In vivo detection of clinically non-apparent ocular surface inflammation in patients with meibomian gland dysfunction-associated refractory dry eye symptoms: a pilot study.

PURPOSE: The utility of in vivo confocal microscopy (IVCM) in the investigation of palpebral conjunctival and corneal inflammation in patients with meibomian gland dysfunction (MGD)-associated refractory dry eye symptoms following gland expression, despite objective clinical improvement. METHODS: A retrospective, observational pilot study was conducted evaluating five patients with MGD-associated refractory dry eye symptoms and three control groups: symptomatic untreated MGD patients (n=3), treatment-responsive MGD patients with improved symptoms (n=3) and asymptomatic healthy normals (n=11). Ocular surface disease index (OSDI) scores, tear break-up time (TBUT), the number of meibomian glands yielding liquid secretion (MGYLS), palpebral conjunctival epithelial and substantia propria immune cell (EIC, SIC), and corneal dendritic cell (DC) densities were measured. RESULTS: Despite clinical improvement (TBUT: 6.4±1.2 s to 10.1±2.1 s, P=0.03; MGYLS: 3.5±0.8 glands to 7.0±1.1 glands, P=0.13) and a normal clinical examination post treatment, MGD patients remained symptomatic. IVCM revealed increased immune cells in the palpebral conjunctiva (refractory MGD EIC=592.6±110.1 cells/mm2 untreated MGD EIC=522.6±104.7 cells/mm2, P=0.69; responsive MGD EIC=194.9±119.4 cells/mm2, P<0.01; normals EIC=123.7±19.2 cells/mm2, P< 0.001), but not the cornea (refractory MGD DC=60.9±28.3 cells/mm2; normals DC=25.9±6.3 cells/mm2; P=0.43). EIC did not correlate with TBUT (Rs=-0.26, P=0.33). OSDI scores correlated with both EIC (Rs=0.76, P<0.001) and TBUT (Rs=-0.69, P<0.01) but not SIC. Intraglandular immune cells were also seen. CONCLUSION: MGD-associated refractory symptoms and the symptom-sign disparity may be explained by clinically non-apparent, active inflammation of the palpebral conjunctiva as detected by IVCM. These patients may benefit from anti-inflammatory therapy.

The relationship between serial monogamy and rape in the United States (1960-1995).

In mating systems where individuals pair, separate and re-pair repeatedly (i.e. serial monogamy), some males monopolize more than one female's reproductive life span and thus leave other males effectively mateless. Males who cannot secure females through traditional methods may seek alternatives, such as rape, to ensure gene passage into future generations. Analysis of US government records shows that (i) divorce and remarriage patterns in the United States are likely to increase the variance in male reproductive success, and (ii) rates of divorce and rape correlate positively. The former result suggests that serial monogamy increases the variance in male, relative to female, reproductive success and the latter result suggests that this variance influences the frequency of rape in American society. Because raped females sometimes become pregnant and take these pregnancies to term, our results indicate that rape has current adaptive significance.

Fever in honeybee colonies.

Honeybees, Apis spp., maintain elevated temperatures inside their nests to accelerate brood development and to facilitate defense against predators. We present an additional defensive function of elevating nest temperature: honeybees generate a brood-comb fever in response to colonial infection by the heat-sensitive pathogen Ascosphaera apis. This response occurs before larvae are killed, suggesting that either honeybee workers detect the infection before symptoms are visible, or that larvae communicate the ingestion of the pathogen. This response is a striking example of convergent evolution between this "superorganism" and other fever-producing animals.

Stability analysis of two linear accommodation and convergence models.

PURPOSE: To perform time domain stability analysis on two widely accepted linear models of accommodation and convergence. METHODS: For each model, the governing differential equations were used to compute the system matrix. The system matrices were used to calculate the respective trace and determinant from which eigen-vectors and eigenvalues were quantified. These characteristic numbers fully identified and classified the fixed points of each model and, thus, their stability. RESULTS: Controller gains, time constants, and accommodation and convergence cross-links determined model stability. Accommodation and convergence cross-links have the greatest influence on stability. A model-specific transition between stabilities was identified as the product of these cross-links, AC.CA(CRITICAL). For each model, three types of fixed points are described and displayed graphically: stable node, line of nonisolated fixed points, and saddle. CONCLUSION: We demonstrated the stability analysis of a two-dimensional linear system, working only in the time domain. The benefit of time-domain stability analysis is that it can be extended to nonlinear systems when frequency domain analysis techniques fail. Given that we live in a fundamentally nonlinear world and that the use and application of computational models is extensive, this is a valuable and important tool.

Safety and antitumor activity of recombinant soluble Apo2 ligand.

TNF and Fas ligand induce apoptosis in tumor cells; however, their severe toxicity toward normal tissues hampers their application to cancer therapy. Apo2 ligand (Apo2L, or TRAIL) is a related molecule that triggers tumor cell apoptosis. Apo2L mRNA is expressed in many tissues, suggesting that the ligand may be nontoxic to normal cells. To investigate Apo2L's therapeutic potential, we generated in bacteria a potently active soluble version of the native human protein. Several normal cell types were resistant in vitro to apoptosis induction by Apo2L. Repeated intravenous injections of Apo2L in nonhuman primates did not cause detectable toxicity to tissues and organs examined. Apo2L exerted cytostatic or cytotoxic effects in vitro on 32 of 39 cell lines from colon, lung, breast, kidney, brain, and skin cancer. Treatment of athymic mice with Apo2L shortly after tumor xenograft injection markedly reduced tumor incidence. Apo2L treatment of mice bearing solid tumors induced tumor cell apoptosis, suppressed tumor progression, and improved survival. Apo2L cooperated synergistically with the chemotherapeutic drugs 5-fluorouracil or CPT-11, causing substantial tumor regression or complete tumor ablation. Thus, Apo2L may have potent anticancer activity without significant toxicity toward normal tissues.

An extension of an accommodation and convergence model of emmetropization to include the effects of illumination intensity.

The Flitcroft (1998) emmetropization model incorporates a classical model of accommodation and convergence with blur-driven feedback control of eye growth. We have modified this model by incorporating the effects of illumination (with or without extensive near work) on accommodation, vergence, pupil diameter and emmetropization. In addition to replicating Flitcroft's results, we show that (1) decreased illumination and (2) a low convergence accommodation/convergence (CAC) ratio exacerbate the progression of near-work-induced myopia. Our model further indicates that prescription of negative lenses, under these conditions, augments the advancement of myopia.

Promoting health in young people.

This article discusses aspects of health that might affect young people and ways in which nurses can promote healthy living and support this group of clients during a potential period of anxiety.

Teenage health and the practice nurse: choice and opportunity for both?

Teenage health issues and the means to address them have caused increasing concern over recent years. This study investigated the involvement and training of practice nurses, the topics raised during consultations with teenagers, and the comfort of the practice nurses in dealing with these topics. Data were collected using a postal questionnaire survey (response rate 80.6%). Expansion of the role of the practice nurse in teenage health may be appropriate but needs to be supported by training.

Refraction and keratometry: departures from and transformations toward multivariate normality.

The multivariate distributional properties of refraction and keratometric data were investigated across eyes with power represented in the coordinate system introduced by Deal and Toop. Normality and departure from normality were assessed with the aid of chi 2 and normal probability plots and by the comparison of multivariate sample skewness and kurtosis with critical values. Two of the three data sets show significant departure from normality in each of the marginal distributions and, therefore, the joint distribution too. The keratometric data were normally distributed along the line of spherical powers but departed from normality in the astigmatic plane. Marginal transformations are used to reduce the departure from normality where necessary. The transformation that was found to be successful is essentially an example of a Box/Cox transformation involving a shift, ci, and an exponent, gamma i, where i = 1,2,3. For two of the data sets, the values of the exponent, gamma i, result in a transformation that is similar to a modified square root transformation.