culture, only one episode of bacteremia occurred without hemodynamic changes past day 3, supporting the IDSA guidelines to discontinue blood cultures in stable FN patients after day 3.

For stationary first passage percolation in two dimensions, the existence and uniqueness of semi-infinite geodesics directed in particular directions or sectors has been considered by Damron and Hanson (Commun. Math. Phys., 2014), Ahlberg and Hoffman (preprint, 2016), and others. However the main results do not cover geodesics in the direction of corners of the limit shape $\mathcal{B}$, where two facets meet. We construct an example with the following properties: (i) the limiting shape is an octagon, (ii) semi-infinite geodesics exist only in the four axis directions, and (iii) in each axis direction there are multiple such geodesics. Consequently, the set of points of $\partial \mathcal{B}$ which are in the direction of some geodesic does not have all of $\mathcal{B}$ as its convex hull., 26 pages, 4 figures

Neuroblastoma is the second most common childhood tumor. Survival is poor even with intensive therapy. In a search for therapies to neuroblastoma, we assessed the oncolytic potential of Zika virus. Zika virus is an emerging mosquito-borne pathogen unique among flaviviruses because of its association with congenital defects. Recent studies have shown that neuronal progenitor cells are likely the human target of Zika virus. Neuroblastoma has been shown to be responsive to infection. In this study, we show that neuroblastoma cells are widely permissive to Zika infection, revealing extensive cytopathic effects (CPE) and producing high titers of virus. However, a single cell line appeared poorly responsive to infection, producing undetectable levels of non-structural protein 1 (NS1), limited CPE, and low virus titers. A comparison of these poorly permissive cells to highly permissive neuroblastoma cells revealed a dramatic loss in the expression of the cell surface glycoprotein CD24 in poorly permissive cells. Complementation of CD24 expression in these cells led to the production of detectable levels of NS1 expression after infection with Zika, as well as dramatic increases in viral titers and CPE. Complementary studies using the Zika virus index strain and a north African isolate confirmed these phenotypes. These results suggest a possible role for CD24 in host cell specificity by Zika virus and offer a potential therapeutic target for its treatment. In addition, Zika viral therapy can serve as an adjunctive treatment for neuroblastoma by targeting tumor cells that can lead to recurrent disease and treatment failure.

We set out to assess the feasibility and uptake of an on-site influenza vaccination campaign targeting taxi drivers in airport taxicab lots in Chicago, Illinois. Influenza vaccine was provided by the Chicago Department of Public Health as this event aligned with ongoing efforts to provide influenza vaccinations throughout the city. Clinicians and clinic support staff were volunteers recruited from the University of Chicago Medicine and incorporated nursing staff, physicians, physician residents, and administrative support. Together, this allowed for a cost-effective approach to provide free influenza vaccines to the primarily uninsured taxi driver population. During these events, 545 taxi drivers received influenza vaccine in 2012 while 354 drivers were immunized in 2013. Nearly all drivers reported uninsured or under-insured status. The ability to use volunteers and healthcare organization's desires to meet the needs of the community, in collaboration with often under-staffed but highly dedicated local health departments have the potential to offer valuable public health services to underserved members of the community. Educational initiatives targeting vaccine hesitancy and misinformation may be necessary to improve immunization coverage among this population.

Antipsychotics are a class of psychiatric medication that is primarily effective at reducing psychosis symptoms, particularly in schizophrenia and bipolar disorders. This study aims to formulate mixtures of the antipsychotic drugs quetiapine fumarate (QUE), nortriptyline (NOR), propranolol (PROP) and haloperidol (HAL) with excipients urea, niacin (NIA) and niacinamide (NIM) to obtain an enhanced bioavailability and therapeutic effect. The mixtures were prepared by the solvent method and are characterized by various analytical techniques such as differential scanning calorimetry, wide angle X-ray diffraction, scanning electron microscopy and dissolution studies. Out of the various mixtures that have been prepared and tested, five of them showed eutectic behavior and their eutectic points are as follows: quetiapine fumarate–urea (QUE–UREA) 20–80, w/w; nortriptyline–niacin (NOR–NIA) 70–30, w/w; propranolol–niacin (PROP–NIA) 80–20, w/w; propranolol–niacinamide (PROP–NIM) 40–60, w/w; and haloperidol–niacinamide (HAL–NIM) 20–80, w/w. DSC investigation has revealed the formation of an eutectic system and the phase diagrams and Tamman’s triangle construction along with the hot-stage microscopy confirmed their melting points. PXRD study indicated no chemical interaction between either of the mixtures, while SEM study showed the size reduction in these mixtures that has been achieved. In vitro studies of the five mixtures showed an appreciable increase in the dissolution rate compared to that of the drug alone. In conclusion, five simple eutectic mixtures have been formulated by the solvent method and were found to show better dissolution rates than that of the pure form of the drugs, thus improving the bioavailability of these poorly water-soluble drugs.

This project aims to study the nature of interaction and orientation of selected drugs such as dexamethorphan HBr (DXM), diphenhydramine HCl (DPH), and lidocaine HCl (LDC) inclusion complexes with hydroxyl-propyl s-cyclodextrin (HP-s-CD) using 1HNMR spectroscopy, 2D-NMR ROESY and molecular-modeling techniques. Freeze-drying technique was used to formulate the inclusion complexes between DXM, DPH and LDC with HP-s-CD (1:1 M ratio) in solid state. Inclusion complex formation was initially characterized by Fourier transform-infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), X-ray diffraction (XRD) and scanning electron microscopy (SEM) techniques. Further characterization of inclusion complexes to determine the interaction of DXM, DPH and LDC with HP-β-CD was performed using the 1HNMR spectroscopy, 2D-NMR ROESY and molecular modeling techniques. Inclusion complexes of DXM, DPH and LDC with HP-s-CD were successfully prepared using the freeze-drying technique. Preliminary studies with FT-IR, DSC, XRD and SEM indicated the formation of inclusion complexes of DXM, DPH and LDC with HP-β-CD at 1:1 M ratio. 1HNMR study showed a change in proton chemical shift upon complexation. 2D-NMR ROESY (two-dimensional) spectroscopy gave an insight into the spatial arrangement between the host and guest atoms. 2D-ROESY experiments further predicted the direction of orientation of guest molecules, indicating the probability that amino moieties of DXM, DPH and LDC are inside the hydrophobic HP-s-CD cavity. Cross-peaks of inclusion complexes demonstrated intermolecular nuclear Overhauser effects (NOE) between the amino protons in DXM, DPH and LDC and H-atoms of HP-s-CD. Molecular modeling studies further confirmed the NMR data, providing a structural basis of the individual complex formations. Microsecond time-level molecular dynamics and metadynamics simulations indicate much stronger binding of DXM to HP-s-CD and more dynamic behavior for DPH and LDC. In particular, LDC can exhibit multiple binding modes, and even spent some time (∼1-2%) out of the carrier, proving the dynamic nature of the complex. To conclude, 2D-NMR and molecular dynamic simulations elucidate the formation of inclusion complexes and intermolecular interactions of DXM, DPH and LDC with HP-s-CD.

The availability of suppositories in Hungary, especially in clinical pharmacy practice, is usually provided by extemporaneous preparations. Due to the known advantages of rectal drug administration, its benefits are frequently utilized in pediatrics. However, errors during the extemporaneous manufacturing process can lead to non-homogenous drug distribution within the dosage units. To determine the root cause of these errors and provide corrective actions, we studied suppository samples prepared with exactly known errors using both cerimetric titration and HPLC technique. Our results show that the most frequent technological error occurs when the pharmacist fails to use the correct displacement factor in the calculations which could lead to a 4.6% increase/decrease in the assay in individual dosage units. The second most important source of error can occur when the molding excess is calculated solely for the suppository base. This can further dilute the final suppository drug concentration causing the assay to be as low as 80%. As a conclusion we emphasize that the application of predetermined displacement factors in calculations for the formulation of suppositories is highly important, which enables the pharmacist to produce a final product containing exactly the determined dose of an active substance despite the different densities of the components.

A union encounters forces which are of sufficient strength to override pressures to negotiate comparable settlements. To gain further insight into the nature of these forces and the union's reaction, the author interviewed union officials of the UAW in Detroit and made a study of 140 collective agreements carried on through the UAW in various industries in the same area., L'étude des conventions de travail signées par les représentants de UAW dans la région de Détroit permet de les classifier en deux catégories: celles des entreprises situées à l'intérieur de l'industrie de l'automobile et celles des entreprises situées à l'extérieur de cette industrie. Les facteurs qui expliquent l'écart dans les avantages obtenus dans la deuxième catégorie par rapport à la première sont les suivants:Tous ces facteurs jouent à des degrés différents dans la négociation de chacun des contrats. Et si l'on veut connaître les raisons pour lesquelles des contrats transiges par une même union s'écartent les uns des autres, il est nécessaire de jeter davantage de lumière sur chacun de ces facteurs.

We have observed unique variations in AC electrical conductivity of solids when studied with respect to temperature, time, and frequency. A wide range of solids were examined for this study e.g., organics, polymers, carbohydrates, active pharmacy ingredients (APIs), and amino acids. The observed dielectric analysis conductivity for this great number of organic materials follows an Arrhenius plot of log polar ionic conductivity which is linearly related to reciprocal temperature and the correlation of coefficient is 0.992–0.999. These experimental observations support the polaron hopping conduction model. Experimental results clearly show novel dielectric behavior of a linear increase in a log ionic conductivity versus temperature in the pre-melt/solid-state transition regions. We have differentiated the solids which show the conductivity variations in pre-melt from those which do not. Isothermal dielectric analysis was used to study the cause of this variation in solids which yielded the measure of behavior, i.e., the polarization time property. We have also studied the effect of various experimental factors (e.g., moisture and purity) on the results. Correlating dielectric with calorimetric analyses gave us a better understanding of solid-state properties. Calorimetric analysis was used to assure that the observed variations in the solid-state properties are not due to moisture or impurities present in the sample. The ASTM E698 “purity method” was employed to verify the purity of the chemicals. Activation energies were calculated based on Arrhenius behavior to better interpret the solid-state properties. As the different chemicals were heat–cool cycled they were more amorphous, as evidenced by the decreasing activation energy for charge transfer with an increasing amorphous content.

Prophylactic human papillomavirus (HPV) vaccines and new HPV screening tests, combined with traditional Pap test screening, provide an unprecedented opportunity to greatly reduce cervical cancer in the USA. Despite these advances, thousands of women continue to be diagnosed with and die of this highly preventable disease each year. This paper describes the initiatives and recommendations of national cervical cancer experts toward preventing and possibly eliminating this disease.In May 2011, Cervical Cancer-Free America, a national initiative, convened a cervical cancer summit in Washington, DC. Over 120 experts from the public and private sector met to develop a national agenda for reducing cervical cancer morbidity and mortality in the USA.Summit participants evaluated four broad challenges to reducing cervical cancer: (1) low use of HPV vaccines, (2) low use of cervical cancer screening, (3) screening errors, and (4) lack of continuity of care for women diagnosed with cervical cancer. The summit offered 12 concrete recommendations to guide future national and local efforts toward this goal.Cervical cancer incidence and mortality can be greatly reduced by better deploying existing methods and systems. The challenge lies in ensuring that the array of available prevention options are accessible and utilized by all age-appropriate women-particularly minority and underserved women who are disproportionately affected by this disease. The consensus was that cervical cancer can be greatly reduced and that prevention efforts can lead the way towards a dramatic reduction in this preventable disease in our country.

At certain temporal frequencies, the human cone flicker electroretinogram (ERG) contains multiple additional responses following the termination of a flicker train. The purpose of this study was to determine whether these poststimulus responses are a continuing response to the terminated flicker train or represent the oscillation of a resonant system. ERGs were recorded from 10 visually normal adults in response to full-field sinusoidally modulated flicker trains presented against a short-wavelength rod-saturating adapting field. The amplitude and timing properties of the poststimulus responses were evaluated within the context of a model of a second-order resonant system. At stimulus frequencies between 41.7 and 71.4 Hz, the majority of subjects showed at least three additional ERG responses following the termination of the flicker train. The interval between the poststimulus responses was approximately constant across stimulus frequency, with a mean of 14.4 ms, corresponding to a frequency of 69.4 Hz. The amplitude and timing characteristics of the poststimulus ERG responses were well described by an underdamped second-order system with a resonance frequency of 70.3 Hz. The observed poststimulus ERG responses may represent resonant oscillations of retinal ON bipolar cells, as has been proposed for electrophysiological recordings of poststimulus responses from retinal ganglion cells. However, further investigation is required to determine the types of retinal neurons involved in the generation of the poststimulus responses of the human flicker ERG.

summary Background: Oral cavity and in particular oral tongue cancers occur with a rising incidence in younger patients often lacking the typical risk factors of tobacco use, alcohol use, and human papilloma virus (HPV) infection. Their prognosis when treated with chemoradiation has not been well studied and responsible risk factors remain elusive. A viral etiology (other than HPV) has been hypothesized. Methods: First we analyzed outcomes from 748 head and neck cancer patients with locoregionally advanced stage tumors treated with curative-intent chemoradiation by anatomic site. Second, we analyzed seven oral tongue (OT) tumors from young, non-smokers/non-drinkers for the presence of viral mRNA using short-read massively-parallel sequencing (RNA-Seq) in combination with a newly-developed digital subtraction method followed by viral screening and discovery algorithms. For positive controls we used an HPV16-positive HNC cell line, a cervical cancer, and an EBV-LMP2A transgene lymphoma. Results: Younger patients with oral cavity tumors had worse outcomes compared to non-oral cavity patients. Surprisingly none of the seven oral tongue cancers showed significant presence of viral transcripts. In positive controls the expected viral material was identified. Conclusion: Oral cavity tumors in younger patients have a poor prognosis and do not appear to be caused by a transcriptionally active oncovirus.

Sepsis is a common and potentially devastating occurrence in NICUs. Sepsis is defined as the constellation of findings making up the systemic inflammatory response syndrome plus an infection. Newer studies now suggest that treatment of infants who have nonspecific signs of illness with prolonged antibiotics can lead to serious complications. The complexities of practicing medicine in the NICU sometimes limit our ability to secure a diagnosis of culture proven sepsis. The administration of antibiotics until bacterial infection can be reasonably ruled out should occur concurrently with evaluations of other plausible noninfectious diagnoses.

Coagulase negative staphylococci are increasingly common organisms isolated in the evaluation of neonates with sepsis. However, there is a lack of consensus on the definition of true infection and the criteria for treatment. This article presents clinically useful methods to distinguish true infection from contamination. Additionally, we describe clinically relevant virulence factors contributing to the pathogenicity of various species. Knowing these virulence factors may help to stratify patient risk for serious infection. There are inconsistent data regarding the clinical importance of coagulase negative staphylococcal infections in the neonatal population. This inconsistency highlights the importance of establishing a consensus for the diagnosis and treatment of these infections in both the clinical and research arenas.

Background. Many adolescents underutilize preventive services and are underimmunized. Methods. To promote medical homes and increase immunization rates, we conceptualized and implemented a 3-year, 8-school pilot school-located vaccination collaborative program. We sought community, parent, and school nurse input the year prior to implementation. We selected schools with predominantly Medicaid-enrolled or Medicaid-eligible students to receive Vaccines For Children stock vaccines. Nurses employed by a mass immunizer delivered these vaccines at participating schools 3 times a year. Results. Over 3 years, we delivered approximately 1800 vaccines at schools. School administrators, health centers, and neighboring private physicians generally welcomed the program. Parents did not express overt concerns about school-located vaccination. School nurses were not able to participate because of multiple school assignments. Obtaining parental consent via backpack mail was an inefficient process, and classroom incentives did not increase consent form return rate. The influenza vaccine had the most prolific uptake. The optimal time for administering vaccines was during regular school hours. Conclusions. Although school-located vaccination for adolescents is feasible, this is a paradigm shift for community members and thus accompanies challenges in implementation. High principal or school personnel turnover led to a consequent lack of institutional memory. It was difficult to communicate directly with parents. Because we were uncertain about the proportion of parents who received consent forms, we are exploring Internet-based and back-to-school registration options for making the consent form distribution and return process more rigorous. Securing an immunization champion at each school helped the immunization processes. Identifying a financially sustainable school-located vaccination model is critical for national expansion of school-located vaccination.

Adaptation refers to the ability of the visual system to adjust to the prevailing conditions of light stimulation in order to maximize sensitivity, reduce the effect of noise, and prevent neural overload or saturation. Many forms of visual adaptation have been identified, occurring at multiple sites within the visual pathway. The types of adaptation that are thought to be retinal in origin are light adaptation, contrast adaptation, chromatic adaptation, and dark adaptation. This article discusses the characteristics of these forms of adaptation and briefly describes the retinal processes that are presumed to underlie them.

To document a novel NYX gene mutation in a patient with X-linked complete congenital stationary night blindness and to describe this patient's electroretinogram (ERG) characteristics.ERGs were recorded from a 17-year-old male with a previously unreported NYX mutation (819GA) that results in a missense codon change (Trp237Ter). ERGs were recorded in response to brief-flash stimuli, 6.33-Hz sawtooth flicker, and sinusoidal flicker ranging from 6.33-100 Hz. The omitted stimulus response (OSR) of the flicker ERG, which is thought to be generated within the ON-pathway, was also assessed.The patient's single-flash responses were consistent with previously documented NYX ERG characteristics, including a high-luminance flash response that was electronegative under dark-adapted conditions and a square-like a-wave followed by an abnormally shaped positive potential under light-adapted conditions, both of which are consistent with an ON-pathway deficit. Further evidence for an ON-pathway deficit included: (1) ERGs to rapid-on sawtooth flicker in which b-wave amplitude was reduced more than a-wave amplitude, and (2) responses to sinusoidal flicker that lacked the normal amplitude minimum and phase inflection near 12 Hz, ERG characteristics that are like those of patients with other NYX mutations. Novel findings included a pronounced amplitude attenuation for sinusoidal flicker at frequencies above approximately 50 Hz and an absent OSR, suggesting ON-pathway dysfunction at high frequencies.The substantial loss of ERG amplitude and apparent ON-pathway dysfunction at high temporal frequencies distinguish this patient with a Trp237Ter NYX mutation from those with other previously reported NYX mutations.

One of the most divisive issues in pediatrics today concerns the proper response by pediatricians to parents who refuse routine childhood immunizations for their children. Many pediatricians refuse to care for such families. Others continue to provide care and continue to try to convince parents that the benefits of immunizations far outweigh the risks. Two of the most powerful arguments in favor of dismissing such parents are as follows: (1) their refusal suggests such lack of trust in the physicians’ recommendations that it undermines the basis for a meaningful physician–patient–parent relationship; and (2) unimmunized children present an unacceptable risk to other children in the physicians’ waiting rooms. This article examines those arguments.

Background. Skin infections occur commonly and often present therapeutic challenges to practitioners due to the growing concerns regarding multidrug-resistant bacterial, viral, and fungal strains. The antimicrobial properties of zinc sulfate and copper sulfate are well known and have been investigated for many years. However, the synergistic activity between these two metal ions as antimicrobial ingredients has not been evaluated in topical formulations. Objective. The aims of the present study were to (1) formulate topical creams and gels containing zinc and copper alone or in combination and (2) evaluate the in vitro antibacterial activity of these metal ions in the formulations. Method. Formulation of the gels and creams was followed by evaluating their organoleptic characteristics, physicochemical properties, and in vitro antibacterial activity against Escherichia coli and Staphylococcus aureus. Results. Zinc sulfate and copper sulfate had a strong synergistic antibacterial activity in the creams and gels. The minimum effective concentration was found to be 3 w/w% for both active ingredients against the two tested microorganisms. Conclusions. This study evaluated and confirmed the synergistic in vitro antibacterial effect of copper sulfate and zinc sulfate in a cream and two gels.

Organogels have emerged as an alternative carrier for small and macromolecules via transdermal, oral, rectal and ophthalmic routes. Pluronic lecithin organogels (PLO gels) are lecithin-based organogels widely used in compounding pharmacies as a vehicle for enhancing the transdermal permeability of many therapeutic drugs. However, the scientific and systematic evidence in support of how well PLO gels help in transdermal delivery is scanty. Recently, some clinical studies have reported nearly complete lack of bioavailability of certain topically administered drugs from PLO gels. The present review aims at summarizing gels and organogels, with a focus on the use of PLO gels in transdermal drug delivery. A special emphasis is placed on controversies looming over the use of PLO gels as a delivery platform for drugs via transdermal route. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

We study the intersection of two independent renewal processes, $\rho=\tau\cap\sigma$. Assuming that $\mathbf{P}(\tau_1 = n ) = \varphi(n)\, n^{-(1+\alpha)}$ and $\mathbf{P}(\sigma_1 = n ) = \tilde\varphi(n)\, n^{-(1+ \tilde\alpha)} $ for some $\alpha,\tilde \alpha \geq 0$ and some slowly varying $\varphi,\tilde\varphi$, we give the asymptotic behavior first of $\mathbf{P}(\rho_1>n)$ (which is straightforward except in the case of $\min(\alpha,\tilde\alpha)=1$) and then of $\mathbf{P}(\rho_1=n)$. The result may be viewed as a kind of reverse renewal theorem, as we determine probabilities $\mathbf{P}(\rho_1=n)$ while knowing asymptotically the renewal mass function $\mathbf{P}(n\in\rho)=\mathbf{P}(n\in\tau)\mathbf{P}(n\in\sigma)$. Our results can be used to bound coupling-related quantities, specifically the increments $|\mathbf{P}(n\in\tau)-\mathbf{P}(n-1\in\tau)|$ of the renewal mass function., Comment: 1 figure, 21 pages

Purpose The objective of this study was to identify motivations and barriers to HPV vaccination and culturally relevant and meaningful opportunities for vaccine promotion among African American mothers and adolescent daughters. Qualitative methods were employed to identify barriers to HPV immunization and understand mothers motivations to vaccinate their daughters. We conducted in-depth interviews with 19 mother–daughter pairs focused on 5 key areas: health history, prior vaccine experience, knowledge of HPV and HPV vaccine, relationship with physician, and experience of cervical dysplasia and cervical cancer (CD/CC). Results Four key factors drive HPV immunization among African-American mothers of adolescent daughters. First, mothers’ CD/CC disease experiences motivated a strong commitment to protect daughters from the trauma of CD/CC. Second, limited understanding of HPV and its connection to CD/CC made it difficult for mothers to assess the risk of infection or explain the medical benefits of the vaccine to their daughters. Third, mothers anticipate the sexual debut of adolescent daughters and advocate for healthcare interventions to protect them. Mothers were not deterred by multiple visits to complete the vaccine series; they likened HPV immunization to injectable contraceptives that require a series of injections and offer protection from the unintended consequences of sexual activity. Finally, mothers trusted physicians to initiate discussion of HPV immunization. Physicians who failed to initiate discussion and offer unconditional endorsement generated doubt about the vaccine among mothers and missed opportunities for immunization. Conclusions Our initial results indicate that physicians can engage in culturally relevant vaccine promotion in urban, underserved African American communities by initiating discussions of HPV immunization that (1) acknowledge mothers’ own CD/CC experiences, (2) support parenting strategies that aim to protect daughters from the unintended consequences of sexual activity, and (3) make explicit the connection between CD/CC and HPV infection, and between prevention of HPV infection and HPV immunization.

Late onset sepsis infections contribute a significant proportion of the morbidity and mortality of hospitalized infants, especially in very low birth weight infants. Although it is fairly clear which infants are at higher risk of developing sepsis, it is less clear whether a standard for diagnostic evaluation exists and is being used consistently across institutions. In the current setting of changing epidemiology and emergence of antibiotic-resistant organisms, it is important to evaluate the antimicrobial agents used for empirical therapy and to emphasize the importance of antimicrobial stewardship. In addition, it is imperative to evaluate possible methods for prevention of these infections.

Early onset sepsis in the newborn infant continues to be an important clinical problem for neonatologists everywhere in the world. Different routes of transmission, changes in causative agents, and potential antibiotic resistance all influence the choice of antibiotic therapy. Group B Streptococcus and Escherichia coli continue to be the major pathogens dictating antibiotic therapy in the United States. Ampicillin and gentamicin are the antibiotics used by most for empirical therapy; cephalosporins are used in certain clinical situations. In this review, we address the reasons for these choices while highlighting clinically relevant aspects of the antibiotics commonly used in the treatment of early onset sepsis in the newborn.

Although sepsis is one of the important etiologies of illness in hospitalized infants, it is often difficult to determine if an infant is truly infected and, moreover, how to treat these infections. To address the first issue, researchers have begun to examine techniques to shorten the amount of time it takes to culture and identify organisms. On the clinical side, the development of biomarkers may help physicians to better identify infants who are likely ill from infection versus those infants who are unstable from other processes. The ability to distinguish between these cohorts will help to curtail excessive use of empirical antibiotics. Even if infants are determined to truly have infection on the basis of a positive culture, it is becoming more challenging to appropriately treat causative organisms, as multidrug resistance becomes more prevalent. Furthermore, it becomes more important to evaluate strategies to prevent these infections before they occur.

Morphological and thermodynamic transitions in drugs as well as their amorphous and crystalline content in the solid state have been distinguished by thermal analytical techniques, which include dielectric analysis (DEA), differential scanning calorimetry (DSC), and macro-photomicrography. These techniques were used successfully to establish a structure versus property relationship with the United States Pharmacopeia standard set of active pharmaceutical ingredient (API) drugs. A distinguishing method is the DSC determination of the amorphous and crystalline content which is based on the fusion properties of the specific drug and its recrystallization. The DSC technique to determine the crystalline and amorphous content is based on a series of heat and cool cycles to evaluate the drugs ability to recrystallize. To enhance the amorphous portion, the API is heated above its melting temperature and cooled with liquid nitrogen to −120 °C (153 K). Alternatively a sample is program heated and cooled by DSC at a rate of 10 °C min−1. DEA measures the crystalline solid and amorphous liquid API electrical ionic conductivity. The DEA ionic conductivity is repeatable and differentiates the solid crystalline drug with a low conductivity level (10−2 pS cm−1) and a high conductivity level associated with the amorphous liquid (106 pS cm−1). The DSC sets the analytical transition temperature range from melting to recrystallization. However, analysis of the DEA ionic conductivity cycle establishes the quantitative amorphous and crystalline content in the solid state at frequencies of 0.10–1.00 Hz and to greater than 30 °C below the melting transition as the peak melting temperature. This describes the “activation energy method.” An Arrhenius plot, log ionic conductivity versus reciprocal temperature (K−1), of the pre-melt DEA transition yields frequency dependent activation energy (E a, J mol−1) for the complex charging in the solid state. The amorphous content is inversely proportional to the E a where the E a for the crystalline form is higher and lower for the amorphous form with a standard deviation of ±2%. There was a good agreement between the DSC crystalline melting, recrystallization, and the solid state DEA conductivity method with relevant microscopic evaluation. An alternate technique to determine amorphous and crystalline content has been established for the drugs of interest based on an obvious amorphous and crystalline state identified by macro-photomicrography and compared to the conductivity variations. This second “empirical method” correlates well with the “activation energy” method.

PURPOSE To determine the relative contributions of optical and non-optical sources of intrinsic blur to variations in visual acuity (VA) among normally sighted subjects. METHODS Best-corrected VA of 16 normally sighted subjects was measured using briefly presented (59 ms) tumbling E optotypes that were either unblurred or blurred through convolution with Gaussian functions of different widths. A standard model of intrinsic blur was used to estimate each subject's equivalent intrinsic blur (σint) and VA for the unblurred tumbling E (MAR0). For 14 subjects, a radially averaged optical point spread function due to higher-order aberrations was derived by Shack-Hartmann aberrometry and fit with a Gaussian function. The standard deviation of the best-fit Gaussian function defined optical blur (σopt). An index of non-optical blur (η) was defined as 1 - σopt/σint. A control experiment was conducted on five subjects to evaluate the effect of stimulus duration on MAR0 and σint. RESULTS.: The logarithm of the minimum angle of resolution (logMAR₀) for the briefly presented E was correlated significantly with log σint (r = 0.95, p < 0.01), consistent with previous work. However, logMAR₀ was not correlated significantly with log σopt (r = 0.46, p = 0.11). For subjects with logMAR₀ equivalent to ~20/20 or better, logMAR₀ was independent of log η, whereas for subjects with larger logMAR₀ values, logMAR₀ was proportional to log η. The control experiment showed a statistically significant effect of stimulus duration on logMAR₀ (p < 0.01) but a non-significant effect on σint (p = 0.13). CONCLUSIONS The relative contributions of optical and non-optical blur to VA varied among the subjects and were related to the subject's VA. Evaluating optical and non-optical blur may be useful for predicting changes in VA following procedures that improve the optics of the eye in patients with both optical and non-optical sources of VA loss.

The current United States Pharmacopeia (USP) test for the disintegration of drug tablets does not measure initial disintegration times and does not adequately describe tablet disintegration mechanisms. An Isothermal Mechanical Analysis (IsoTMA) method meeting USP specifications has been developed to measure the initial time and rate of drug disintegration. TMA monitors the physical dimension of the formulated drug tablet as a function of time, temperature, applied stress, and pH. TMA can be used to measure the swelling, shrinkage, or disintegration of a formulated tablet in a specified fluid. The focus of this study is to validate an efficient and precise IsoTMA method to measure dimensional stability of solid dose tablets. The precision of the method along with the effect of pH (1–10) and temperature (25–37 °C) on the rate of delivery was determined for nine drugs. Graphical representations of dimensional changes over time were created and compared. Drug delivery in a specific liquid medium was measured by UV analysis for the active pharmaceutical ingredient. An increase in temperature decreased the disintegration time and increased the disintegration rate (mm/min). For the drugs that are studied in this article, pH did not have an appreciable effect on the rate of disintegration.

Novel dielectric behavior of a linear increase in ionic conductivity prior to melt temperature was observed for active pharmaceutical ingredients (APIs), organic chemicals, amino acids, and carbohydrates. Though, there are solids like polyolefins and long chain organic compounds (tetracosane, pentacosane) which do not exhibit this premelt behavior (i.e., the temperature where the onset of increase in ionic conductivity to melt temperature). We have discovered novel electrical conductivity properties and other physical analytical variations which can lead to unique synthetic routes of certain chemical entities. The above-mentioned unique variations are not related to solid–solid transitions which are quite often observed in pharmaceutical crystalline solids. These new properties are related to amorphous crystalline behavior of a solid. We have also studied the effect of various experimental variables: such as amount of mass tested, applied frequency at a given electric field and heating rate, which results in varying the onset temperature of the increase in ionic conductivity. Melting of the solids was correlated using differential scanning calorimetry (DSC). Activation energies for all the solids were measured in the premelt region using an Arrhenius plot at a specific frequency since we observed changes in the conductivity with frequency. This study focused on frequencies 0.1 to 10 Hz, since the conductivity at these frequencies related to surface analysis. This new physical properties are leading to new electro synthetic procedures to modify or prepare chemicals.

We study the solid-on-solid interface model above a horizontal wall in three dimensional space, with an attractive interaction when the interface is in contact with the wall, at low temperatures. There is no bulk external field. The system presents a sequence of layering transitions, whose levels increase with the temperature, before reaching the wetting transition., Comment: 61 pages, 6 figures. Miscellaneous corrections and changes, primarily in Section 4. Figure 5 added.

A female infant born at 36 weeks to a 25-year-old G2P2 mother by normal spontaneous vaginal delivery after an uncomplicated pregnancy, presents with respiratory distress and shock at 1 month of age. She has had 2 days of increased work of breathing with tachypnea and tracheal tugging; 2 weeks of cough, rhinorrhea, and nasal congestion; and currently an episode of cyanosis lasting 2 minutes. Weight gain has been appropriate since birth. On physical examination, rectal temperature is 34°C, heart rate is 126 beats per minute, blood pressure is 58/31 mm Hg, and oxygen saturation is 40% in room air. The patient has prolonged capillary refill indicative of poor peripheral perfusion, coarse breath sounds with rhonchi bilaterally, and hepatosplenomegaly. A chest radiograph shows diffuse coarse bilateral interstitial opacities with lucency over the right middle lobe (Fig 1). Figure 1. Chest radiograph demonstrating bilateral diffuse coarse interstitial markings with subsegmental left lower lobe opacity, right mid-lobe lucency, and small right-sided pleural effusion. Initial laboratory studies include an arterial blood gas with pH of 7.03, a Pco2 of 70 mm Hg, calculated bicarbonate of 18 mEq/L, and a base excess of –13; the patient’s serum lactate level was 6.7 mmol/L. The white blood cell count is 25.6 × 103/μL (25.6 × 109/L) with 41% neutrophils and 38% band forms. The C-reactive protein level is 107 mg/L. The serum total bilirubin is 1.3 mg/dL, alanine aminotransferase is 22 U/L, and aspartate aminotransferase is 88 U/L. Her prothrombin time (PT) is 31.9 seconds (international normalized ratio: 3.1), and activated partial thromboplastin time (aPTT) is 51.9 seconds. The cerebrospinal fluid cell count (CSF) cell count, differential, protein, and glucose are normal. Samples of blood, urine, CSF, and endotracheal tube aspirate were sent for viral and bacterial culture and polymerase chain reaction assays. Quantitative …