Identifying a neuroanatomical signature of schizophrenia, reproducible across sites and stages, using machine learning with structured sparsity.

OBJECTIVE: Structural MRI (sMRI) increasingly offers insight into abnormalities inherent to schizophrenia. Previous machine learning applications suggest that individual classification is feasible and reliable and, however, is focused on the predictive performance of the clinical status in cross-sectional designs, which has limited biological perspectives. Moreover, most studies depend on relatively small cohorts or single recruiting site. Finally, no study controlled for disease stage or medication's effect. These elements cast doubt on previous findings' reproducibility. METHOD: We propose a machine learning algorithm that provides an interpretable brain signature. Using large datasets collected from 4 sites (276 schizophrenia patients, 330 controls), we assessed cross-site prediction reproducibility and associated predictive signature. For the first time, we evaluated the predictive signature regarding medication and illness duration using an independent dataset of first-episode patients. RESULTS: Machine learning classifiers based on neuroanatomical features yield significant intersite prediction accuracies (72%) together with an excellent predictive signature stability. This signature provides a neural score significantly correlated with symptom severity and the extent of cognitive impairments. Moreover, this signature demonstrates its efficiency on first-episode psychosis patients (73% accuracy). CONCLUSION: These results highlight the existence of a common neuroanatomical signature for schizophrenia, shared by a majority of patients even from an early stage of the disorder.

Near infrared and skin impedance spectroscopy - a possible support in the diagnostic process of skin tumours in primary health care.

BACKGROUND/PURPOSE: The global incidence of skin cancer has increased drastically in recent decades, especially in Australia and Northern Europe. Early detection is crucial for good prognosis and high survival rates. In general, primary care physicians have considerably lower sensitivity and specificity rates for detection of skin cancer, compared to dermatologists. A probable main reason for this is that current diagnostic tools are subjective in nature, and therefore diagnostic skills highly depend on experience. Illustratively, in Sweden, approximately 155 500 benign skin lesions are excised unnecessarily every year. An objective instrument, added to the clinical examination, might improve the diagnostic accuracy, and thus promote earlier detection of malignant skin tumours, as well as reduce medical costs associated with unnecessary biopsies and excisions. The general aim of this study was to investigate the usefulness of the combination of near infrared (NIR) and skin impedance spectroscopy as a supportive tool in the diagnosis and evaluation of skin tumours in primary health care. METHODS: Near infrared and skin impedance data were collected by performing measurements on suspect malignant, premalignant and benign tumours in the skin of patients seeking primary health care for skin tumour evaluation. The obtained data were analysed using multivariate analysis and compared with the diagnosis received by the conventional diagnostic process. RESULTS: The observed sensitivity and specificity rates were both 100%, when discriminating malignant and premalignant skin tumours from benign skin tumours, and the observed sensitivity and specificity for separating malignant skin tumours from premalignant and benign skin tumours were also 100%, respectively. CONCLUSION: The results of this study indicate that the NIR and skin impedance spectroscopy may be a useful supportive tool for the general practitioner in the diagnosis and evaluation of skin tumours in primary health care, as a complement to the visual assessment.

Preliminary evaluation of dorsal muscle activity during resisted cervical extension in patients with longstanding pain and disability following anterior cervical decompression and fusion surgery.

OBJECTIVES: To compare mechanical activity (deformation and deformation rate) of the dorsal neck muscles between individuals with longstanding symptoms after anterior cervical decompression and fusion (ACDF) surgery and healthy controls. DESIGN: Preliminary cross-sectional study. SETTING: Neurosurgery clinic. PARTICIPANTS: Ten individuals {mean age 60 [standard deviation (SD) 7.1]} who had undergone ACDF surgery 10 to 13 years previously and 10 healthy age- and sex-matched controls. MAIN OUTCOMES: Mechanical activity of the different layers of dorsal neck muscles, measured at the C4 segment using ultrasonography (speckle tracking analysis) during a standardised, resisted cervical extension task. RESULTS: A significant group×muscle interaction was found for muscle deformation (P<0.03) but not for deformation rate (P>0.79). The ACDF group showed significantly less deformation of the semispinalis capitis muscle during the extension task compared with the control group [mean 3.12 (SD 2.06) and 6.64 (SD 4.17), respectively; mean difference 3.34 (95% confidence interval -0.54 to 7.21)]. CONCLUSIONS: As the semispinalis capitis muscle is a powerful neck extensor, the finding of altered activation following ACDF surgery lends support to the inclusion of exercise to train neck muscle performance in the management of these patients.

Adrenergic innervation of aortic patch-grafts in rats.

The regeneration of vascular adrenergic nerves was studied using the glyoxylic acid-induced fluorescence method for the specific demonstration of adrenergic nerves in syngeneic patch-grafts of the right atrium of the heart, vena cava and glutaraldehyde-treated vena cava transplanted into the abdominal aorta of the rat. Glutaraldehyde-treated segments of the supradiaphragmatic inferior vena cava were transplanted into the abdominal aorta of rats as well. At the end of the observation period of 24 weeks limited, patchy and defective innervation was observed in the syngeneic vena cava and atrial patches. No adrenergic nerves were found in the glutaraldehyde-treated vein patch-grafts or vein grafts. Owing to the very poor innervation of atrial and venous patch-grafts the results are not entirely in agreement with the target organ concept of adrenergic nerve regeneration. In this study the suture line around the patch graft probably hampers regeneration of vascular adrenergic nerves in the patches.

Innervation of syngeneic vein grafts in the rat. The regeneration of adrenergic nerves.

Regeneration of adrenergic nerves was studied sequentially in segments of the supradiaphragmatic inferior vena cava transplanted from one rat into the abdominal aorta of another of the same inbred strain. Nontransplanted vein segments were examined as controls. The adrenergic nerves were demonstrated by using the glyoxylic acid-induced fluorescence method and the formaldehyde-induced fluorescence method for the demonstration of cathecholamines. A total of 16 syngeneic grafts were examined 3, 5, 8, 16, 27, and 32 weeks after transplantation. Three additional grafts were wrapped inside a silicone tube during the operation to prevent regeneration of nerves from the surroundings. These rats were then killed 8 weeks after the operation. In the control specimens the supradiaphragmatic inferior vena cava was innervated with a rather dense plexus of adrenergic nerves showing varicosities. No nerves were seen in the 3-week-old grafts. In the 5-week-old grafts some sparsely distributed solitary nerve fibres were seen. In the 8-week-old grafts sparsely distributed regenerated nerves reinnervating the vasa vasorum and nerve plexa were observed. The 16-, 27-, and 32-week-old grafts showed rather poorly innervated areas and areas where the nerve plexus was dense. One graft showed very dense reinnervation with morphologically abnormal adrenergic nerves forming "droplet fibers" and showing dense accumulations of catecholamines. The grafts surrounded with silicone tubes had no adrenergic nerves and showed only some regenerated nerves crossing the suture line. The results of the present study indicated that syngeneic inferior vena cava transplanted into the abdominal aorta will be reinnervated with adrenergic nerves. The pattern of the nerve regeneration remains incomplete and patchy.

Innervation of syngeneic vein grafts in the rat. The regeneration of cholinesterase positive nerves.

The regeneration of cholinesterase positive nerves into segments of the supradiaphragmatic inferior vena cava transplanted from one rat into the abdominal aorta of another rat of the same inbred strain and sex were studied, using a histochemical thiocholine method for the demonstration of cholinesterase. Iso-OMPA and BW-284 C 51 were used as inhibitors for nonspecific cholinesterase (nsChE) and acetylcholinesterase (AChE), respectively. A total of 12 grafts were examined 3, 5, 8, 16, 27 and 32 weeks after transplantation. One single regenerating nsChE reactive nerve was seen near the suture line in a 3-week-old graft. Some solitary regenerating nerves were regularly seen in the grafts at 5 weeks. Eight weeks after grafting some solitary sparsely distributed nerves were found in the outer layers of the graft. In the 16-, 27-, and 32-week-old grafts, nsChE reactive nerves and small nerve bundles were running either solitary or forming nerve plexa in addition to nerves in the vicinity of vasa vasorum. These regenerated nsChE reactive nerves are probably vasomotor in nature. The AChE reaction showed a clear activity in the intimal layer of the grafted veins. No AChE reactive nerves were seen in the 3-, 5-, and 8-week-old grafts. Only occasional AChE positive nerves were observed 16, 28 and 32 weeks after transplantation. These nerves are probably sympathetic cholinergic nerves.