Layer-dependent fMRI allows measurements of information flow in cortical circuits, as afferent and efferent connections terminate in different cortical layers. However, it is unknown to what level human fMRI is specific and sensitive enough to reveal directional functional activity across layers. To answer this question, we developed acquisition and analysis methods for blood-oxygen-level-dependent (BOLD) and cerebral-blood-volume (CBV)-based laminar fMRI and used these to discriminate four different tasks in the human motor cortex (M1). In agreement with anatomical data from animal studies, we found evidence for somatosensory and premotor input in superficial layers of M1 and for cortico-spinal motor output in deep layers. Laminar resting-state fMRI showed directional functional connectivity of M1 with somatosensory and premotor areas. Our findings demonstrate that CBV-fMRI can be used to investigate cortical activity in humans with unprecedented detail, allowing investigations of information flow between brain regions and outperforming conventional BOLD results that are often buried under vascular biases.

Twenty-four pH monitoring the distal esophagus quantitates gastroesophageal reflux in a near physiologic setting by measuring the frequency and duration of acid exposure to the esophageal mucosa. Fifteen asymptomatic volunteers were studies with 24-hour pH and esophageal manometry. The normal cardia was more competent supine than in the upright position. Physiologic reflux was unaffected by age, rarely occurred during slumber, and was the rule after alimentation. One hundred symptomatic pateitns with an abnormal 24-hour pH record (2 S.D. above the mean of controls) could be divided into three patterns of pathological reflux: those who refluxed only in the upright position (9), only in the supine position (37), and in both positions (54). Upright differed from supine refluxers by excessive aerophagia causing reflux episodes by repetitive belching. Compared to controls, they had excessive post-prandial reflux, lower DES pressure, and less DES exposed to the positive pressure of the abdomen. Supine differed from upright refluxers by having a higher incidence of esophagitis and an inability to clear the esophagus of acid after a supine reflux episode. Compared to controls, they had only a lower DES pressure. Combined refluxers had a higher incidence of esophagitis than supine refluxers. Stricture (15%) was seen only in this group. They were similar to supine refluxers in their inability to clear a supine reflux episode. Compared to controls, they had a lower DES pressure and less DES exposed to the positive pressure of the abdomen. Forty of the 100 patients had an antireflux procedure (4 upright, 8 supine, 28 combined). The most severe postoperative flatus and abdominal distention was seen in the upright refluxers. It is concluded that minimal reflux is physiological. Patients with pathological reflux all have lower DES pressure. Patients with upright reflux have less of their DES exposed to the positive pressure environment of the abdomen. Patients with supine reflux have an inability to clear the esophagus of reflux acid and are prone to develop esophagitis. Patients with both upright and supine reflux have the most severe disease and are at risk in developing strictures. In patients with only upright reflux, aerophagia and delayed gastric emptying may be an important etiological factor.

While neuroinflammation is an evolving concept and the cells involved and their functions are being defined, microglia are understood to be a key cellular mediator of brain injury and repair. The ability to measure microglial activity specifically and noninvasively would be a boon to the study of neuroinflammation, which is involved in a wide variety of neuropsychiatric disorders including traumatic brain injury, demyelinating disease, Alzheimer’s disease (AD), and Parkinson’s disease, among others. We have developed [11C]CPPC [5-cyano-N-(4-(4-[11C]methylpiperazin-1-yl)-2-(piperidin-1-yl)phenyl)furan-2-carboxamide], a positron-emitting, high-affinity ligand that is specific for the macrophage colony-stimulating factor 1 receptor (CSF1R), the expression of which is essentially restricted to microglia within brain. [11C]CPPC demonstrates high and specific brain uptake in a murine and nonhuman primate lipopolysaccharide model of neuroinflammation. It also shows specific and elevated uptake in a murine model of AD, experimental allergic encephalomyelitis murine model of demyelination and in postmortem brain tissue of patients with AD. Radiation dosimetry in mice indicated [11C]CPPC to be safe for future human studies. [11C]CPPC can be synthesized in sufficient radiochemical yield, purity, and specific radioactivity and possesses binding specificity in relevant models that indicate potential for human PET imaging of CSF1R and the microglial component of neuroinflammation.

This overview describes the principles of the 4th edition of the European Code against Cancer and provides an introduction to the 12 recommendations to reduce cancer risk. Among the 504.6 million inhabitants of the member states of the European Union (EU28), there are annually 2.64 million new cancer cases and 1.28 million deaths from cancer. It is estimated that this cancer burden could be reduced by up to one half if scientific knowledge on causes of cancer could be translated into successful prevention. The Code is a preventive tool aimed to reduce the cancer burden by informing people how to avoid or reduce carcinogenic exposures, adopt behaviours to reduce the cancer risk, or to participate in organised intervention programmes. The Code should also form a base to guide national health policies in cancer prevention. The 12 recommendations are: not smoking or using other tobacco products; avoiding second-hand smoke; being a healthy body weight; encouraging physical activity; having a healthy diet; limiting alcohol consumption, with not drinking alcohol being better for cancer prevention; avoiding too much exposure to ultraviolet radiation; avoiding cancer-causing agents at the workplace; reducing exposure to high levels of radon; encouraging breastfeeding; limiting the use of hormone replacement therapy; participating in organised vaccination programmes against hepatitis B for newborns and human papillomavirus for girls; and participating in organised screening programmes for bowel cancer, breast cancer, and cervical cancer.