Nomographic representation of logistic regression models: a case study using patient self-assessment data

Logistic regression models are widely used in medicine, but difficult to apply without the aid of electronic devices. In this paper, we present a novel approach to represent logistic regression models as nomograms that can be evaluated by simple line drawings. As a case study, we show how data obtained from a questionnaire-based patient self-assessment study on the risks of developing melanoma can be used to first identify a subset of significant covariates, build a logistic regression model, and finally transform the model to a graphical format. The advantage of the nomogram is that it can easily be mass-produced, distributed and evaluated, while providing the same information as the logistic regression model it represents.     

New insights into water transport and edema in the central nervous system from phenotype analysis of aquaporin-4 null mice

Aquaporin-4 (AQP4) is the major water channel in the CNS. Its expression at fluid-tissue barriers (blood-brain and brain-cerebrospinal fluid barriers) throughout the brain and spinal cord suggests a role in water transport under normal and pathological conditions. Phenotype studies of transgenic mice lacking AQP4 have provided evidence for a role of AQP4 in cerebral water balance and neural signal transduction. Primary cultures of astrocytes from AQP4-null mice have greatly reduced osmotic water permeability compared with wild-type astrocytes, indicating that AQP4 is the principal water channel in these cells. AQP4-null mice have reduced brain swelling and improved neurological outcome following water intoxication and focal cerebral ischemia, establishing a role of AQP4 in the development of cytotoxic (cellular) cerebral edema. In contrast, brain swelling and clinical outcome are worse in AQP4-null mice in models of vasogenic (fluid leak) edema caused by freeze-injury and brain tumor, probably due to impaired AQP4-dependent brain water clearance. AQP4-null mice also have markedly reduced acoustic brainstem response potentials and significantly increased seizure threshold in response to chemical convulsants, implicating AQP4 in modulation of neural signal transduction. Pharmacological modulation of AQP4 function may thus provide a novel therapeutic strategy for the treatment of stroke, tumor-associated edema, epilepsy, traumatic brain injury, and other disorders of the CNS associated with altered brain water balance.     

The response of Golgi tendon organs to single motor unit contractions.

1. Cross-correlation analysis has been used to quantify the responses of cat soleus tendon organs to repetitive twitch contractions of: (a) different motor units within the muscle, (b) single motor units at different muscle lengths, and (c) single motor units when the pulse-train pattern of stimulation delivered to the motor unit axon was altered. 2. Ib afferents were observed which responded to each of several hundred successive motor unit twitches with identical numbers of spikes and with relatively invariant latencies. 3. The present results show that tendon organs are sensitive to subtle alterations in motor unit twitch wave form and amplitude, and that this sensitivity is reflected in the precise timings of their afferent discharge. 4. Examination of these tendon organ responses indicates that the forces produced by single motor units couples to the receptor capsule are well above threshold. Calculations based on these results, and earlier soleus motor unit and muscle fibre data, suggest that the absolute force threshold for tendon organs may be as little as 4 mg, which is less than the estimated minimum twitch force generated by individual soleus muscle fibres. 5. Considering the number of tendon organs in a muscle, and the likelihood that every motor unit is connected with at least one receptor, the sensitivity of tendon organs ensures that every twitch of every motor unit will be reflected in the population of afferent signals projecting to the spinal cord.     

DNase pretreatment of master mix reagents improves the validity of universal 16S rRNA gene PCR results

DNase I pretreatment of 16S rRNA gene PCR reagents was tested. The DNase I requirement for the elimination of false-positive results varied between 0.1 and 70 IU per master mix depending on the applied Taq polymerase. PCR sensitivity was mostly maintained when 0.1 IU of DNase I was used.     

Correlation of light and electron micrographs of human metaphase chromosomes after incorporation of BUdR and staining with "33258 Hoechst" and Giemsa.

Stained (Giemsa, "33258 Hoechst"1) and "33258 Hoechst" + Giemsa) and unstained metaphase chromosomes from human peripheral lymphocytes, after two rounds of replication in the presence of 5-bromodeoxyuridine (BUdR), have been prepared for electron microscopy. There is a positive correlation between light and electron micrographs. The same differential contrast on electron micrographs has been obtained whether the preparations have been stained or not. We attribute this differential contrast primarily to the lesser condensation of the bifilarly substituted chromatid.     

Histone deposition protein Asf1 maintains DNA replisome integrity and interacts with replication factor C

Chromatin assembly and DNA replication are temporally coupled, and DNA replication in the absence of histone synthesis causes inviability. Here we demonstrate that chromatin assembly factor Asf1 also affects DNA replication. In budding yeast cells lacking Asf1, the amounts of several DNA replication proteins, including replication factor C (RFC), proliferating cell nuclear antigen (PCNA), and DNA polymerase epsilon (Pol epsilon), are reduced at stalled replication forks. In contrast, DNA polymerase alpha (Pol alpha) accumulates to higher than normal levels at stalled forks in asf1Delta cells. Using purified, recombinant proteins, we demonstrate that RFC directly binds Asf1 and can recruit Asf1 to DNA molecules in vitro. We conclude that histone chaperone protein Asf1 maintains a subset of replication elongation factors at stalled replication forks and directly interacts with the replication machinery.