Development of a topical bacteriophage gel targeting Cutibacterium acnes for acne prone skin and results of a phase 1 cosmetic randomized clinical trial.

Background: Topical antibiotics are frequently used to treat acne vulgaris. Their prolonged use, often for longer durations than recommended, has led to antibiotic resistance in Cutibacterium acnes (C. acnes), a bacterium implicated in acne pathophysiology. Bacteriophage (phage), which specifically target C. acnes by a different mechanism of action and do not harm potentially beneficial bacteria, may offer an alternative approach for improvement of the appearance of acne prone skin. Objectives: To identify and characterize C. acnes targeting phage, carry out a comprehensive preclinical safety evaluation of phages selected for further development and examine their safety, tolerability and ability to target facial C. acnes when applied topically in a cosmetic clinical study including participants with mild-to-moderate acne. Methods: Phages were isolated by conventional microbiological methods also used to examine their breadth of host range on different C. acnes strains and specificity to this bacterial species. Safety assessment of three selected phages was carried out by complete genomic analysis to assure the absence of undesired sequences and by ex vivo models employed to evaluate the safety, irritability and potential systemic bioavailability of phage applied topically. A randomized, controlled clinical study assessed safety, tolerability and efficacy in targeting facial C. acnes. Results: Wide host range phages that also target antibiotic resistant C. acnes were identified. Their genomes were shown to be free of undesired genes. The three-phage cocktail, BX001, was not irritant to human skin or ocular tissues in ex vivo models and did not permeate through human epidermis. In a cosmetic clinical study, topically applied BX001 was safe and well tolerated and reduced the facial burden of C. acnes. Conclusions: Combined in silico and ex vivo approaches successfully predicted the observed safety and efficacy of C. acnes targeting phage when these were topically administered in a well-controlled cosmetic clinical study.

A new photolysis laser-induced fluorescence instrument for the detection of H2O and HDO in the lower stratosphere.

We present a new instrument, Hoxotope, for the in situ measurement of H(2)O and its heavy deuterium isotopologue (HDO) in the upper troposphere and lower stratosphere aboard the NASA WB-57. Sensitive measurements of deltaD are accomplished through the vacuum UV photolysis of water followed by laser-induced fluorescence detection of the resultant OH and OD photofragments. The photolysis laser-induced fluorescence technique can obtain S/N>20 for 1 ppbv HDO and S/N>30 for 5 ppmv H(2)O for 10 s data, providing the sensitivity required for deltaD measurements in the tropopause region. The technique responds rapidly to changing water concentrations due to its inherently small sampling volume, augmented by steps taken to minimize water uptake on instrument plumbing. Data from the summer 2005 Aura Validation Experiment Water Isotope Intercomparison Flights (AVE-WIIF) out of Houston, TX show agreement for H(2)O between Hoxotope and the Harvard water vapor instrument and for HDO between Hoxotope and the Harvard ICOS water isotope instrument, to within stated instrument uncertainties. The successful intercomparison validates Hoxotope as a credible source of deltaD data in the upper troposphere and lower stratosphere.

Quantifying stratospheric ozone in the upper troposphere with in situ measurements of HCl.

We have developed a chemical ionization mass spectrometry technique for precise in situ measurements of hydrochloric acid (HCl) from a high-altitude aircraft. In measurements at subtropical latitudes, minimum HCl values found in the upper troposphere (UT) were often near or below the detection limit of the measurements (0.005 parts per billion by volume), indicating that background HCl values are much lower than a global mean estimate. However, significant abundances of HCl were observed in many UT air parcels, as a result of stratosphere-to-troposphere transport events. We developed a method for diagnosing the amount of stratospheric ozone in these UT parcels using the compact linear correlation of HCl with ozone found throughout the lower stratosphere (LS). Expanded use of this method will lead to improved quantification of cross-tropopause transport events and validation of global chemical transport models.

Evidence that nitric acid increases relative humidity in low-temperature cirrus clouds.

In situ measurements of the relative humidity with respect to ice (RHi) and of nitric acid (HNO3) were made in both natural and contrail cirrus clouds in the upper troposphere. At temperatures lower than 202 kelvin, RHi values show a sharp increase to average values of over 130% in both cloud types. These enhanced RHi values are attributed to the presence of a new class of HNO3-containing ice particles (Delta-ice). We propose that surface HNO3 molecules prevent the ice/vapor system from reaching equilibrium by a mechanism similar to that of freezing point depression by antifreeze proteins. Delta-ice represents a new link between global climate and natural and anthropogenic nitrogen oxide emissions. Including Delta-ice in climate models will alter simulated cirrus properties and the distribution of upper tropospheric water vapor.

Conditions determining the local stability of populations.

The conditions that determine the local stability classification of an equilibrium population configuration are analyzed. The population investigated is age-structured and density-dependent, where density is determined by an age-weighted population size. 2 demographic parameters are introduced: the marginal birth rate and the marginal death rate, which describe the marginal density-dependence of the birth and death rates of the equilibrium population. Certain necessary and/or sufficient conditions determining stability are developed, most of them involving the net reproduction rate of the population, and examples illustrating these conditions are presented.

Free radicals in the stratosphere: a new observational technique.

A new approach to in situ observations of trace reactive species in the stratosphere is described. A balloon-borne system, floating 40 kilometers above the earth's surface, successfully lowered and then retracted a cluster of instruments a distance of 12 kilometers on a filament of Kevlar. This instrument cluster is capable of detecting gas-phase free radicals at the part-per-trillion level. The suspended instrument array has excellent stability and has been used to measure atomic oxygen concentrations in the stratosphere.

Effects of induced total-body hyperthermia on phosphorus metabolism in humans.

The effects of total-body hyperthermia on phosphorus homeostasis are controversial. To evaluate the problem, 10 clearance studies were performed in seven patients undergoing total-body hyperthermia as an adjunct to the treatment of solid malignant tumors. Total-body hyperthermia was associated with significant reduction in plasma phosphorus concentration from a baseline value of 3.51 +/- 0.18 to 0.6 +/- 0.1 mg/dl (p less than 0.001), returning to baseline following cessation of total-body hyperthermia. The clearance of phosphorus increased from 15.2 +/- 2.5 to 26.1 +/- 3.1 ml per minute (p less than 0.01), and the fractional excretion of phosphorus increased from 11.37 +/- 2.2 to 47.68 +/- 9.7 percent (p less than 0.01). The reduction in plasma phosphorus during total-body hyperthermia was also associated with a significant reduction in the renal threshold phosphorus concentration from 3.17 +/- 0.16 to 0.38 +/- 0.08 (p less than 0.001). The changes in phosphorus homeostasis during total-body hyperthermia were independent of changes in circulating parathyroid hormone level, urinary cyclic AMP excretion, and arterial carbon dioxide tension.

Abortion need and services in the United States, 1974-1975.

More than one million legal abortions were performed in the United States last year--but one-half to three-quarters of a million women in need of abortion services were still unable to obtain them. Ninety percent of all abortions are now performed in the woman's home state, but services are still highly concentrated within states--typically in one or two metropolitan centers where most services are provided by nonhospital clinics. Only one-fourth of hospitals-and fewer than one-fifth of public hospitals-provide any abortion services. Many poor, rural and teenage women who can least afford to travel to obtain legal abortions will continue to be denied access to the services they want and need.