Memory Revisited in Julian Barnes's The Sense of an Ending

An accumulation of years brings with it an accumulation of experiences. The revision of such experiences usually becomes more recurrent after retirement, a transition time from one period of life to another and, as such, a time in which we, human beings, have a tendency to take stock of our lives. This is actually one of the main issues present in Julian Barnes's last novel The Sense of an Ending (2011). When the main protagonist, a retired man quite comfortable and contented with his present life, receives an unexpected inheritance from the mother of a girlfriend from his university years, he is forced to track down a part of his life that he had left at the back of his mind a long time ago. As he explains his story, the protagonist and narrator of the novel raises a number of questions related to the quality and function of memory as one gets into old age. He experiments the unreliability of memory and questions to what extent memory is constructed through the remembered emotions that invaded him over that episode of his life rather than through the events as they actually took place. On the other hand, the act of revisiting and revising that specific episode, brings with it feelings of guilt and remorse as the protagonist realises that his past acts were not as noble as he remembered them to be. However, these acts are part of the past and they cannot be changed; thus, another question that the novel raises is how to account for those actions of which one does not feel proud and, more importantly, how to manage those bad memories as one gets older.

Low-dose theophylline enhances the anti-inflammatory effects of steroids during exacerbations of chronic obstructive pulmonary disease

ABSTRACT Background: Chronic obstructive pulmonary disease (COPD) is characterised by an abnormal inflammatory response mainly to cigarette smoke that flares up during exacerbations of the disease (ECOPD). Reduced activity of histone deacetylases (HDAC) contributes to enhanced inflammation in stable COPD. It was hypothesised that HDAC activity is further reduced during ECOPD and that theophylline, an HDAC activator, potentiates the antiinflammatory effect of steroids in these patients. A study was performed to investigate HDAC activity during ECOPD and the effects of theophylline on the anti-inflammatory effects of steroids in a randomised single-blind controlled study. Methods: 35 patients hospitalised with ECOPD and treated according to international guidelines (including systemic steroids) were randomised to receive or not to receive low-dose oral theophylline (100 mg twice daily). Before treatment and 3 months after discharge, HDAC and nuclear factor-kB (NF-kB) activity in sputum macrophages, the concentration of nitric oxide in exhaled air (eNO) and total antioxidant status (TAS), tumour necrosis factor a (TNFa), interleukin (IL)-6 and IL8 levels in sputum supernatants were measured. Results: Patients receiving standard therapy showed decreased NF-kB activity, eNO concentration and sputum levels of TNFa, IL6 and IL8, as well as increased TAS during recovery of ECOPD, but HDAC activity did not change. The addition of low-dose theophylline increased HDAC activity and further reduced IL8 and TNFa concentrations. Conclusions: During ECOPD, low-dose theophylline increases HDAC activity and improves the anti-inflammatory effects of steroids.

Platelet-activating factor causes ventilation-perfusion mismatch in humans

We hypothesized that platelet-activating factor (PAF), a potent inflammatory mediator, could induce gas exchange abnormalities in normal humans. To this end, the effect of aerosolized PAF (2 mg/ml solution; 24 micrograms) on ventilation-perfusion (VA/Q) relationships, hemodynamics, and resistance of the respiratory system was studied in 14 healthy, nonatopic, and nonsmoking individuals (23 +/- 1 [SEM]yr) before and at 2, 4, 6, 8, 15, and 45 min after inhalation, and compared to that of inhaled lyso-PAF in 10 other healthy individuals (24 +/- 2 yr). PAF induced, compared to lyso-PAF, immediate leukopenia (P < 0.001) followed by a rebound leukocytosis (P < 0.002), increased minute ventilation (P < 0.05) and resistance of the respiratory system (P < 0.01), and decreased systemic arterial pressure (P < 0.05). Similarly, compared to lyso-PAF, PaO2 showed a trend to fall (by 12.2 +/- 4.3 mmHg, mean +/- SEM maximum change from baseline), and arterial-alveolar O2 gradient increased (by 16.7 +/- 4.3 mmHg) (P < 0.02) after PAF, because of VA/Q mismatch: the dispersion of pulmonary blood flow and that of ventilation increased by 0.45 +/- 0.1 (P < 0.01) and 0.29 +/- 0.1 (P < 0.04), respectively. We conclude that in normal subjects, inhaled PAF results in considerable immediate VA/Q inequality and gas exchange impairment. These results reinforce the notion that PAF may play a major role as a mediator of inflammation in the human lung.

Platelet-activating factor causes ventilation-perfusion mismatch in humans

We hypothesized that platelet-activating factor (PAF), a potent inflammatory mediator, could induce gas exchange abnormalities in normal humans. To this end, the effect of aerosolized PAF (2 mg/ml solution; 24 micrograms) on ventilation-perfusion (VA/Q) relationships, hemodynamics, and resistance of the respiratory system was studied in 14 healthy, nonatopic, and nonsmoking individuals (23 +/- 1 [SEM]yr) before and at 2, 4, 6, 8, 15, and 45 min after inhalation, and compared to that of inhaled lyso-PAF in 10 other healthy individuals (24 +/- 2 yr). PAF induced, compared to lyso-PAF, immediate leukopenia (P < 0.001) followed by a rebound leukocytosis (P < 0.002), increased minute ventilation (P < 0.05) and resistance of the respiratory system (P < 0.01), and decreased systemic arterial pressure (P < 0.05). Similarly, compared to lyso-PAF, PaO2 showed a trend to fall (by 12.2 +/- 4.3 mmHg, mean +/- SEM maximum change from baseline), and arterial-alveolar O2 gradient increased (by 16.7 +/- 4.3 mmHg) (P < 0.02) after PAF, because of VA/Q mismatch: the dispersion of pulmonary blood flow and that of ventilation increased by 0.45 +/- 0.1 (P < 0.01) and 0.29 +/- 0.1 (P < 0.04), respectively. We conclude that in normal subjects, inhaled PAF results in considerable immediate VA/Q inequality and gas exchange impairment. These results reinforce the notion that PAF may play a major role as a mediator of inflammation in the human lung.

Hippocampal Theta-Phase Modulation of Replay Correlates with Configural-Relational Short-Term Memory Performance

Thereis now growing evidencethatthe hippocampus generatestheta rhythmsthat can phase biasfast neural oscillationsinthe neocortex, allowing coordination of widespread fast oscillatory populations outside limbic areas. A recent magnetoencephalographic study showed that maintenance of configural-relational scene information in a delayed match-to-sample (DMS) task was associated with replay of that information during the delay period. The periodicity of the replay was coordinated by the phase of the ongoing theta rhythm, and the degree of theta coordination during the delay period was positively correlated with DMS performance. Here, we reanalyzed these data to investigate which brain regions were involved in generating the theta oscillations that coordinated the periodic replay of configural- relational information. We used a beamformer algorithm to produce estimates of regional theta rhythms and constructed volumetric images of the phase-locking between the local theta cycle and the instances of replay (in the 13- 80 Hz band). We found that individual differences in DMS performancefor configural-relational associations were relatedtothe degree of phase coupling of instances of cortical reactivations to theta oscillations generated in the right posterior hippocampus and the right inferior frontal gyrus. This demonstrates that the timing of memory reactivations in humans is biased toward hippocampal theta phase