Short Proofs Are Hard to Find

We obtain a streamlined proof of an important result by Alekhnovich and Razborov [Michael Alekhnovich and Alexander A. Razborov, 2008], showing that it is hard to automatize both tree-like and general Resolution. Under a different assumption than [Michael Alekhnovich and Alexander A. Razborov, 2008], our simplified proof gives improved bounds: we show under ETH that these proof systems are not automatizable in time n^f(n), whenever f(n) = o(log^{1/7 - epsilon} log n) for any epsilon > 0. Previously non-automatizability was only known for f(n) = O(1). Our proof also extends fairly straightforwardly to prove similar hardness results for PCR and Res(r)

Neuronal imaging with ultrahigh dynamic range multiphoton microscopy

Multiphoton microscopes are hampered by limited dynamic range, preventing weak sample features from being detected in the presence of strong features, or preventing the capture of unpredictable bursts in sample strength. We present a digital electronic add-on technique that vastly improves the dynamic range of a multiphoton microscope while limiting potential photodamage. The add-on provides real-time negative feedback to regulate the laser power delivered to the sample, and a log representation of the sample strength to accommodate ultrahigh dynamic range without loss of information. No microscope hardware modifications are required, making the technique readily compatible with commercial instruments. Benefits are shown in both structural and in-vivo functional mouse brain imaging applications.R21 EY027549 - NEI NIH HH

Simultaneous multiplane imaging with reverberation multiphoton microscopy

Multiphoton microscopy (MPM) has gained enormous popularity over the years for its capacity to provide high resolution images from deep within scattering samples1. However, MPM is generally based on single-point laser-focus scanning, which is intrinsically slow. While imaging speeds as fast as video rate have become routine for 2D planar imaging, such speeds have so far been unattainable for 3D volumetric imaging without severely compromising microscope performance. We demonstrate here 3D volumetric (multiplane) imaging at the same speed as 2D planar (single plane) imaging, with minimal compromise in performance. Specifically, multiple planes are acquired by near-instantaneous axial scanning while maintaining 3D micron-scale resolution. Our technique, called reverberation MPM, is well adapted for large-scale imaging in scattering media with low repetition-rate lasers, and can be implemented with conventional MPM as a simple add-on.Accepted manuscrip

Lifting with Sunflowers

Query-to-communication lifting theorems translate lower bounds on query complexity to lower bounds for the corresponding communication model. In this paper, we give a simplified proof of deterministic lifting (in both the tree-like and dag-like settings). Our proof uses elementary counting together with a novel connection to the sunflower lemma. In addition to a simplified proof, our approach opens up a new avenue of attack towards proving lifting theorems with improved gadget size - one of the main challenges in the area. Focusing on one of the most widely used gadgets - the index gadget - existing lifting techniques are known to require at least a quadratic gadget size. Our new approach combined with robust sunflower lemmas allows us to reduce the gadget size to near linear. We conjecture that it can be further improved to polylogarithmic, similar to the known bounds for the corresponding robust sunflower lemmas

Ancient xenocrystic zircon in young volcanic rocks of the southern Lesser Antilles island arc

The Lesser Antilles arc is one of the best global examples in which to examine the effects of the involvement of subducted sediment and crustal assimilation in the generation of arc crust. Most of the zircon recovered in our study of igneous and volcaniclastic rocks from Grenada and Carriacou (part of the Grenadines chain) is younger than 2 Ma. Within some late Paleogene to Neogene (~ 34–0.2 Ma) lavas and volcaniclastic sediments however, there are Paleozoic to Paleoarchean (~ 250–3469 Ma) xenocrysts, and Late Jurassic to Precambrian zircon (~ 158–2667 Ma) are found in beach and river sands. The trace element characteristics of zircon clearly differentiate between different types of magmas generated in the southern Lesser Antilles through time. The zircon population from the younger arc (Miocene, ~ 22–19 Ma, to Present) has minor negative Eu anomalies, well-defined positive Ce anomalies, and a marked enrichment in heavy rare earth elements (HREE), consistent with crystallization from very oxidized magmas in which Eu2 + was in low abundance. In contrast, zircon from the older arc (Eocene to mid-Oligocene, ~ 30–28 Ma) has two different REE patterns: 1) slight enrichment in the light (L)REE, small to absent Ce anomalies, and negative Eu anomalies and 2) enriched High (H)REE, positive Ce anomalies and negative Eu anomalies (a similar pattern is observed in the xenocrystic zircon population). The combination of positive Ce and negative Eu anomalies in the zircon population of the older arc indicates crystallization from magmas that were variably, but considerably less oxidized than those of the younger arc. All the igneous zircon has positive εHf(t), reflecting derivation from a predominantly juvenile mantle source. However, the εHf(t) values vary significantly within samples, reflecting considerable Hf isotopic heterogeneity in the source. The presence of xenocrystic zircon in the southern Lesser Antilles is evidence for the assimilation of intra-arc crustal sediments and/or the recycling and incorporation of sediments into the magma sources in the mantle wedge. Most likely however, primitive magmas stalling and fractionating during their ascent through the Antilles crust entrained ancient zircon. This is evidence by the geochemistry of the study samples, which is inconsistent with any involvement of partially melted subducted sediment. Paleogeographic reconstructions show that the old zircon could derive from distant regions such as the Eastern Andean Cordillera of Colombia, the Merida Andes, and the northern Venezuela coastal ranges, transported for example by the Proto-Maracaibo River precursor of the Orinoco River.This study was supported by Deutsche Forschungsgemeinschaft (DFG) grants KR590/85-1 to AK and RO4174/2-1 to YRA, and Spanish MINECO grants CGL2015-65824 and CGL2012-36263 and University of Granada research program (CIC) to AGC and CLC. This research also received support from the SYNTHESYS Project (http://www.synthesys.info/) which is financed by the European Community Research Infrastructure Action under the FP7 “Capacities” Program, the Intra-University Research Support Program of Mainz University (Universitätsinterne Forschungsförderung (FoFö)

"It doesn't do any harm, but patients feel better": a qualitative exploratory study on gastroenterologists' perspectives on the role of antidepressants in inflammatory bowel disease

Background: Interest in psychological factors in patients with inflammatory bowel disease (IBD) has increased in recent years. It has even been proposed that treating psychological co-morbidities with antidepressants may control disease activity and improve quality of life. Despite this, there is no data on gastroenterologists' attitudes to, and experiences with, antidepressant therapy in patients with IBD. Methods: We conducted semi-structured interviews with 18 gastroenterologists associated with metropolitan teaching hospitals. Qualitative content analysis was used to examine their responses. Results: Seventy-eight percent of gastroenterologists had treated IBD patients with antidepressants for pain, depression and/or anxiety, and insomnia. Antidepressants were reported to be useful in improving psychosocial well-being, quality of life, and self-management of the disease by patients. However, in this group of gastroenterologists, there appears to be skepticism towards psychological disorders themselves or antidepressant therapy having a central role in either the causation of IBD or its clinical course. Nevertheless, these gastroenterologists were receptive to the idea of conducting a trial of the role of antidepressants in IBD. Conclusion: While the majority of specialists have treated IBD patients with antidepressants, there is considerable skepticism with regard to efficacy of antidepressive therapy or the role of psychological factors in the outcome of IBD patients.Antonina A Mikocka-Walus, Deborah A Turnbull, Nicole T Moulding, Ian G Wilson, Jane M Andrews and Gerald J Holtman

Does psychological status influence clinical outcomes in patients with inflammatory bowel disease (IBD) and other chronic gastroenterological diseases: An observational cohort prospective study

Background: Whether there is a temporal relationship between psychological problems and clinical outcomes in patients with diseases of the digestive tract has not been widely researched. Thus, our aims were 1) To observe and compare prospectively clinical outcomes in relation to psychological co-morbidity in patients with inflammatory bowel disease (IBD), irritable bowel syndrome (IBS) and chronic hepatitis C (HCV) and, 2) To test the hypothesis that patients with psychological co-morbidities are less likely to have a satisfactory response to standard treatment at 12 months. Methods: Overall, 139 patients were enrolled in this observational cohort prospective study. Over the ensuing year, physical and psychological measures were made at baseline and after 12 months (HADS, SCL90, SF-12 and disease activity measures). A logistic regression was conducted to observe any relationship between baseline characteristics and patients' clinical outcomes after 12 months. Results: Overall, there was no relationship between psychological status and quality of life at baseline and relapse at 12 months (p > 0.05). However, patients with inactive disease at baseline were at lower risk of relapse after 12 months (OR = 0.046, CI: 0.012–0.178). No significant relationship was found between psychological problems such as depression/anxiety and a total number of relapses in the IBD group. However, interestingly, patients with an active disease at baseline tended to have a greater number of relapses (OR = 3.07, CI: 1.650–5.738) and CD participants were found at lower risk of relapse than UC participants (OR = 0.382, CI: 0.198–0.736). Conclusion: In contrast to previous investigations, this study suggests that there is no temporal relationship between psychological problems at baseline and clinical outcomes over time. Longer and larger prospective studies are needed to better understand this result.Antonina A Mikocka-Walus, Deborah A Turnbull, Nicole T Moulding, Ian G Wilson, Gerald J Holtmann and Jane M Andrew

The impact of laxative use upon symptoms in patients with proven slow transit constipation

<p>Abstract</p> <p>Background</p> <p>Constipation severity is often defined by symptoms including feelings of complete evacuation, straining, stool frequency and consistency. These descriptors are mostly obtained in the absence of laxative use. For many constipated patients laxative usage is ubiquitous and long standing. Our aim was to determine the impact of laxative use upon the stereotypic constipation descriptors.</p> <p>Methods</p> <p>Patients with confirmed slow transit constipation completed 3-week stool diaries, detailing stool frequency and form, straining, laxative use and pain and bloating scores. Each diary day was classified as being under laxative affect (laxative affected days) or not (laxative unaffected days). Unconditional logistic regression was used to assess the affects of laxatives on constipation symptoms.</p> <p>Results</p> <p>Ninety four patients with scintigraphically confirmed slow transit constipation were enrolled in the study. These patients reported a stool frequency of 5.6 ± 4.3 bowel motions/week, only 21 patients reported <3 bowel motions/week. Similarly, 21 patients reported a predominant hard stool at defecation. The majority (90%) of patients reported regular straining. A regular feeling of complete evacuation was reported in just 7 patients. Daily pain and/or bloating were reported by 92% of patients. When compared with laxative unaffected days, on the laxative affected days patients had a higher stool frequency (OR 2.23; <it>P </it><0.001) and were more likely to report loose stools (OR 1.64; <it>P </it><0.009). Laxatives did not increase the number of bowel actions associated with a feeling of complete evacuation. Laxative use had no affect upon straining, pain or bloating scores</p> <p>Conclusions</p> <p>The reporting of frequent and loose stools with abdominal pain and/or bloating is common in patients with slow transit constipation. While laxative use is a significant contributor to altering stool frequency and form, laxatives have no apparent affect on pain or bloating or upon a patients feeling of complete evacuation. These factors need to be taken into account when using constipation symptoms to define this population.</p