Agonistic 4-1BB antibody fails to reduce disease burden during acute respiratory syncytial virus (RSV) infection.

Respiratory Syncytial Virus (RSV) remains a leading cause of infant morbidity and mortality worldwide. Despite this, there are limited therapeutic options. CD8 T cells have an integral role in controlling viral infections; strategies to enhance these responses may be clinically relevant. The T cell costimulatory receptor, 4-1BB, is known to play a role in expansion of antiviral CD8 T cells. In this study, we examined the effect of agonistic 4-1BB antibody at the time of RSV infection in mice. We show that this antibody did not improve outcomes in the setting of RSV infection but rather, led to increased weight loss and a reduction in RSV specific CD8 T cells in the lung. This work suggests caution in the use of agonistic 4-1BB antibody in the setting of viral infections.

Treatment of heavy metals by iron oxide coated and natural gravel media in Sustainable urban Drainage Systems.

Sustainable urban Drainage Systems (SuDS) filter drains are simple, low-cost systems utilized as a first defence to treat road runoff by employing biogeochemical processes to reduce pollutants. However, the mechanisms involved in pollution attenuation are poorly understood. This work aims to develop a better understanding of these mechanisms to facilitate improved SuDS design. Since heavy metals are a large fraction of pollution in road runoff, this study aimed to enhance heavy metal removal of filter drain gravel with an iron oxide mineral amendment to increase surface area for heavy metal scavenging. Experiments showed that amendment-coated and uncoated (control) gravel removed similar quantities of heavy metals. Moreover, when normalized to surface area, iron oxide coated gravels (IOCGs) showed poorer metal removal capacities than uncoated gravel. Inspection of the uncoated microgabbro gravel indicated that clay particulates on the surface (a natural product of weathering of this material) augmented heavy metal removal, generating metal sequestration capacities that were competitive compared with IOCGs. Furthermore, when the weathered surface was scrubbed and removed, metal removal capacities were reduced by 20%. When compared with other lithologies, adsorption of heavy metals by microgabbro was 10-70% higher, indicating that both the lithology of the gravel, and the presence of a weathered surface, considerably influence its ability to immobilize heavy metals. These results contradict previous assumptions which suggest that gravel lithology is not a significant factor in SuDS design. Based upon these results, weathered microgabbro is suggested to be an ideal lithology for use in SuDS.

Waterborne radon in seven Maine schools.

This study investigated the transfer coefficient of radon from water to air in kitchens and bathrooms for seven schools located in Maine. Simulations occurred in water use rooms containing multiple airborne radon detectors. Quantities measured included radon concentration in water (10-960 Bq L(-1), 260-26,000 pCi L(-1)), air (0-3 Bq L(-1), 0-80 pCi L(-1)), volume of water used, emissivities (0.04-0.98), and ventilation rates (0.012-0.066 min). Using these parameters provides the means for calculating the transfer coefficient and by which dose due to waterborne radon can be estimated in other schools. Transfer coefficient values calculated for kitchens and baths ranged from 9.6 x 10(-6) to 2.0 x 10(-2). Multiple detectors showed that the radon concentration varied throughout a room. These measurements represent the first of this type to be done in schools in Maine.

Causes of hair loss and the developments in hair rejuvenation.

Hair is considered to be a major component of an individual's general appearance. The psychological impact of hair loss results in a measurably detrimental change in self-esteem and is associated with images of reduced worth. It is not surprising that both men and women find hair loss a stressful experience. Genetic hair loss is the major problem affecting men and by the age of 50, up to 50% will be affected. Initial attempts to regenerate the lost hair have centred on applying a topical solution of between 2% to 5% minoxidil; however, the results proved disappointing. Recently, finasteride, a type II 5alpha reductase inhibitor has been found to regrow a noticeable amount of hair in about 40% of balding men. Further developments in treatments have lead to the use of a dual type I and type II inhibitor where 90% of those treated regrow a noticeable amount of hair. In women the major cause of hair loss before the age of 50 is nutritional, with 30% affected. Increased and persistent hair shedding (chronic telogen effluvium) and reduced hair volume are the principle changes occurring. The main cause appears to be depleted iron stores, compromised by a suboptimal intake of the essential amino acid l-lysine. Correction of these imbalances stops the excessive hair loss and returns the hair back to its former glory. However, it can take many months to redress the situation.

An in-vitro comparison of controlled release aminophylline tablets: Phyllocontin Continus and Pecram.

It has been suggested that two controlled release preparations containing aminophylline, Phyllocontin Continus and Pecram, are clinically equivalent and are therefore interchangeable. In this study, an in-vitro evaluation of the two preparations was completed using the British Pharmacopoeia dissolution apparatus, initially using water and then an acid/buffer medium to provide a similar pH environment to that within the gastrointestinal tract. Similar release profiles were found when water was used as the dissolution medium, with very little variation between tablets within each group. Good fits were obtained for dissolution-controlled release and diffusion-controlled release models. When the acid/buffer solution was used as the dissolution medium a reduction in the rate of release was observed with Phyllocontin. It was predicted that if this was repeated in-vivo then differences in the peak plasma levels between the two formulations would be seen, although these may be masked by the other variables encountered.

Natural progression of male pattern baldness in young men.

Twenty-six men who presented with male pattern baldness (androgen-dependent alopecia), were quantitatively evaluated for scalp hair variables and compared with 13 age-matched controls. Compared to controls, significant mean differences for hair variables were found in the frontal-vertex area, while in the occipital area, a reduction in total hair density (hairs/cm2) was the only significant (P less than 0.05) finding. A large proportion (48.5%) of meaningful hair (non-vellus hair) was less than or equal to 40 mm in length, yet had diameters similar to hairs growing much longer. In controls, these hairs accounted for only 12.2% of the total population. Compared to baseline, mean values from the frontal-vertex area of subjects with androgen-dependent alopecia were significantly lower for total hair density, meaningful hair density (non-vellus hairs/cm2) and percentage of hair in the anagen growth phase, 12 and 24 months later. During this time, total hair density decreased by 6.5% after 12 months and by 11.9% after 24 months. Similarly, meaningful hair density declined at 12 months by 10.8% and by 22.7% after 24 months. No change in any hair variable was detected in controls after 12 or 24 months. Our findings suggest that medications capable of maintaining the existing hair population should be regarded as effective treatments for this condition. Left untreated androgen-dependent alopecia progressively deteriorates. The induction of non-vellus hairs less than or equal to 40 mm in length to grow longer, would substantially improve the aesthetic profile without the need to generate new hair.

Biochemical and trichological characterization of diffuse alopecia in women.

One hundred women who presented with diffuse alopecia, were quantitatively evaluated for hair variables and compared with 20 controls. Fifty were selected for biochemical and haematological investigations, 44 of whom also underwent endocrine evaluation. Compared to controls, significant changes in hair values were found in the frontal area of all subjects, while 84% had significant changes in the occipital area. A biphasic distribution of hair diameter was evident in subjects who had percentages of vellus hair and telogen hair less than or equal to 30 mm in length that were above the control ranges. No significant difference between the mean hormonal values of women with diffuse alopecia and controls could be found. No correlation between hair values and individual or combined hormonal levels could be established. In 18 subjects (40.9%) hormonal values were within the control ranges and these apparently normal findings were often associated with adverse hair profiles. A raised dihydrotestosterone was found in 13 subjects (29.5%) and was the most frequently elevated androgenic finding. Seventeen (34.0%) had changes in iron metabolism, while in 36 (72.0%) serum ferritin levels were below the lowest control value. All had a decrease in the percentage of hair in the anagen growth phase compared to controls. The hair changes were similar to those observed in genetic hair loss in men, a proven androgen-dependent condition. We propose that diffuse androgen-dependent alopecia is the appropriate name to describe this condition in these women.

Amino-acid composition in trichorrhexis nodosa.

Trichorrhexis nodosa is a common shaft defect affecting scalp hair. Two-hundred scalp hairs exhibiting trichorrhexis nodosa were obtained from two normal females; samples were prepared from proximal shaft, pre-nodule, nodule and post-nodule sections and analysed for their respective amino-acid compositions. Significant reductions in cystine (P less than 0.001) of the pre-nodule, nodule and post-nodule sections, which decreased by 17.2%, 19.8% and 14.3%, respectively, and an increase in the acidic amino acids (P less than 0.03) were found, compared to values obtained from proximal shaft of the same hairs. The majority of nodules occurred within the last 10% of the shaft, and the similarity in amino-acid compositions between pre-nodule, nodule and post-nodule sections suggests that 'weathering' is the major factor influencing nodule occurrence. It is postulated that nodule formation requires a specific degree of exposure to 'weathering' together with a reduction in cuticle cell coverage. It is suggested that an initial structural defect, created by a change in the DNA coding for a cuticle polypeptide fraction, could be responsible for the selective and isolated presentation of the nodule within a 'weathered' section of hair shaft.

Treatment of essential telangiectasia: effects of increasing concentrations of polidocanol.

A double-blind, double-paired comparison study was performed to evaluate the effects of increasing concentrations of polidocanol in the sclerotherapy of essential telangiectasias of the legs. Polidocanol 0.25%, 0.50%, 0.75%, and 1.0% were compared with regard to clinical effectiveness, safety, and patient acceptance. All dosages were well tolerated by the patients. There were no allergic reactions to polidocanol and no cases of superficial ulceration nor necrosis. Among those whose veins cleared, there was little difference in time to clearing for the four concentrations, which averaged three to four treatment sessions. No statistically significant differences existed among the four dosages with respect to level of improvement, itching, or neovascularization. Polidocanol 0.75% and 1.0%, however, caused more side effects noted by patients and induced more hyperpigmentation than did the lower concentrations. Polidocanol 0.25% yielded the lowest percentage of patients whose veins cleared. The 0.50% solution was the most effective concentration for total overall clearing of the types of vessels treated in this study. From this information it appears that 0.50% polidocanol may be the sclerosing agent of choice.

Spouse selection in Canada, 1921-78: an examination by age, sex and religion.

PIP: This paper presents time series data on spouse selection in Canada for the period 1921-1978. Homogamous and endogamous trends are examined by age, sex, and religion. In the case of religious endogamy, most groups have shown decreasing proportions of marriages. There are also considerable differences in rates of endogamy among religious groups, and these differences have largely persisted over time. Until 1971, the proportions of brides marrying older and younger grooms decreased, while the proportion marrying the same age increased, after which these trends reversed. Younger males increasingly tended to select brides of their own age group until the 1960s, while older males have been increasingly heterogamous since World War II. While these changes in spouse selection have been examined with respect to changes in the unmarried population, the relation between the 2 trends is not clear, and it is difficult to account fully for the observed trends in spouse selection with respect to age.^ieng

Effect of Eperythrozoon ovis on the lysis of sheep erythrocytes in the complement fixation test.

When erythrocytes from sheep experimentally infected with Eperythrozoon ovis were used in the titration of reagents for a standardised complement fixation test, increased amounts of both haemolysin and complement were required for erythrocyte lysis compared with preinfection titrations. The haemolysin requirement increased by up to 125% at 55 days post-infection and complement requirement increased by up to 40% at 40 days post-infection. These changes appeared to correlate with the development of a macrocytic anaemia in affected sheep rather than E. ovis parasitaemia. The results emphasise the need to carefully monitor the haematological parameters of sheep used as sources of erythrocytes for the complement fixation test.

A reappraisal of the complement fixation test using soluble Mycobacterium avium antigen for the detection of M. paratuberculosis infection in cattle.

Serums from 263 cattle suspected of having paratuberculosis on the basis of clinical signs, were tested for antibodies to Mycobacterium paratuberculosis with a complement fixation test (CFT) employing a heat extracted, soluble M. avium antigen. Microscopic examination confirmed that 172 (65.4%) clinically affected animals had paratuberculosis, the remainder being disease-free. The specificity and sensitivity of the CFT was 92.3% and 74.4% respectively. Phenol treatment of serums before testing was compared with no treatment and was found to have no significant effect on the CFT titres. Results obtained are discussed in relation to the cause of false negative and false positive reactions.

Experimental infection of goats with Brucella ovis.

Six goats were inoculated with Brucella ovis. Two goats were inoculated with infected semen by the intratesticular route and 2 each by installation of the semen on to the nasal or preputial epithelium. All goats produced antibody responses as measured by an enzyme-linked immunosorbent assay (ELISA) procedure and the serums of 5 goats reacted in complement fixation tests for B. ovis. The 2 goats inoculated by the intratesticular route and one receiving B. ovis instilled intranasally subsequently excreted B. ovis in their semen. The possibility of natural transmission is discussed.

Epidemiological studies on ovine brucellosis in selected ram flocks.

The epidemiology of ovine brucellosis was investigated in 6 ram flocks in which anomalous reactions to the complement fixation test was recorded. It was shown that rams can become infected as young as 4 months of age. Naturally infected animals have an epididymitis and excrete Brucella ovis in their semen or they may only show a serological response for a short time then recover. The base line titres of chronically infected animals stay relatively constant. The importance of abortive infection and possible reinfection is discussed.