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Individuals with attention-deficit/hyperactivity disorder (ADHD) have difficulties navigating dynamic everyday situations that contain multiple sensory inputs that need to either be attended to or ignored. As conventional experimental tasks lack this type of everyday complexity, we administered a film-based multi-talker condition with auditory distractors in the background. ADHD-related aberrant brain responses to this naturalistic stimulus were identified using intersubject correlations (ISCs) in functional magnetic resonance imaging (fMRI) data collected from 51 adults with ADHD and 29 healthy controls. A novel permutation-based approach introducing studentized statistics and subject-wise voxel-level null-distributions revealed that several areas in cerebral attention networks and sensory cortices were desynchronized in participants with ADHD (n = 20) relative to healthy controls (n = 20). Specifically, desynchronization of the posterior parietal cortex occurred when irrelevant speech or music was presented in the background, but not when irrelevant white noise was presented, or when there were no distractors. We also show regionally distinct ISC signatures for inattention and impulsivity. Finally, post-scan recall of the film contents was associated with stronger ISCs in the default-mode network for the ADHD and in the dorsal attention network for healthy controls. The present study shows that ISCs can further our understanding of how a complex environment influences brain states in ADHD.

The first US Food and Drug Administration (FDA)- and EMA-approved oncolytic virus has been available since 2015. However, there are no markers available that would predict benefit for the individual patient. During 2007–2012, we treated 290 patients with advanced chemotherapy-refractory cancers, using 10 different oncolytic adenoviruses. Treatments were given in a Finnish Medicines Agency (FIMEA)-regulated individualized patient treatment program (the Advanced Therapy Access Program [ATAP]), which required long-term follow-up of patients, which is presented here. Focusing on the longest surviving patients, some key clinical and biological features are presented as “oncograms.” Some key attributes that could be captured in the oncogram are suggested to predict treatment response and survival after oncolytic adenovirus treatment. The oncogram includes immunological laboratory parameters assessed in peripheral blood (leukocytes, neutrophil-to-lymphocyte ratio, interleukin-8 [IL-8], HMGB1, anti-viral neutralizing antibody status), features of the patient (gender, performance status), tumor features (histological tumor type, tumor load, region of metastases), and oncolytic virus-specific features (arming of the virus). The retrospective approach used here facilitates verification in a prospective controlled trial setting. To our knowledge, the oncogram is the first holistic attempt to identify the patients most likely to benefit from adenoviral oncolytic virotherapy. Keywords: oncolytic adenovirus, oncolytic virotherapy, immunotherapy, cancer, immunostimulation, anti-cancer, adenovirus, oncoimmunology, immunogram, oncogram

Hydrocephalic patients with abdominal pathologies often need a ventriculo-atrial (VA) shunt placement. Cut-down on the internal jugular vein has historically been used to insert a VA shunt. This technique is more time consuming and has greater complications. Less invasive methods, such as ultrasound-guided percutaneous VA shunt placement provides greater comfort for surgeon, is more rapid, and has fewer complications. However, this technique has not been demonstrated on video. Here we demonstrate ultrasound-guided and ECG-aided VA shunt catheter placement in a 70-year-old patient with normal pressure hydrocephalus. The internal jugular vein is punctured under ultrasound guidance with an 18-gauge needle. A guidewire is introduced through the needle, the needle is removed, and a small skin incision is placed at the entry point of the guidewire. A skin dilator with a sheath introducer is advanced to the vein using the guidewire and the guidewire is thereafter removed. An atrial shunt catheter (e.g. Codman® Medos® Atrial catheter) filled with sterile water is inserted through the sheath. The sheath is removed and a syringe filled with sterile aqua is connected to the catheter with a metal tip. The ECG connection of the right upper limb is connected to the tip of syringe to adjust for the optimal depth of the catheter under ECG guidance (point of highest p-wave amplitude). The catheter is clamped and tunneled to reach the site for the valve on the scalp. The ventricle catheter is placed at the Kocher point and connected to the valve (Video 1). Conclusion: Ultrasound-guided VA shunt placement is safe, comfortable, rapid, and has a reduced rate of complications. Keywords: Ventriculo-atrial shunt placement, Surgery, Technical aspects, Video demonstration

Natural tropism to the liver is a major obstacle in systemic delivery of adenoviruses in cancer gene therapy. Adenovirus binding to soluble coagulation factors and to cellular heparan sulphate proteoglycans via the fiber shaft KKTK domain are suggested to cause liver tropism. Serotype 5 adenovirus constructs with mutated KKTK regions exhibit liver detargeting, but they also transduce tumors less efficiently, possibly due to altered fiber conformation. We constructed Ad5/3lucS*, a 5/3 chimeric adenovirus with a mutated KKTK region. The fiber knob swap was hypothesized to facilitate tumor transduction. This construct was studied with or without additional coagulation factor ablation. Ad5/3lucS* exhibited significantly reduced transduction of human hepatic cells in vitro and mouse livers in vivo. Combination of coagulation factor ablation by warfarinization to Ad5/3lucS* seemed to further enhance liver detargeting. Cancer cell transduction by Ad5/3lucS* was retained in vitro. In vivo, viral particle accumulation in M4A4-LM3 xenograft tumors was comparable to controls, but Ad5/3lucS* transgene expression was nearly abolished. Coagulation factor ablation did not affect tumor transduction. These studies set the stage for further investigations into the effects of the KKTK mutation and coagulation factor ablation in the context of 5/3 serotype chimerism. Of note, the putative disconnect between tumor transduction and transgene expression could prove useful in further understanding of adenovirus biology.