The value of an integrated approach for understanding the neocortex by combining functional characterization of single neuron activity with the underlying circuit architecture has been understood since the dawn of modern neuroscience. However, in practice, anatomical connectivity and physiology have been studied mostly separately. Following in the footsteps of previous studies that have combined physiology and anatomy in the same tissue, here we present a unique functional connectomics dataset that contains calcium imaging of an estimated 75,000 neurons from primary visual cortex (VISp) and three higher visual areas (VISrl, VISal and VISlm), that were recorded while a mouse viewed natural movies and parametric stimuli. The functional data were co-registered with electron microscopy (EM) data of the same volume which were automatically segmented, reconstructing more than 200,000 cells (neuronal and non-neuronal) and 524 million synapses. Subsequent proofreading of some neurons in this volume yielded reconstructions that include complete dendritic trees as well the local and inter-areal axonal projections. The largest proofread excitatory axon reached a length of 19 mm and formed 1,893 synapses, while the largest inhibitory axon formed 10,081 synapses. Here we release this dataset as an open access resource to the scientific community including a set of analysis tools that allows easy data access, both programmatically and through a web user interface.

When macaque monkeys view achromatic, sinusoidal gratings of a single spatial frequency, the pattern of 14C-2-deoxy-d-glucose (DG) uptake produced by the gratings is shown to depend on the spatial frequency chosen. When a relatively high (5-7 cycles/deg) spatial frequency is shown binocularly at systematically varied orientations, uptake in parafoveal striate cortex is highest between the cytochrome oxidase blobs (that is, in the interblobs) in layers 1, 2, and 3. In layers 4B, 5, and 6, where the cytochrome oxidase blobs are faint or absent, DG uptake is highest in a periodic pattern that lies in register with the interblobs of layers 2 + 3. When the grating is, instead, of relatively low (1-1.5 cycles/deg) spatial frequency, DG uptake is highest in the blobs, in the blob-aligned portions of layers 1-4B, and in the lower-layer blobs as well. These variations in DG topography are confirmed in stimulus comparisons within a single hemisphere. Presumably, this shift in functional topography within the extra-granular layer is the primate homolog of "spatial frequency columns" shown earlier in the cat (Tootell et al., 1981; Silverman, 1984). In the well-differentiated architecture of primate striate cortex, laminar differences produced by high- versus low-spatial-frequency gratings are visible as well. Gratings of very high spatial frequency produce much higher uptake in 4Cb (which receives input from the parvocellular LGN layers) than in 4Ca (which gets its input from the magnocellular LGN layers). Gratings of low spatial frequency produce the converse result. Presumably, cells in the magnocellular LGN layers and/or in the magnocellular-dominated layer 4Ca have lower average spatial frequency tuning (larger receptive fields) than their counterparts in the parvocellular LGN and/or in striate layer 4Cb. The DG patterns produced by various spatial frequencies also vary with eccentricity, in a manner consistent with known, eccentricity-dependent variations of receptive-field size and spatial frequency tuning. Thus, gratings of a "middle"-spatial-frequency range (4-5 cycles/deg) produce high uptake in the blobs near the foveal representation and high uptake in the interblobs at more peripheral eccentricities, including 5 degrees. This shift in DG topography also includes the transition zone near 3 degrees, where the level of stimulus-driven uptake is as high in the blob regions as it is in interblob regions. Variations in uptake between layers 4Ca and 4Cb, as a function of eccentricity, shift in parallel with the changes in the upper-layer topography.

A series of experiments was carried out using 14C-2-deoxy-d-glucose (DG) in order to examine the functional architecture of macaque striate (primary visual) cortex. This paper describes the results of experiments on uptake during various baseline (or reference) conditions of visual stimulation (described below), and on differences in the functional architecture following monocular versus binocular viewing conditions. In binocular “baseline” experiments, monkeys were stimulated either (1) in the dark, (2) with a diffuse gray screen, or (3) with a very general visual stimulus composed of gratings of varied orientation and spatial frequency. In all of these conditions, DG uptake was found to be topographically uniform within all layers of parafoveal striate cortex. In monocular experiments that were otherwise similar, uptake was topographically uniform within the full extent of the eye dominance strip, in all layers. Certain other visual stimuli produce high uptake in the blobs, and still another set of visual stimuli (including high-spatial-frequency gratings) produce highest uptake between the blobs at parafoveal eccentricities, even in an unanesthetized, unparalyzed monkey. Eye movements per se had no obvious effect on striate DG uptake. Endogenous uptake in the blobs (relative to that in the interblobs) appears higher in the squirrel monkey than in the macaque. The pattern of DG uptake produced by binocular viewing was found to deviate in a number of ways from that expected by linearly summing the component monocular DG patterns. One of the most interesting deviations was an enhancement of the representation of visual field borders between stimuli differing from each other in texture, orientation, direction, etc. This “border enhancement” was confined to striate layers 1–3 (not appearing in any of the striate input layers), and it only appeared following binocular, but not monocular, viewing conditions. The border enhancement may be related to a suppression of DG uptake that occurs during binocular viewing conditions in layers 2 + 3 (and perhaps layers 1 and 4B), but not in layers 4Ca, 4Cb, 5 or 6. Another major class of binocular interaction was a spread of neural activity into the “unstimulated” ocular dominance strips following monocular stimulation. Such an effect was prominent in striate layer 4Ca, but it did not occur in layer 4Cb. This “binocular” spread of DG uptake into the inappropriate eye dominance strip in 4Ca may be related to the appearance of orientation tuning and orientation columns in that layer. No DG effects were seen that depended on the absolute disparity of visual stimuli in macaque striate cortex.

Objective To evaluate the safety of radiofrequency (RF) central temperatures reaching up to 105°C during 12 min of ablation; rectal temperature remained at energy delivered interstitially in patients with prostate cancer scheduled for radical prostatectomy and to <38°C. There were no complications. Macroscopic examination showed well-demarcated lesions includcorrelate the proposed theoretical lesion size with the pathological findings.ing the prostatic capsule, up to 2.2×1.5×4.5 cm. With monopolar energy, the observed lesion size was Patients and methods Radiofrequency interstitial tumour ablation (RITA) was performed in 15 patients comparable to the predicted 2×2×2 cm lesion, while with bipolar energy, lesion size was related to interwith localized prostate cancer before radical surgery. RF energy was delivered to the prostate by active needle distance and uncovered needle length. Microscopic examination showed clearly delineated needle electrodes (monopolar or bipolar) placed transperineally under transrectal ultrasonography guidlesions both with NADPH (in prostates immediately removed after surgery) and H&E (at 1 week after RITA) ance. Needle electrodes were used with diCerent configurations and in some cases were covered by staining. The lesion size observed on pathological analysis correlated with the predicted lesion size. In retractable shields to vary the length and circumference of the thermal lesions created. In eight patients, one patient, no residual cancer was found in the specimen. In the patient whose entire prostate was the procedure was performed immediately before radical prostatectomy, in six RITA was performed under targeted and followed by serial PSA measurements, the latter were undetectable at 3 months of follow-up. spinal anaesthesia 1 week before surgery and in one patient, no surgery was performed but the patient was Conclusion Transperineally delivered RF energy is capable of safely creating extensive coagulative necrotic followed by serial determinations of prostate specific antigen (PSA). At least two lesions were created in lesions in prostate cancer tissue, in a reproducible and controlled manner. The results presented here provide each prostate, including both capsule and peripheral zones. NADPH and haematoxylin & eosin (H&E) stainbasic information for the potential future application of this form of energy for localized prostate cancer. ing were used to assess the extent of the necrotic lesion in the radical prostatectomy specimen.Keywords Prostate cancer, radiofrequency, tumour ablation, transrectal ultrasonography Results The mean energy delivered was 10.5 kJ, with publicised in recent studies, can only be oCered to

Clinical management policies are meant to lead to the delivery of better health care. However, as we demonstrate in this review, having an oral or written venous thromboembolism prophylaxis policy does not necessarily lead to the majority of general surgical inpatients receiving the appropriate prophylaxis. We discovered, through prospective clinical audit, that for a clinical policy to be effective in delivering the appropriate health care, it must be repeatedly scrutinized and implemented in the correct manner. Only after several rounds of the audit cycle were we able to achieve the deliverance of venous thromboembolism prophylaxis to the majority of general surgical patients on our unit. This has wider implications, not just for the implementation of a venous thromboembolism prophylaxis policy, but also for all clinical management policies, and illustrates the importance of clinical audit in clinical practice.