1918 Influenza Pandemic and Highly Conserved Viruses with Two Receptor-Binding Variants

The “Spanish influenza pandemic swept the globe in the autumn and winter of 1918–19, and resulted in the deaths of approximately 40 million people. Clinically, epidemiologically, and pathologically, the disease was remarkably uniform, which suggests that similar viruses were causing disease around the world. To assess the homogeneity of the 1918 pandemic influenza virus, partial hemagglutinin gene sequences have been determined for five cases, including two newly identified samples from London, United Kingdom. The strains show 98.9% to 99.8% nucleotide sequence identity. One of the few differences between the strains maps to the receptor-binding site of hemagglutinin, suggesting that two receptor-binding configurations were co-circulating during the pandemic. The results suggest that in the early stages of an influenza A pandemic, mutations that occur during replication do not become fixed so that a uniform “consensus” strain circulates for some time

Episodic hypoxia evokes long-term facilitation of genioglossus muscle activity in neonatal rats

The aim of this study was to determine if episodic hypoxia evokes persistent increases of genioglossus muscle (GG) activity, termed long-term facilitation (LTF), in neonatal rats in vivo. Experiments were performed on anaesthetized, spontaneously breathing, intubated neonatal rats (postnatal days (P) 3–7), divided into three groups. The first group (n = 8) was subjected to three 5-min periods of hypoxia (5% O(2)–95% N(2)) alternating with 5 min periods of room air. The second group (n = 8) was exposed to 15 min of continuous hypoxia. The third (n = 4) group was not exposed to hypoxia and served as a control. GG EMG activity and airflow were recorded before, during and for 60 min after episodic and continuous hypoxic exposure. During hypoxia, GG EMG burst amplitude and tidal volume (V(T)) significantly increased compared to baseline levels (episodic protocol: mean ±s.e.m.; 324 ± 59% of control and 0.13 ± 0.007 versus 0.09 ± 0.005 ml, respectively; continuous protocol: 259 ± 30% of control and 0.16 ± 0.005 versus 0.09 ± 0.007 ml, respectively; P < 0.05). After the episodic protocol, GG EMG burst amplitude transiently returned to baseline; over the next 60 min, burst amplitude progressively increased to levels significantly greater than baseline (238 ± 40% at 60 min; P < 0.05), without any significant increase in V(T) and respiratory frequency (P> 0.05). After the continuous protocol, there was no lasting increase in GG EMG burst amplitude. We conclude that LTF of upper airway muscles is an adaptive respiratory behaviour present from birth

Evaluation and application of the CPM Dairy Nutrition model

The Cornell-Penn-Miner (CPM) Dairy is an applied mathematical nutrition model that computes dairy cattle requirements and the supply of energy and nutrients based on characteristics of the animal, the environment and the physicochemical composition of the feeds under diverse production scenarios. The CPM Dairy was designed as a steady-state model to use rates of degradation of feed carbohydrate and protein and the rate of passage to estimate the extent of ruminal fermentation, microbial growth, and intestinal digestibility of carbohydrate and protein fractions in computing energy and protein post-rumen absorption, and the supply of metabolizable energy and protein to the animal. The CPM Dairy version 3.0 (CPM Dairy 3.0) includes an expanded carbohydrate fractionation scheme to facilitate the characterization of individual feeds and a sub-model to predict ruminal metabolism and intestinal absorption of long chain fatty acids. The CPM Dairy includes a non-linear optimization algorithm that allows for least-cost formulation of diets while meeting animal performance, feed availability and environmental restrictions of modern dairy cattle production. When the CPM Dairy 3.0 was evaluated with data of 228 individual lactating dairy cows containing appropriate information including observed dry matter intake, the linear regression between observed and model-predicted milk production values indicated the model was able to account for 79.8% of the variation. The concordance correlation coefficient (CCC) was high (rc=0.89) without a significant mean bias (0.52 kg/d; P=0.12). The accuracy estimated by the CCC was 0.997. The root of mean square error of prediction (MSEP) was 5.14 kg/d (0.16 of the observed mean) and 87.3% of the MSEP was due to random errors, suggesting little systematic bias in predicting milk production of high-producing dairy cattle. Based upon these evaluations, it was concluded the CPM Dairy 3.0 model adequately predicts milk production at the farm level when appropriate animal characterization, feed composition and feed intake are provided; however, further improvements are needed to account for individual animal variation

Distinct inspiratory rhythm and pattern generating mechanisms in the preBötzinger complex.

In the mammalian respiratory central pattern generator, the preBötzinger complex (preBötC) produces rhythmic bursts that drive inspiratory motor output. Cellular mechanisms initiated by each burst are hypothesized to be necessary to determine the timing of the subsequent burst, playing a critical role in rhythmogenesis. To explore mechanisms relating inspiratory burst generation to rhythmogenesis, we compared preBötC and hypoglossal (XII) nerve motor activity in medullary slices from neonatal mice in conditions where periods between successive inspiratory XII bursts were highly variable and distributed multimodally. This pattern resulted from rhythmic preBötC neural population activity that consisted of bursts, concurrent with XII bursts, intermingled with significantly smaller "burstlets". Burstlets occurred at regular intervals during significantly longer XII interburst intervals, at times when a XII burst was expected. When a preBötC burst occurred, its high amplitude inspiratory component (I-burst) was preceded by a preinspiratory component that closely resembled the rising phase of burstlets. Cadmium (8 μM) eliminated preBötC and XII bursts, but rhythmic preBötC burstlets persisted. Burstlets and preinspiratory activity were observed in ~90% of preBötC neurons that were active during I-bursts. When preBötC excitability was raised significantly, burstlets could leak through to motor output in medullary slices and in vivo in adult anesthetized rats. Thus, rhythmic bursting, a fundamental mode of nervous system activity and an essential element of breathing, can be deconstructed into a rhythmogenic process producing low amplitude burstlets and preinspiratory activity that determine timing, and a pattern-generating process producing suprathreshold I-bursts essential for motor output

Improving Fidelity of Translation of the Stepping On Falls Prevention Program through Root Cause Analysis

Background: Fidelity monitoring is essential with implementation of complex health interventions, but there is little description of how to use results of fidelity monitoring to improve the draft program package prior to widespread dissemination. Root cause analysis (RCA) provides a systematic approach to identifying underlying causes and devising solutions to prevent errors in complex processes. Its use has not been described in implementation science.Methods: Stepping On is a small group, community-based intervention that has been shown to reduce falls by 31%. To prepare Stepping On for widespread U.S. dissemination, we conducted a pilot of the draft program package, monitoring the seven Stepping On sessions for fidelity of program delivery, and assessing participant receipt and enactment through participant interviews after the workshop. Lapses to fidelity in program delivery, receipt, and enactment were identified. We performed a root cause analysis to identify underlying causes of, and solutions to, such lapses, with the goal of preventing fidelity lapses with widespread dissemination.Results: Lapses to fidelity in program delivery were in the domains of group leader’s role, use of adult learning principles, and introducing and upgrading the exercises. Lapses in fidelity of participant receipt and enactment included lack of knowledge about balance exercises and reduced adherence to frequency of exercise practice and advancement of exercise. Root causes related to leader training and background, site characteristics and capacity, and participant frailty and expectations prior to starting the program. The RCA resulted in changes to the program manual, the training program and training manual for new leaders, and to the methods for and criteria for participant and leader recruitment. A Site Implementation Guide was created to provide information to sites interested in the program.Conclusions: Disseminating complex interventions can be done more smoothly by first using a systematic quality improvement technique, such as the RCA, to identify how lapses in fidelity occur during the earliest stages of implementation. This technique can also help bring about solutions to these lapses of fidelity prior to widespread dissemination across multiple domains lapses