Saturation diving is an occupation that involves prolonged exposure to a confined, hyperoxic, hyperbaric environment. The unique and extreme environment is thought to result in disruption to physiological and metabolic homeostasis, which may impact human health and performance. Appropriate nutritional intake has the potential to alleviate and/or support many of these physiological and metabolic concerns, whilst enhancing health and performance in saturation divers. Therefore, the purpose of this review is to identify the physiological and practical challenges of saturation diving and consequently provide evidence-based nutritional recommendations for saturation divers to promote health and performance within this challenging environment. Saturation diving has a high-energy demand, with an energy intake of between 44 and 52 kcal/kg body mass per day recommended, dependent on intensity and duration of underwater activity. The macronutrient composition of dietary intake is in accordance with the current Institute of Medicine guidelines at 45–65 % and 20–35 % of total energy intake for carbohydrate and fat intake, respectively. A minimum daily protein intake of 1.3 g/kg body mass is recommended to facilitate body composition maintenance. Macronutrient intake between individuals should, however, be dictated by personal preference to support the attainment of an energy balance. A varied diet high in fruit and vegetables is highly recommended for the provision of sufficient micronutrients to support physiological processes, such as vitamin B12 and folate intake to facilitate red blood cell production. Antioxidants, such as vitamin C and E, are also recommended to reduce oxidised molecules, e.g. free radicals, whilst selenium and zinc intake may be beneficial to reinforce endogenous antioxidant reserves. In addition, tailored hydration and carbohydrate fueling strategies for underwater work are also advised. Saturation diving is a unique and challenging occupation, which exposes the body to a range of extreme environmental and physiological stressors –3. This The hyperbaric conditions associated with saturation diving represents the linear relationship between increasing atmospheric pressure and sea depth . ChronicAppropriate nutritional strategies have the potential to alleviate many of these physiological concerns; however, limited guidance related to nutritional recommendations for this population is currently available. The purpose of this review, therefore, is to explore the physiological and practical challenges associated with this occupation. These challenges will then be considered within the context of current nutrition guidelines for general and athletic populations, in order to establish specific nutritional recommendations to optimise health and performance of individuals in this unique and challenging occupation. It is beyond the scope of this review to provide an in-depth review of the physical characteristics or physiological and pathophysiological concerns of saturation diving. Readers are directed to alternative reviews for such information –3.2). Typically, the gas mixtures used during a saturation dive comprise a combination of oxygen and helium and/or nitrogen. These latter two gases are known as inert gases, which are deemed to metabolically inactive and thereby purported to have a minimal effect on physiological systems [Saturation diving practices differ based on location and sector but can typically extend for periods of up to twenty-eight days within a hyperbaric, mixed gas atmosphere. The compressive forces on the gaseous molecules from hyperbaria result in increased density of ambient air and increased partial pressure of oxygen , which can cause muscle and joint pain, nausea and paralysis. Manifestations of DCS occur via the formation of microbubbles along with associated inflammatory and immunological challenges . In ordeThe effect of dietary intake on metabolic and physiological processes is vast, with the application of personalised nutritional strategies deemed to be most effective in promoting performance and health. Accordingly, the current review aims to synthesise the available literature related to the physiological responses to saturation diving, and to consider these in relation to commonly accepted nutritional principles –22. RecoConsistent reports of body mass loss while in saturation , 13, 23 Paciorek  calculat2 and VCo2 data provided during submaximal exercise allowed calculation of fat and carbohydrate oxidation using stoichiometric equations [Research regarding the utilisation of metabolic substrates at rest and during physical activity during hyperbaria or hyperoxia is sparse , 26, 27,quations . The anaquations . In addiquations . TherefoThe information presented on fuel utilisation under hyperoxia demonstrates a trend towards increased fat oxidation, but no study has directly assessed fuel use during an extended saturation dive either in the chamber or during an underwater excursion. Therefore, the current research may not be considered strong enough to provide recommendations that greatly deviate from general guidelines proposed by the Institute of Medicine (IOM) . CurrentCurrent carbohydrate recommendations for the general population are between 45 and 65 % of total calorie intake . To alloKnowledge of protein metabolism is important to provide guidelines on appropriate protein intakes, due to the implications on health and body composition , 32. A sIt appears appropriate to propose that under the unique environmental and physiological challenges, protein intake for saturation divers should be above the recommended daily allowance for the general population, which is currently 0.8 g/kg BM a day. An appropriate recommendation for this population would be a minimum of 1.3 g/kg BM a day, aligning with current recommendations to maximise muscle protein synthesis . It may Micronutrients are involved in various physiological functions in the body and are essential to the overall health of an individual. It is likely that if the higher energy intake described previously is achieved through a balanced and varied diet then the current IOM guidelines for micronutrient intakes will be met . For satBrubakk et al.  identifi−1 by day 12 (from 92 ± 23 to 81 ± 18 nmol L−1) in a sample of six divers. If this trends were to continue over a full 28 day dive, concentrations could drop by more than 20 nmol L−1. Smith et al. [Vitamin D is unique compared to other essential vitamins, predominantly as the main source is through ultraviolet B (UVB) radiation from sunlight as opposed to dietary intake . Accordih et al.  conducte−1, the current IOM threshold for vitamin D adequacy [Due to the difficulty of obtaining sufficient vitamin D through dietary intake alone , along wadequacy . We recoadequacy , so we sadequacy  whilst 4adequacy . TherefoThe term oxidative stress refers to a state caused by the generation of oxidised molecules such as reactive oxygen species (ROS) and free radicals that are greater than the ability of the body’s antioxidant system to reduce them, and may result in damage to cellular proteins, lipids and DNA. Research has implicated this imbalance between ROS and antioxidant reserves with the pathogenesis of various disorders, including cardiovascular and neurodegenerative diseases, diabetes and several types of cancer –48. WhilExogenous antioxidants obtained through a healthy diet are associated with low levels of oxidative stress. A number of randomised controlled trials have shown that fruit and vegetable intake, which are antioxidant rich, can reduce markers of oxidative stress in healthy individuals –52. TherHaemoglobin concentrations throughout the course of a saturation dive have consistently been shown to decline , 55, 56.Vitamin B12 and folate are involved in the production red blood cells  and are Iron also has an important role in haematological processes. However, iron has been reported to accumulate within the body during saturation, which is likely to be due to the decline in red blood cell content . ExcessiMaintenance of fluid and electrolyte homeostasis is required to ensure usual physiological function, due to the wide range of functions which water fulfils within human metabolism . Hypohydp < 0.05), a 54 % increase in sodium excretion  and a 32 % reduction in urine osmolality  during a 7-day simulated saturation dive. Furthermore, the increased sodium loss [The primary factor that may challenge fluid homeostasis within the saturation chamber is hyperbaric diuresis. This refers to an excess production of urine, which has been reported to occur under conditions of hyperbaric hyperoxia –6. Sagawium loss .In addition to the hydration challenges associated with the hyperbaric environment, underwater work periods may also compromise the body’s ability to maintain euhydration. Performing physically demanding work while immersed in water and wearing a hot water diving suit may create a state of thermal stress , which iThe ultimate goals of the hydration recommendations made are to encourage maintenance of in-chamber euhydration, and to ensure sufficient fluid replacement following lockout. Prescriptive recommendations related to hydration strategies are difficult due to the highly individual nature of the body’s response. In accordance with guidelines from the British Dietetics Association, a minimum of 2 L/day of water is recommended. This recommendation aligns with those provided for astronauts, a group who experience similar environmental challenges to saturation divers, including changes to atmospheric pressure, and confinement for prolonged periods of time.Given the large fluid losses reported during lockout, along with the limited opportunities to drink, more extensive hydration strategies may be required in order to counteract these factors. The primary pre-lockout goal should be to ensure that divers enter lockout in a euhydrated state, with the consumption of food and fluid containing sodium to be used prior to lockout to facilitate fluid retention , 71. Duel-arginine can be used as an alternative to increase NO production [The aspects highlighted within these guidelines have primarily focused on the role of nutrition on the health and performance of saturation divers. There is, however, emerging evidence to suggest that nutritional strategies may also enhance safety of divers during decompression. Administration of exogenous nitric oxide (NO) reduces microbubble formation after decompression  in diveroduction . NeverthIn addition to the physiological factors described above, there are also a number of practical challenges associated with saturation diving that may present barriers to achieving appropriate nutritional intake. Therefore, nutritional recommendations for this population should be cognisant of both physiological and practical considerations, thereby allowing greater opportunity to practice appropriate dietary strategies within this challenging environment. The greatest practical barriers to nutritional intake include shift patterns and food provision, lockout and food palatability. These areas will be discussed in more detail below, along with recommendations to facilitate nutritional intake to overcome practical barriers.Saturation divers are allocated 12 h shift patterns, during which they can be asked to enter lockout. This necessitates the adjustment of daily routines to the allocated time periods and may distort perception of normal night and day. It has been suggested that shift work  can impact upon the ability to maintain usual eating patterns, particularly if food choices are limited . At any During lockout saturation, divers are isolated from the main vessel for up to 8 h, 6 of which may involve underwater immersion and the completion of physically demanding tasks whilst wearing a hot water diving suit. Previously, divers had limited opportunity to refuel or rehydrate during lockout, although recent legislative changes stipulate a mandatory break if they are to be immersed for 4 h or longer, which may have a positive influence on ability to maintain fluid and energy balance during lockout. Simple steps can be taken to encourage dietary intake in this situation, for example, provision of energy dense snacks in the bell may encourage intake. These snacks can be consumed while the divers are being transported to and from the working depth or during the mandatory 30-min break mid-lockout. The use of a carbohydrate-based sports drink may be most appropriate for this situation as it can provide the energy, fluid and electrolytes that are required when working. Sport nutrition research has shown that the minimum rate of carbohydrate ingestion to elicit physical performance benefits is 16 g/h , which iThe timing of energy intake around lockout is also deemed pertinent. Increased energy availability has been suggested to have a considerable impact upon physical performance , more spAll food that enters the saturation chamber is compressed to the ambient pressure, which in certain instances appears to distort the perception of food palatability , 83. ThoPersonal communication between the authors and saturation divers has also revealed that appetite may be suppressed after an intense shift underwater. This phenomenon warrants scientific investigation; however, the theory is plausible as participation in physically demanding activities has been reported to transiently reduce hunger sensations , represeThis review aimed to provide nutritional recommendations for saturation divers based upon the physiological and practical challenges encountered by these individuals. The primary recommendations are summarised within Table


In this paper, we propose a novel 2D-to-3D video conversion method for 3D entertainment applications. 3D entertainment is getting more and more popular and can be found in many contexts, such as TV and home gaming equipment. 3D image sensors are a new method to produce stereoscopic video content conveniently and at a low cost, and can thus meet the urgent demand for 3D videos in the 3D entertaiment market. Generally, 2D image sensor and 2D-to-3D conversion chip can compose a 3D image sensor. Our study presents a novel 2D-to-3D video conversion algorithm which can be adopted in a 3D image sensor. In our algorithm, a depth map is generated by combining global depth gradient and local depth refinement for each frame of 2D video input. Global depth gradient is computed according to image type while local depth refinement is related to color information. As input 2D video content consists of a number of video shots, the proposed algorithm reuses the global depth gradient of frames within the same video shot to generate time-coherent depth maps. The experimental results prove that this novel method can adapt to different image types, reduce computational complexity and improve the temporal smoothness of generated 3D video. This technology has been used in various entertainment applications, such as movies, computer games, and animation. 3D entertainment is now becoming more and more popular and it will be the future trend in the field of entertainment. However, one of the challenges that has been faced in the field of 3D entertainment is the lack of 3D video content.The approach to obtain 3D video content requires professional stereoscopic camera containing two-view image sensors. However, professional equipment is cumbersome, expensive and difficult to operate . These lAs 2D image sensors are very common around us, making full use of an ordinary single 2D image sensor to generate 3D video content has broad prospects. It is challenging but feasible: a new method using a 2D image sensor plus a 2D-to-3D conversion function can be adopted to obtain 3D video contents. An ordinary 2D image sensor can be packeged together with a 2D-to-3D chip to create a 3D image sensor. Thus the 3D video contents can be easily generated through 3D image sensors and the cost of acquisition of 3D video content can be reduced by a large margin, which will greatly promote the development of 3D entertainment markets. In this paper, we propose a new 2D-to-3D conversion algorithm, which can be adopted in a 3D image sensor. The framework of 2D-to-3D video conversion is shown in et al. [et al. [et al. [In the process of 2D-to-3D video conversion, depth map generation is an essential procedure and the latter procedure is relatively fixed. 2D video has a lack of depth information compared with 3D video. Depth information can be depicted by a depth map, which is a gray-scale image whose value for the farthest pixel is 0 and the nearest pixel is 255. A depth map can be obtained from single monocular view through various depth cues including texture gradient, geometric perspective, focus/defocus, interposition, motion parallax, relative height or size and so on . A numbe [et al.  use threIn this paper, we present a novel algorithm to overcome the above shortcomings. The algorithm first detects whether the input frame belongs to a new video shot or not. If the frame belongs to a new video shot, the algorithm judges its image type and assigns a global depth gradient according to its image type. Three categories of image types are defined in our algorithm: landscape type, linear perspective type and normal type. An approach to generate global depth gradient for each image type is devised as well. If the frame does not belong to a new video shot, the global depth gradient of previous frame is reused. After the global depth gradient is obtained, it is refined by local depth information to generate the depth map. Cross bilateral filter and DIBR are then applied to produce the final depth map and 3D video. The innovations of our work can be summarized in the two following points:The algorithm can determine the image type of the input frame and obtain the global depth gradient accordingly. Thus it has a good adaptability to different image types.The algorithm detects the video shot and reuses the global depth gradient of frames within the same video shot to produce time-coherent depth maps, which reduces computational complexity and promotes the temporal smoothness of generated 3D video.The rest of this paper is organized as follows: In the 2D-to-3D system, the procedure of depth map generation is essential. This algorithm thus mainly devises the depth map generation method. As for the procedure of filtering and DIBR, we adopt general methods. An input 2D video stream consists of a number of video shots and each video shot includes a sequence of frames taken using a single camera. As the camera moves slightly within a video shot, the global depth gradient is changed slightly and it can be shared by frames in the same video shot to reduce the computational complexity and promote the temporal smoothness of the depth maps with little extra inaccuracy, which is proved by our experimental results in An input video stream is composed of a series of video shots. Video shot changes come in different types such as hard and gradual. A cut is a hard shot change which occurs in a single frame. Gradual type changes come in many forms including dissolve, wipe, fade in and fade out, and are processed not in a single frame but through several frames. The features of two frames spanning a cut have more differences while the adjacent frames of gradual type have fewer differences.There are many methods of detecting a new video shot frame based on computing frame differences, such as pixel differences, statistical differences, edge differences and so on . Color hAs is shown in Equation (2), the color histogram difference is calculated between the input frameThe frame of a hard shot can be easily distinguished by the color histogram difference because the change of color histogram between two adjacent frames spanning a cut is very obvious. The method of adaptive twin thresholds for video shot frame detection has already been proposed and proved effective ,8,9, so ot frame .We make use of a sliding window to determine the adaptive thresholds. The sliding window is from the previous video shot frame to the frame before the input frame, and the length of the sliding window is L. L is not a fixed value; it depends on the number of frames from the previous video shot frame and the number of the input frame. Average frame-to-frame color histogram differenceN is the first frame number of the sliding window, that is, N is the previous video shot frame number. M is the number of the frame before the input frame.resholds ,9.If an input frame belongs to a new video shot, the global depth gradient is computed through the frame and reused in other frames within the same video shot. Global depth gradient is computed according to the image type. Three categories of image types are defined in our algorithm: landscape type, linear perspective type and normal type. Landscape type refers to the images of outdoor scenery largely comprising land areas, water bodies and sky. Image of linear perspective type contain mainly vanishing lines which converge into a vanishing point. Other images belong to the normal type, such as indoor images, close-up images, personal images and so on.For a new shot frame, the algorithm first judges if it belongs to the landscape type. The landscape type is generally portrayed such that the upper part of the image is the sky and the lower part is the ground or water body such as a lake, river or sea. HSI color space was already transformed in the previous process of new shot frame detection and it is also used to detect the landscape type. A simple but effective judgement is adopted, as is shown in Equation (3). If the intensity value of a pixel is between 80 and 255 and its hue value is between 100 and 180, the pixel may belong to the sky or water body. If the saturation value is between 80 and 255 and its hue value is between 20 and 100, the pixel may belong to the ground [TLs. The threshold TLs is defined heuristically by experimental analysis as 0.5.As is shown in Equations (6) and (7), the proportion of the pixels belonging to the physical elements of the landscape in an image is computed and compared to the threshold If the frame does not belong to the landscape type, the algorithm then judges if the image falls into the linear perspective type by the following procedure: a Hough transform is used to detect straight lines and a threshold is set to obtain main lines from the straight lines. If there are main lines, the intersection points of every two lines are computed. The algorithm also checks if these intersection points are within a predefined range. If so, the input frame can be classified as linear perspective type. The intersection point nearest to the central point of these points can be regarded as the vanishing point and the main lines converging to the vanishing point are regarded as vanishing lines. If the main lines are not detected or the intersection points are decentralized, the frame is classified as normal type. After the image type of input frame is determined, global depth gradient is generated accordingly. For the landscape type, the upper part of the image is the sky and the lower part is the ground or water. Cumulative horizontal edge histogram  is used For the linear perspective type, the vanishing point is considered to be the farthest point in the image. The vanishing lines divide the image into horizontal planes and vertical planes. The depth gradients in different planes are assigned separately. In horizontal planes, the depth gradient value is constant along the rows. In vertical planes, the depth gradient is constant along the columns . Figure (1)Divide the image into N blocks:(2)A threshold(3)Make use of the main blocks individually, assign(4)Then fuse them together by the weight ofFor the normal type, numerous edges representing abundant details attract viewer’s attentions. Consequently, a closer depth is assigned to the regions containing more edges. The main steps are as follows:As is shown in Equations (9) and (10), the weights and the fused global depth gradient are calculated. After the global depth gradient of input frame is obtained, it is then refined by local depth information to generate a depth map. Warm/cool color theory suggests that the warm color gives viewer a nearer feeling while cold color is farther in visual perception  so the cglobal,D,Cr and Y components of the YCbCr-color space are normalized asThe procedure of filtering and DIBR are relatively fixed, so we adopt general methods to implement them. Depth map smoothing can reduce the number of holes generated during the virtual view synthesis in the DIBR procedure and help to improve the image quality of virtual views . GaussiaDepth-Image-Based-Rendering (DIBR) is then processed to generate stereoscopic video content. There are three steps of DIBR process: disparity computation, pixel-shifting and hole-filling . DispariPixel-shifting renders a virtual image by projecting the pixels of the original viewpoint to another viewpoint according to calculated disparity. Due to the disocclusions appear in another viewpoint, the hole-filling process is to fill in the newly exposed areas to form a complete image in the virtual viewpoint. After the two-view video content is produced through DIBR procedure, we can make use of 3D display technologies to enjoy 3D video. 3D display technologies include anaglyph 3D display, polarization 3D display and active-shutter 3D display.In this section, we first give some experimental results of different important parameters used in the proposed algorithm, then we designed different experiments to evaluate the proposed algorithm. To evaluate the adaptability of the proposed algorithm to different image types, various video sequences such as “Timescapes” and “Country Road” were tested as they contain abundant scene types. To evaluate the benefit of the reuse of the global depth gradient in the proposed algorithm, calculation instead of reuse of global depth gradient in each frame within the same video shot is also conducted in our experiment. By comparing them in terms of similarity and processing time, we can evaluate the reasonableness and necessity of the reuse of the global depth gradient. To evaluate the advantages of the proposed algorithm, three algorithms were adopted as reference. Average processing time and subjective testing outcome are compared between them.TLs for the image type of landscape, we tested 120 pictures from the Imagenet database. Sixty pictures belong to landscape type and sixty pictures do not belong to landscape type. Precision rate, recall rate and F score are often used to evaluate the effectiveness of method for classification [TLs, the F score can reach the highest value among these values. Consequently, we choose 0.5 as the value of threshold TLs.To determine the threshold fication . Table 1For the normal type, the image is firstly divided into N blocks. The value of 4 × 4 is adopted as the parameter N in our experiment. From the comparision we can find that when N is adopted as 4 × 4, the effect of global depth gradient and final depth map is as good as N equal to 5 × 5 and the effects are both better than the N equal to 3 × 3. However, when N is adopted as 4 × 4, there are less branching global depth gradients and the computational complexity is less than N equal to 5 × 5. Consequently, the parameter N is set to 4 × 4 in the proposed algorithm.For the fusion of global depth gradient and local depth information, we should determine the values ofWe can find that whenThe reuse of global depth gradient is another innovation point in the proposed algorithm. As the camera moves slightly within a video shot, the image type of these frames within a video shot does not change and the global depth gradient is changed only slightly during the generation process. As a result, there is no need to calculate the global depth gradient in every frame. Reuse of the global depth gradient within the same video shot brings the benefits of saving time and promoting temporal smoothness with little added inaccuracy. In the experiment, we calculated global depth gradient for every frame in a video shot and then compared them with the reused global depth gradient calculated in the first frame of this video shot, as is shown in As the range of value for depth map is from 0 to 255, a tiny change in value of a pixel such as 10 or 15 in a depth map can be acceptable. Although we cannot distinguish the difference with our eyes in the above figure, we computed the similarity between the calculated and reused global depth gradient of the frames within a video shot. The similarity value between two gray images is a percentage which divides the number of pixels whose value changes are under a tolerant value by the number of total pixels in an image. We set the tolerant value change as 10 and 15 respectively.From To make a comparison of processing time, we processed every frame by the procedure of global depth gradient calculation, local depth refinement, filtering and DIBR without the reuse of the global depth gradient. Average processing time of above procedure is listed as procedure 1 in From To evaluate the proposed method, we also compare the proposed algorithm with other algorithms. Four video sequences, “Air”, “Arctic”, “Fashion” and “Cod” from , are tesSubjective assessment was performed as well. A slightly modified version of single-stimulus presentation method in ITU-R BT.500-11  was used2D-to-3D video conversion method can make use of 2D video data based on ordinary image sensors to produce 3D video data, which means it can be adopted in a 3D image sensor, which is composed of a general 2D image sensor and the 2D-to-3D chip. This paper presented a novel algorithm for 2D-to-3D video conversion which can be used in the 2D-to-3D chip in the future. The proposed algorithm produces time-coherent depth maps by detecting new video shot frames, generating global depth gradients and supplementing with local depth information. The innovation of generating global depth gradients for different image types can produce good adaptability to different scenes and produce better stereoscopic effects for the generated 3D video. The reuse of global depth gradient can reduce the overall processing time in the 2D-to-3D system. This innovation can also improve the temporal smoothness of generated 3D video, which reduces eye fatigue for viewers and leads to a comfortable visual experience.


Supplemental Digital Content is available in the text Although adequate bowel preparation is a prerequisite for colonoscopy, preparation among inpatients is often suboptimal. This study aimed to evaluate the impact of ward nurse education on the quality of bowel preparation of inpatients.A prospective, double-blinded, non-randomized, controlled study was performed. Expert endoscopists provided enhanced education to nurses who belonged to an “educated ward” followed by training that was repeated every week for 1 month. The primary outcome was the quality of the bowel preparation, which was based on the Ottawa Bowel Preparation Scale (OBPS). Patient compliance and their subjective feelings and the factors affecting inadequate bowel preparation were also analyzed.P < 0.001). The rate of poor preparation (OBPS ≥ 6) in the educated ward was significantly lower than that in the control ward . Compliance with preparation and diet instructions in the educated ward was superior to that in the control ward (P<0.001). Control patients were more likely to be anxious before colonoscopy (P < 0.001), whereas patients in the educated ward showed higher level of satisfaction (P = 0.001) and better sleep quality (P < 0.001). A lack of ward nurse education , constipation , and insufficient water ingestion  were independently associated with inadequate bowel preparation among inpatients.One hundred three inpatients in the educated ward and 102 patients in the control ward were enrolled. Baseline data were comparable between the 2 wards. The mean values of the total OBPS scores were 4.42 ± 2.23 and 6.15 ± 2.38 in the educated and control wards, respectively (Ward nurse education effectively improved the quality of bowel preparation, and relevant colonoscopic outcomes among inpatients. Additional efforts are needed to control constipation and to encourage additional water ingestion in inpatients for better bowel preparation. The quality of bowel preparation among inpatients is poorer than that among outpatients.4 Hence, several studies have suggested educational tools to enhance a patient's comprehension and compliance for better bowel preparation quality.7 However, most studies in the area of education for bowel preparation have focused on outpatients and not on inpatients.During bowel preparation, patients are required to cooperate actively with respect to the prescribed purgative and diet instructions. Many patients, however, often misunderstand these complicated requirements, and as a result, it is a great challenge for them to complete their bowel preparation successfully.9 Educated nurses reported the resolution of their “uncertainty and lack of confidence” after the education was provided, which allowed them to provide effective care and appropriate information to their patients.9The additional education for nurses has been attempted in diverse hospital settings to provide optimal care to inpatients, and most of these efforts resulted in improved clinical outcomes.Therefore, we aimed to investigate the effect of nurse education on the quality of bowel preparation for inpatient colonoscopy. We also evaluated colonoscopy outcomes as well as the compliance and subjective feelings of the patients.www.ClinicalTrials.gov registry (NCT01911026).This study was a prospective, double-blinded, nonrandomized controlled trial conducted at a tertiary hospital in South Korea. The participants were assigned to the educated ward or to the control ward. The study protocol was approved by the institutional review board of our institution. Written informed consent was obtained from all participants. This study was published in the Between July 2013 and January 2014, patients aged 19 to 80 years who were admitted to 2 gastroenterology wards of the hospital and who were scheduled for a nonurgent colonoscopy were recruited. Patients were excluded for the following reasons: known hypersensitivity to polyethylene glycol (PEG); severe congestive heart failure (New York Heart Association [NYHA] grade III or grade IV); severe renal insufficiency (creatinine clearance <30 mL/minutes); hemodynamic instability; suspected intestinal obstruction or perforation; compromised swallowing reflex or altered mental status; and, among women, pregnancy or lactation. Patients undergoing an unscheduled colonoscopy or who declined to participate were also excluded.After they agreed to participate, the patients were consecutively admitted to one of the wards as rooms became available. Any systematic allocations by the investigator were not allowed during the assignments of the wards. Patients in the educated ward received explanations of the steps required for bowel preparation from intensively educated nurses, whereas patients in the control ward received the standard explanations from nurses who had received no enhanced education.http://links.lww.com/MD/A389).At the beginning of this study, we performed a preliminary test with pilot study samples (each group consisted of 30 patients) to clarify any differences between the patients in the 2 wards. As a result, no significant differences were observed in terms of the patient demographics, the quality of bowel preparation, colonoscopy outcomes, subjective feelings, or compliance with the instructions  , which contained 100.0 g PEG, 7.5 g sodium sulfate, 2.7 g sodium chloride, 1.0 g potassium chloride, 4.7 g Asc, and 5.9 g sodium ascorbate per l, was ingested at the rate of 250 mL every 10 minutes. For colonoscopies performed in the morning, a split-dose bowel preparation regimen was followed: ingestion of a half-dose of purgative at 8:00 pm on the day before the procedure and the remaining 1 l on the morning of the procedure. For colonoscopies performed in the afternoon, patients were asked to consume a full dose (2 l) of PEG + Asc between 6:00 and 8:00 am on the day of procedure. Additionally, patients were instructed to drink clear water until their stools did not show the presence of any brown effluent. All colonoscopies were performed between 2 and 8 hours after the purgative intake was complete.The methods of bowel preparation and diet restrictions were equally applied to all patients. The patients were prescribed low-residue diets at least 2 days before the scheduled colonoscopy; they were also advised not to ingest high-fiber foods. On the day before the colonoscopy, the patients were provided a soft diet for dinner before 6 Two expert colonoscopists (ESK and YJL) provided enhanced education, which consisted of a leaflet and a lecture, to nurses who belonged to the educated ward. The enhanced education explained the importance of bowel preparation and the possible adverse effects during bowel preparation  for the purpose of reducing a patient's anxiety. This training also explained the precolonoscopy diet and the rationale for this diet, the instructions for completion of the purgative, and the importance of drinking additional water as needed. During the lecture, nurses were allowed to pose any questions. The leaflet was placed on the wall of the educated ward, and brief review training sessions for nurses were repeated every week for 1 month. No additional education was provided to nurses who were assigned to the control ward.The primary outcome was the quality of bowel preparation as measured by 5 expert colonoscopists  who each had experience with over 2000 colonoscopies. Factors affecting inadequate bowel preparation, as assessed by the proportions of inadequate bowel preparation were also identified. The secondary outcomes were the subjective feelings of the patients during the preparation, their compliance with the instructions and colonoscopic outcomes such as the adenoma detection rate (ADR) and the rate of incomplete colonoscopy.10 During the study period, the OBPS usage manual, which contains representative colonoscopic images of each score, was posted to the wall of the endoscopic procedure room. Prior to patient enrollment, the participating colonoscopists received standard instructions on how to use the bowel preparation scale to reduce possible interobserver variation. Then, a pilot study was performed to ensure interobserver agreement for the rating of the preparation quality using 20 colonoscopies. As a result, a high level of interobserver agreement was achieved (k = 0.87).The Ottawa Bowel Preparation Scale (OBPS) was used to evaluate the quality of bowel preparation. An assessment was performed on the overall fluid volume  of the entire colon as well as its cleanliness, which was rated from 0 to 4 , for the right colon, mid-colon, and rectosigmoid colon. The total OBPS score was calculated as the sum of the overall fluid volume and each of the segmental scores and ranged from 0 to 14; a higher score indicates poorer preparation.am and 4:00 pm. To ensure that the colonoscopists were blinded, information regarding the patient's ward was not revealed to the colonoscopists; to this end, we removed the room number and the ward of the patient from the colonoscopy report form and from the patient's personal items. Colonoscopists were instructed not to ask the patients about the wards to which they were admitted. Only 1 endoscopy nurse who was not involved in the study identified a patient's ward information. Patients had the choice of conscious sedation or not during the procedure. However, the decision was ultimately determined by the individual colonoscopist after consideration of the patient's clinical status. Immediately after the colonoscopy, the colonoscopists recorded the OBPS score which was applied when scope withdrawal and the detailed outcomes such as cecal intubation time, withdrawal time, and colonoscopic findings. ADR was defined as the proportion of colonoscopies with at least 1 adenoma was detected.11All colonoscopies were performed with conventional video endoscopes between 10:00 On the day of the colonoscopy, 1 trained nurse who was unaware of the allocated groups of the patients interviewed all patients before their procedure. Then, the collected data were immediately entered into a prepared form in a database. The information obtained through interview was as follows: patient's characteristics, the amount of remaining purgative, how closely the patient followed the dietary restrictions, how strictly the patient followed the instructions for the purgative, whether the patient ingested additional water if needed, the degree of sleep disturbance, patient's anxiety and satisfaction with preparation, adverse events during bowel preparation, willingness to repeat the same preparation, and completion time of purgative ingestion.12 Compliance with the dietary and preparation instructions was classified as high (over 50%) or low (below 50%). The question regarding “additional water ingestion if needed” was assessed with “yes” or “no” answer. Similarly, the presence of sleep disturbance and willingness to repeat the same preparation were also indicated with a “yes” or “no” response.Constipation was defined as having at least 2 of 6 specific bowel symptoms including straining, lumpy or hard stools, incomplete evacuation, sensation of anorectal obstruction, manual maneuvers for defecation, and ≦3 defecations/week.7 The preparation-to-colonoscopy (PC) interval, which was defined as the time from the completion of purgative intake to the start of the procedure, was measured in all patients.13According to previous reports, patient's anxiety and satisfaction were rated on a 5-point scale .3 To obtain a 20% improvement (from 50% to 70%) in the occurrence of adequate bowel preparation in the nurse educated ward, a sufficient sample size per group was found to be 90 at a 2-tailed 5% significance level with a power of 80%. Considering a 10% dropout rate, we estimated that a minimum of 100 patients per group were needed.Calculation of the sample size was based on the result of an earlier study that determined an adequate bowel preparation of inpatients as 50%.t-tests were used for continuous variables. A logistic regression analysis was performed to assess the factors associated with inadequate bowel preparation (OBPS ≥ 6). Variables that reached a P value of <0.05 by univariate analysis were analyzed in a multiple logistic regression model. A P value of <0.05 was considered statistically significant. Statistical analysis was performed using SPSS software .The categorical variables were analyzed by Chi-square tests or Fisher exact tests. Student's A total of 255 patients who were scheduled for a colonoscopy in 2 gastroenterology departments during the study period were screened. Of the 129 who were admitted to the educated ward and of the remaining 126 who were admitted to the control ward, 45 who met the exclusion criteria were excluded. Five patients canceled their colonoscopy appointment. Finally, 103 inpatients in the educated ward and 102 patients in the control ward underwent colonoscopy. Figure P = 0.016), whereas the withdrawal times were not different between the 2 groups (P = 0.610). The mean PC interval was also shorter in the educated ward than in the control . Notably, the ADR was significantly higher in the educated ward compared with the control  although it lost its significance after eliminating patients who were referred to the hospital for the treatment of recently diagnosed colonic neoplasms. No differences were observed between the 2 groups in terms of the cecal intubation rates, causes of incomplete colonoscopy or average doses of sedative agents. None of the patients reported severe adverse events.The colonoscopy outcomes of each group are presented in Table P < 0.001). The proportion of patients with inadequate bowel preparation (OBPS ≥ 6) was significantly lower in the educated ward compared with the control .Table P < 0.001). The reported anxiety was lower in patients in the educated ward than in control (P < 0.001). Patients in the educated ward also reported better satisfaction than patients in control (P = 0.001). However, no differences were observed between the 2 groups in the reported preparation-related adverse symptoms and in the proportion of patients who were willing to undergo the same preparation again . Preparation instructions were also more closely followed in the educated ward than in control . Similarly, the proportion of patients who complied with the dietary instructions was higher in the educated ward than in control . With regard to the recommendations of additional water intake as needed, more patients in the educated ward followed this recommendation than did patients in control .Table P < 0.001), a lack of ward nurse education (P < 0.001), low compliance with preparation instructions (P = 0.002) and dietary instructions (P = 0.001), and no additional water ingestion (P < 0.001) were revealed as factors related to inadequate bowel preparation (Table P < 0.001), a lack of ward nurse education , and no additional water ingestion   showed inadequate bowel preparation OBPS ≥ 6). In univariate analysis, the presence of constipation . The Aronchick scale is the first validated scale to make global assessment of the entire colon, without provision for assessing individual segments.Our study has certain strengths. First, not only were various clinical factors that may negatively impact the quality of bowel preparation studied, but other important aspects, including a patient's subjective feelings and compliance during the preparation, were also assessed in this study. Second, we used the OBPS, which is a validated and widely adapted scale for evaluating the quality of bowel preparation. Moreover, we tried to reduce the interobserver variability based on a pilot test comparing OBPS ratings among the colonoscopists. Third, to avoid the possibility of selection bias, we unified the preparation regimen including the prescribed purgative agent, the timing, dose, and method for purgative ingestion, and we controlled the PC time within the range of 2 to 8 hours. Lastly, we identified factors that are related to inadequate bowel preparation in inpatients. These factors may be helpful in determining inpatients who might be at greater risk for inadequate bowel preparation.The current study also has several limitations. First, this was not a randomized study. The allocation of patients to each ward could not be randomly controlled due to administrative constraint at the hospital. Therefore, some unexpected confounding factors resulting from selection bias may affect the process and results of this study. However, to overcome the shortcomings associated with nonrandomization, we strictly controlled the blinding of the patients and investigators during the prospectively designed study periods. Through a pilot study, we also verified that the prestudy patient characteristics and study outcomes were well balanced between both groups. Second, this study was conducted in a single institution, and we only included patients who were hospitalized in the gastroenterology department. Therefore, care should be taken in the generalization of these findings. Third, we did not evaluate the duration of the effect of education.Our findings suggest the importance of enhanced education for frontline nurses that can be easily applied in a real clinical practice with lower demand on resources. Thus, clinicians should consider the application of ward nurse education in each healthcare facility for achieving better bowel preparation in inpatient's colonoscopy.In conclusion, enhanced education of ward nurses is effective because it leads to a better quality of bowel preparation and improves the patients’ subjective feelings and compliance in inpatient colonoscopy. Additional efforts to control constipation and to encourage additional water ingestion are needed to improve quality of bowel preparation among inpatients.


Accurate measures of alcohol consumption are critical in assessing health harms caused by alcohol. In many countries, there are large discrepancies between survey-based measures of consumption and those based on alcohol sales. In England, surveys measuring typical alcohol consumption account for only around 60% of alcohol sold. Here, using a national survey, we measure both typical drinking and atypical/special occasion drinking  in order to develop more complete measures of alcohol consumption.A national random probability telephone survey was implemented (May 2013 to April 2014). Inclusion criteria were resident in England and aged 16 years or over. Respondents  provided information on typical drinking  and changes in consumption associated with routine atypical days  and special dinking periods  and events . Generalized linear modelling was used to identify additional alcohol consumption associated with atypical/special occasion drinking by age, sex, and typical drinking level.Accounting for atypical/special occasion drinking added more than 120 million UK units of alcohol/week (~12 million bottles of wine) to population alcohol consumption in England. The greatest impact was seen among 25- to 34-year-olds with the highest typical consumption, where atypical/special occasions added approximately 18 units/week (144 g) for both sexes. Those reporting the lowest typical consumption (≤1 unit/week) showed large relative increases in consumption (209.3%) with most drinking associated with special occasions. In some demographics, adjusting for special occasions resulted in overall reductions in annual consumption .Typical drinking alone can be a poor proxy for actual alcohol consumption. Accounting for atypical/special occasion drinking fills 41.6% of the gap between surveyed consumption and national sales in England. These additional units are inevitably linked to increases in lifetime risk of alcohol-related disease and injury, particularly as special occasions often constitute heavy drinking episodes. Better population measures of celebratory, festival, and holiday drinking are required in national surveys in order to adequately measure both alcohol consumption and the health harms associated with special occasion drinking.The online version of this article (doi:10.1186/s12916-015-0337-0) contains supplementary material, which is available to authorized users. Alcohol is related to over 200 different health conditions with recent estimates suggesting it was responsible for 5.1% of the global burden of disease and injury (disability adjusted life years) and 3.3 million deaths in 2012 . HoweverTypically, data on trends and demographic variation in alcohol consumption are provided by large-scale surveys and records of amounts of alcohol products sold for consumption . Thus, iA number of hypotheses have been suggested to explain such differences. These include underestimation of the size of generic drinks reported in surveys, poor recollection, and other reporting biases of consumption by survey participants, and an inability to capture some heavier drinkers in the survey samples -16. To aDrinking patterns are rarely regular or unchanging, rather, they are characterised by peaks and troughs in consumption depending on weekday, season, and special occasions. Survey methods that attempt to directly measure temporal and contextual changes in individuals’ alcohol consumption provide better measures of alcohol consumption which are more consistent with levels of alcohol sales. Thus, the Graduated-Frequency methodology ,22 asks Herein, we describe a new method to measure both typical alcohol consumption and changes in levels of consumption associated with holidays, festivals, sports events, weddings, bereavements, and other special events over a 12-month period (Box 1). We utilise this methodology to undertake a large national survey in a country (England) with a drinking culture historically characterised by low levels of routine drinking interspersed with periods of heavier, social consumption -26. We uRespondents were asked if they had ever consumed alcohol and if they had drank in the last 12 months. For those responding yes to both questions (classed as current drinkers), detailed information about alcohol consumption was collected in three domains: typical drinking, routine atypical drinking, and special occasion drinking.On average, how often have you drank alcohol in the last 12 months”. Responses were recorded as number of days per week or, for those drinking less than weekly, categories of 2 to 3 days per month, 1 day per month, or less often . Participants were then asked a series of questions to describe how much they would normally drink on a typical day when drinking, with the number of drink types and sizes recorded. Consumption was recorded separately for settings inside (private space) and outside (public space) of the home. Mean quantity of alcohol consumed per week  was calculated using the conversion criteria outlined in Box 2. Individuals were classified by sex to categories of typically weekly consumption based on those used by national statistics .Individuals were first asked if there were days in the last 12 months when they drank a bit more, a lot more, or less than usual. Respondents who acknowledged having such days were asked to estimate how much they drank on these days .To capture routine atypical days  the frequency of such days was reported . In each scenario, individuals also identified if the drinking days were in addition to, or instead of, typical drinking days. Combined with typical drinking days these measures provided a total number of drinking days in a year across the four possible consumption levels  for each respondent . The saPhone numbers were called a maximum of seven times . Calls resulting in contacts with fax machines, business addresses, and dead lines were removed. No answers, call back requests, and answer machines were called until a respondent provided either a yes  or no , or the study end date was reached. Of the 6,092 completing the survey, 6,085 individuals provided all data items required. Consequently, the response rate was calculated as 23.3% .2 and ANOVA were used to examine differences in abstinence and consumption between demographic categories. Generalized Linear Modelling (GLM) was used to measure independent relationships between demographics and changes in consumption identified through enhanced survey measures , and the best fit model used to generate correction factors from reported typical to adjusted consumption by age, sex, and typical weekly drinking category. Finally, modelled corrections were applied to the England population using age, sex, and nationally reported consumption categories . EthicaDemographics and alcohol drinking behaviours are shown in Table Amongst drinkers, neither ethnicity nor deprivation were significantly associated with typical weekly consumption, adjusted consumption, or adjustment size Table . TypicalTo account for confounding between demographics, GLM was employed to model independent levels of adjustment associated with each independent variable. Dependent variables were limited to those showing a significant association with levels of adjustment Table  and all HSE provides national estimates of non-drinkers and proportions in each typical consumption category by sex and the same age categories used here . These wThe total units of alcohol cleared for sale in England  are equFestive drinking, often as a counterpoint to the norms of daily sobriety, has a long history in many societies . Recent The additional units associated with atypical and special occasion drinking can be disproportionately damaging to health. Thus, atypical and special occasion drinking is often associated with bingeing and, therefore, with increased risks of unintentional injury and violence as well as overdose and alcohol poisoning . FurtherEven with special occasion drinking taken into account, 4.6 units/drinker/week  remain unaccounted for in sales data. Other hypotheses may account for this inconsistency , such asAlthough randomised, the survey did not attempt to generate a representative sample of alcohol consumers and abstainers on a national basis, but instead used national population estimates and stratified drinking survey data to weight responses to the English population. With this survey acting as a proof of concept, a larger nationally representative survey is now required to test the independent utility of this methodology as a national monitoring tool. For special drinking events Box 1) we were also unable to distinguish if they were instead of or as well as other drinking days. Here, we opted for a conservative measure by removing an average drinking day’s consumption for each special event day reported. How often such occasions should be considered additional consumption requires further study. Participation rates were 23.3% of those contacted and informed about the study and our sample over-represented females, older individuals, and those of white ethnicity  have been typified by lower levels of routine alcohol consumption interspersed with heavier social consumption ,33. ThisDisproportionate underestimation of alcohol consumption by infrequent drinkers has been identified elsewhere . ConsistParticipants were asked if their frequency of alcohol consumption or amount consumed when drinking changed from their reported typical on any of the occasions and events listed below. For special periods, those indicating changes in consumption level and/or frequency were asked how often they drank , how much they drank , and for how long each occasion lasted . For events, changes in level of consumption associated with the event type were recorded  and then for each event the number of times (days) on which they had occurred in the last 12 months recorded.Period around Christmas and New YearIn the summerWhen on holiday at homeWhen on holiday away from homeBank holiday weekendsWorking away from homeIn January (after New Year)During other religious periods, e.g., Lent, RamadanAfter a bereavement or funeralDuring periods of unemployment or other change in work patternsSpecial periodsWhen celebrating own, a friend’s, or a close relative’s birthdayAt a weddingAt an engagement, hen, or stag partyWatching an important sporting event on TV or liveWhen friends came to stay or you stayed with friendsAt a festival, rock or pop concert, or other showSpecial eventsaLow strength, 2.8% ABV, e.g., Regular bottle, 330 mL, 0.9 UK units, 7.4 gMedium strength, 4.5% ABV, e.g., Regular can, 440 mL, 2.0 UK units, 15.8 gHigh strength, 6.5% ABV, e.g., Pint, 568.3 mL, 3.7 UK units, 29.6 gBeer and Cider b12.5% ABV, e.g., Medium glass, 175 mL, 2.2 UK units, 17.5 gWine c17.0% ABV, e.g., Double, 50 mL, 0.9 UK units, 6.8 gFortified Wine/Liqueur c40.0% ABV, e.g., Single, 25 mL, 1.0 UK units, 8.0 gSpirits d4.0% ABV, e.g., Small bottle, 275 mL, 1.1 UK units, 8.8 gAlcopops 40.0%, One size, 50 mL, 2.0 UK units, 16.0 gCocktailsa For beer and cider, small and regular bottle and can size were recorded as well as litre and half litre options. b As well as three glass sizes , home drinking respondents were asked how many glasses they normally get from a standard bottle (750 mL) in order to calibrate their home poured glass size. Respondents could also report consumption of wine in fractions of a bottle . c For spirits, liqueurs, and fortified wines, individuals identifying drink sizes above doubles were set as triples. Individuals could also report consumption as a fraction of a bottle size. d For alcopops, both small (275 mL) and large (700 mL) bottles were recorded. ABV, Alcohol by volume; g, grams of pure alcohol.Males, ≤1 UK unit/week, ≤8 g/weekFemales, ≤1 UK unit/week, ≤8 g/week(Lower Risk)Males, >1–10 UK units/week, >8–80 g/weekFemales, >1–7 UK units/week, >8–56 g/week(Lower Risk)Males, >10–21 UK units/week, >80–168 g/weekFemales, >7–14 UK units/week, >56–112 g/week(Lower Risk)Males, >21–35 UK units/week, >168–280 g/weekFemales, >14–21 UK units/week, >112–168 g/week(Increasing Risk)Males, >35–50 UK units/week, >280–400 g/weekFemales, >21–35 UK units/week, >168–280 g/week(Increasing Risk)Males, >50 UK units/week, >400 g/weekFemales, >35 UK units/week, >280 g/week(Higher Risk)Typical weekly drinking categories based on Health Survey for England .


Melanopsin containing intrinsically photosensitive Retinal Ganglion cells (ipRGCs) mediate the pupil light reflex (PLR) during light onset and at light offset . Recent evidence shows that the PLR and PIPR can provide non-invasive, objective markers of age-related retinal and optic nerve disease; however there is no consensus on the effects of healthy ageing or refractive error on the ipRGC mediated pupil function. Here we isolated melanopsin contributions to the pupil control pathway in 59 human participants with no ocular pathology across a range of ages and refractive errors. We show that there is no effect of age or refractive error on ipRGC inputs to the human pupil control pathway. The stability of the ipRGC mediated pupil response across the human lifespan provides a functional correlate of their robustness observed during ageing in rodent models. Thus, the data from 59 participants were analysed. None of the participants were taking any prescription medication known to affect the pupil light response. All 59 participants had a visual acuity of 6/9.5 or better (Bailey-Lovie Log MAR Chart), normal contrast sensitivity (Pelli-Robson Chart), normal color vision (Lanthony Desaturated D-15 Test), an intraocular pressure of <21 mmHg , and normal central retinal thickness . Anterior and posterior eye examination using slit lamp biomicroscopy and funduscopy revealed no pathology. Lens grading was conducted according to the Lens Opacities Classification System III (LOCS III) guidelinemax = 448 nm, corneal irradiance: 14.5 log quanta.cm−2.s−1, luminance: 1.3 log cd.m−2) with high melanopsin excitation (609.8 α-opic lux) and red light  with low melanopsin excitation (9.7 α-opic lux). Blue light measures the intrinsic melanopsin response and red light measures the outer retina response and serves as a control (see Quantification of the PLR and PIPR section for details). During pupil recording, the participants fixated on a green cross in the center of the field at infinity through a pair of 50 mm objective lenses . The test stimulus was presented in Newtonian view to one eye and the PLR of both eyes was recorded under infrared illumination.The pupil light reflex was measured using the RAPDx pupillographer . This instrument is designed to measure the relative afferent pupil defect (RAPD) and new customised paradigms with high irradiance stimuli were developed for measuring the PIPR. The RAPDx presents light stimuli with a 25° field of view using a liquid crystal display (LCD) with a 40 Hz frame rate. The spectral, radiometric, and photometric outputs of the stimuli were measured with a Spectroradiometer  and an ILT1700 Research Radiometer . The monochromatic stimuli included 1 s and 10 s pulses of blue light . Testing with 1 s light pulses always preceded the 10 s pulses . Red and32et al.et al.68111735The PLR during light stimulation was quantified using the transient PLR and peak pupil constriction metrics described in F-test . Paired t-test was used to calculate the difference in the PLR and PIPR amplitudes between outcome variables  and the difference in the 6 s PIPR amplitude between blue and red stimuli (P < 0.05). To quantify the variability of the PIPR metrics, the intra- and inter-individual Coefficient of Variation (CV) was calculated as Standard Deviation (SD) divided by the Mean. Intra-individual CV was based on the difference between the repeats for the same participant and inter-individual CV was based on the difference among all participants. The difference in intra-individual CV among the PIPR metrics was tested with one-way ANOVA . To determine the effect of refractive status on the PLR and PIPR amplitudes, the difference in the PLR and PIPR amplitudes among participant sub-groups classified according to refractive status was tested with Kruskal-Wallis test (Geisser-Greenhouse correction) because the refractive error data distribution was non-normal. Due to low sample number with myopia (n = 13) and hyperopia (n = 3), the refractive error and pupil data were bootstrapped using Microsoft Excel 2010 Statistical data analysis was conducted using GraphPad Prism . The effect of age on the PLR and PIPR metrics was the primary outcome and the effect of refractive error on the metrics was the secondary outcome. Age and refractive error were independent (predictor) variables and the PLR and PIPR metrics given in A total of 59 participants  were included in this study with an age range between 21 to 70 years (mean age ±SD: 43.7 ± 14.4 years) and there was equal distribution of participants in each age decade. The mean ± SD central retinal thickness was 272.72 ± 24.02 μm and the slope of the regression line  was not 39t-test: t(57) = 20.07, P < 0.001) due to the higher melanopsin excitation with the short wavelength (blue) light. The slopes of the regression lines were not significantly different from zero for any PIPR metric indicating the PIPR amplitude is independent of age.During light stimulation, the slopes of the regression lines describing the transient PLR and peak pupil constriction data were not significantly different from zero for red and blue lights indicating that these metrics are independent of age . We dete2 = 0.130, P = 0.01), validating the use of percentage (%) BPD to describe the PLR and PIPR metrics (The baseline pupil diameter (BPD) measured in the dark decreases significantly with age in agreement with previous studies 173536. T1735 metrics .P = 0.68; red light: H = 0.35, P = 0.84) or the 6 s PIPR amplitude . The transient PLR (data not shown) was also unaffected by refractive status.The refractive status of 39 participants was known and the refractive error ranged from +3.00 D to −9.25 D . Due to a small sample of refractive errors, we bootstrapped the data to obtain an estimate of the sampling distribution for regression analysis . The slopes of the best-fitting linear regression lines to the bootstrapped data  were notF3,196 = 41.45, P < 0.001). Post-hoc analysis indicated that the intra-individual CV for the 6 s and plateau metrics was significantly different to the AUC metrics, with a lower variation for the 6 s and plateau metrics compared to the AUC metrics  was calculated . The int metrics . SimilarThe primary outcome of this study shows that ageing has no effect on the Post-Illumination Pupil Response (PIPR) indicating that the intrinsically photosensitive Retinal Ganglion Cell (ipRGC) inputs to the pupil control pathway show no change with age. The 6 s and plateau PIPR metrics demonstrated the lowest intra- and inter-individual coefficient of variation. The secondary outcome indicates that the PIPR is independent of refractive status.et al.et al.This is the initial study showing the PIPR amplitude , which is entirely driven by the intrinsic response of melanopsin expressing ipRGCs, is independent of age . Kankipaet al.In accordance with Kankipati It has been suggested that reduction in light stimulated pupil size (in mm) with age is related to decrease in BPD due to iris atrophy and impaired sympathetic nerve supply to iris with age36Earlier studies investigating the relationship of refractive error and the light-adapted pupil size demonstrate either a weak negative correlation 25271920−2.s−1) and shorter dominant wavelength (448 nm) than melanopsin peak sensitivity in the commercial pupillometer compared to our recent studyWe found no significant difference between direct and consensual PLR and PIPR amplitudes using monochromatic 1 s and 10 s blue and red light pulses in the central 25° , althougin vivo models. We further present the initial and novel findings suggesting that the ipRGC controlled PIPR is also independent of refractive error.In conclusion, this is the first study showing that ipRGC function measured with all current PIPR metrics is unaffected by ageing thus providing a functional correlate of their robustness throughout lifespan as observed in rodent How to cite this article: Adhikari, P. et al. Effect of Age and Refractive Error on the Melanopsin Mediated Post-Illumination Pupil Response (PIPR). Sci. Rep.5, 17610; doi: 10.1038/srep17610 (2015).


Musculoskeletal and limb defects (MLDs) are the major categories in hereditary anomalies and are a significant source of the disabilities. This study aimed at elucidating the nature and pattern of MLDs prevalent in Chitral district, which is an isolated population in the North-West of Pakistan.A cross-sectional epidemiological study was conducted in Chitral and subjects/families with MLDs were ascertained from public places, hospitals and door-to-door visits. The phenotypic manifestations, expressivity, sporadic/familial presentations, isolated/syndromic nature, inheritance pattern, and socio-demographic attributes, of MLDs were observed.A total of 153 independent subjects/families with certain types of MLDs were recruited. The MLDs were classified into 9 major and 22 minor entities. In this cohort, polydactyly was observed to be overwhelmingly common (71%), followed by syndactyly and absence limb deformities. The majority of the cases (78%) had sporadic nature, 93% anomalies had isolated presentations; upper limbs were more commonly affected than the lower limbs; and unilateral cases were twice in ratio than bilateral. The majority of the malformations had milder phenotypes, however, 17% of the MLDs were severe in nature and resulted in certain types of disability, compromising the normal life of the subject.This research witnesses a distinctive pattern of MLDs in Chitral, which has not been reported for any other population of Pakistan so far. Further studies are required to observe the molecular etiologies of these malformations and to offer rapid diagnosis and genetic counseling. The majority of the Mendelian or monogenic diseases are relatively rare individually, but collectively they become quite common. With the advent of better surveillance and stringent interventions infectious/communicable diseases are declining globally, however, hereditary and genetic disorders emerge as a major burden on the healthcare-systems.2MLDs may have mild to severe nature. The anomalies which are restricted to one organ-system and do not seriously affect the quality of life may be considered as milder types. These include for instance, digit defects like polydactyly, syndactyly, brachydactyly, etc. Severe anomalies like dwarfisms render long-term disabilities and are source of mortality in many instances.In Pakistan, high prevalence of genetic disorders has been reported. High rate of consanguinity, overlapping generations and stable communities have led to multigenerational pedigrees with several individuals exhibiting rare genetic disorders.This cross-sectional epidemiological study on MLDs was conducted during 2012-2013 in Chitral district of Khyber Pakhtunkhwa province. Subjects/families with certain types of MLDs were ascertained by visiting public places like educational institutes and community centers and through door-to-door surveys.An informed consent was obtained, either from the individuals or their parents. For each individual, detailed data were obtained on demographic variables. Each subject underwent a clinical and physical examination with the help of a local medical practitioner. Detailed pedigrees were drawn from the familial cases. However, only the index subject in each family was included in the analyses. The study was approved by the Ethical Review Committee of the Quaid-I-Azam University, Islamabad.2 and Fisher’s exact test statistics.MLDs were characterized with the help of a resident medical officer and by employing the standard medical databases.There were 153 independent subjects/families ascertained with MLDs. These malformations were classified into nine broad categories, and among those polydactyly had the highest representation , followed by syndactyly , absence deformities (n=9), musculoskeletal defects (n=6), talipes (n=5), contracture anomalies (n=4), brachydactyly (n=2), leg defects , and overriding toe (n=2) ; Fig.1. Male subjects were found to be commonly affected than the females in most of the ascertainment categories. For instance, in the total index cases the frequency of affected males was twice than that of females (M:F= 2.1:1). Among the sporadic cases (n=120), 84 males and 36 females were observed (2.3:1). In the familial index cases (n=33), there were 19 males and 14 females.The 153 index subjects had a total of 222 affected limbs . The uppIn 33 familial cases, the malformation was witnessed to segregate in one (n=14) or two generations (n=15). Across all pedigrees, the malformations were segregating 1.70±0.68 generations on average. Furthermore, the mean affected sibship per pedigree was calculated to be 1.70±0.68, while affected subjects per family averaged 3.06±1.77 (data not shown).nd , and 3rd gravida . The parity in all sporadic cases averaged 1.91±1.05.The 120 sporadic cases were analyzed with respect to the parity/gravida of the index subject and the size of his/her normal sibship. The majority of index subjects belonged to first parity , followed by 2MLDs had essentially isolated presentations in 93% (n=142) cases. Eleven index subjects were observed to have 16 associated malformations, the most common of which were syndactyly (n=5) and camptodactyly (n=3). There were 13 occasions in which certain other malformation was witnessed in the family members of the index subject.Distribution of subjects/families was established along the socio-demographic variables of the Chitrali population . In the In the present cohort, majority of the MLDs had rather milder nature. However, 17% n=26) malformations had severe nature. These included absence deformities, musculoskeletal defects, talipes, contracture anomalies and leg defects. It was observed that these anomalies resulted in certain types of restrictions in the normal life functions of the subjects and none of them had undergone cosmetic improvements. Nonetheless, in all the ascertainment categories of recruited subjects , a high male-to-female ratio was observed. A strong sex distortion has been reported in other congenital and hereditary malformations. For instance, in case of talipes, males are twice in proportion as compared to females. malforma9et al.9 in South America, we also observed a preponderance of affected males, low frequency of familial occurrence, involvement of upper limbs more frequently than the lower limbs, and left arm frequently more affected than the right. Furthermore, there were five distinct types of syndactylies in the present study and zygodactyly (OMIM-609815) was observed to be the most common type. Zygodactyly has been observed to be the most common type in several independent epidemiological studies with a prevalence of 2-3/10,000.5There were nine major classes of MLDs in the present sample which could be further categorized into 20 sub-types. In an epidemiological study in Southern Pakistan, nine major types of MLDs were witnessed, and polydactyly and syndactyly were the most common malformations.One of the interesting findings of the present study is the highest representation of digit anomalies among the MLDs. Polydactyly, which was overwhelmingly common in this dataset, had mainly sporadic presentations. In an extended cohort of 313 subjects with polydactyly from Pakistan, 65% cases were observed to be sporadic.Chitralis are traditionally conservative and it was difficult to interact with the community without a local resource person familiar with Khower language and their customs. Moreover, the climate is extreme for several months of the year, especially the harsh winter do not allow much economic activity in the area. Because of cultural and religious influences women’s mobility is restricted. Hence, a general epidemiological study focusing all types of hereditary malformations was not possible .This study is the first description of MLDs in the remote and isolated population of Chitral. One of the major advantages of the present study is a sufficiently large and random sample ascertained from 24 different sites. The current study, however, does not provide the true prevalence and incidence rates of limb anomalies which could be useful in estimating the frequencies of mutation(s) and heterozygote(s) in the populations. Moreover, this study highlights a significant proportion of MLDs cases which have sporadic and isolated nature, and warrants further case-control studies in order to dissect the potential genetic and environmental causes.


High-quality bowel preparation is necessary for colonoscopy. A few studies have been conducted to investigate improvement in bowel preparation quality through patient education. However, the effect of patient education on bowel preparation has not been well studied.A randomized and prospective study was conducted. All patients received regular instruction for bowel preparation during a pre-colonoscopy visit. Those scheduled for colonoscopy were randomly assigned to view an educational video instruction (video group) on the day before the colonoscopy, or to a non-video (control) group. Qualities of bowel preparation using the Ottawa Bowel Preparation Quality scale (Ottawa score) were compared between the video and non-video groups. In addition, factors associated with poor bowel preparation were investigated.P < 0.001) and had good bowel preparation for colonoscopy . Multivariate analysis revealed that males , diabetes mellitus patients , and non-use of visual aids  were associated with poor bowel preparation. In the comparison of the colonoscopic outcomes between groups, the polyp detection rate was not significantly different between video group and non-video group , but insertion time was significantly short in video group (5.5 ± 3.2 min) than non-video group .A total of 502 patients were randomized, 250 to the video group and 252 to the non-video group. The video group exhibited better bowel preparation  than the non-video group  contains supplementary material, which is available to authorized users. Colonoscopy is an important modality for diagnosing and preventing colorectal cancer . AdequatPatient education programs are used in many gastroenterology units to prepare patients for colonoscopy, and a few studies have reported that patient education led to improvements in the quality of colonoscopy preparation, by enhancing patient compliance , 10. In We designed a simple bowel preparation video for patients about to undergo colonoscopy with an emphasis on the importance of adhering to instructions for proper bowel preparation. The video consisted of pictorial demonstrations, subtitles, and simplified instructions. The aim of this study was to measure the effect of this simple video on the quality of bowel preparation during colonoscopy and its impact on clinically relevant outcomes, such as polyp detection. In addition, we investigated factors associated with poor bowel preparation.This study was conducted from October 2014 to February 2015. We enrolled outpatients over 18 years of age undergoing a screening colonoscopy at the endoscopy center of Inha University Hospital. Patients with inflammatory bowel disease, colorectal malignancy, or infectious colitis, prior colonic resection, non-polyethylene glycol solution-based bowel preparation, and/or a family history of colorectal neoplasia were excluded. Patients who had insufficient intellectual capacity to understand the survey process were also excluded. All enrolled patients visited at the endoscopy center and provided written informed consent after receiving explanations about colonoscopy by the endoscopy center staff. Patients were randomized to either the video group or the control group by a random-number generator at the time of colonoscopy scheduling.All patients received regular instructions at the time of their appointment to discuss the colonoscopy. One gastrointestinal staff provided education about colonoscopy, including the exact preparation instructions and information on the importance of bowel preparation and the adverse effects of the agents used. Patients also received a preparation manual with clear written instructions. Patients were prescribed polyethylene glycol electrolyte powder  for bowel preparation. All patients were instructed to end their regular meal before 18:00 and allowed to drink only clear water after regular meal. They were asked to drink two sachets of Coolprep powder dissolved in one liter of water within 60 min at 20:00–21:00 the day before the colonoscopy, as a bowel purgative. They were asked to drink the solution again in the same way at 06:00–07:00 on the day of colonoscopy. Patients were encouraged to drink more clear liquids after purgatives for adequate hydration before colonoscopy. All enrolled patients were scheduled for a morning session (before 13:00).We designed a 6-min bowel preparation video, which included instructions with pictures, video, and subtitles to supplement the standard written preparation instructions. It also included photographs of optimal and poor preparation for patients to visually understand the clinical significance of bowel preparation Fig. . The eduThe study followed a prospective, randomized controlled design. The colonoscopy-performing physician and members of the research team were blinded to the allocation. On the day of colonoscopy, all enrolled patients were asked to complete a three-page multiple choice questionnaire in Korean before the procedure. It included questions evaluating educational level, income level, demographic information (age and sex), previous colonoscopy history, and health behavior . The questionnaire also confirmed whether a patient assigned to the video group watched the educational video. Endoscopists were instructed not to ask patients whether they had viewed the educational video. Colonoscopies were carried out by one of four endoscopists, each of whom had a minimum experience of 1000 colonoscopies and all of them were educated for a week by the typical images of the Ottawa Bowel Preparation Quality Scale (Ottawa score) before the starting study . After tThe study protocol and amendment were approved by the Institutional Review Board of Inha university hospital (IUH-IRB 14-2262). The informed consent of the study was obtained from all patients. The methods of current study adhered to CONSORT guidelines.Poor bowel preparation was defined by total Ottawa score ≥6 at the time of colonoscopy. The insertion time was defined as the interval between the start of the procedure and arrival at the cecum with identification of the appendiceal orifice. Withdrawal time was defined as the interval between withdrawal from the cecum and removal of the colonoscope from the patient.The primary outcome of this study was the quality of bowel preparation as assessed by the endoscopist using the Ottawa score. Secondary outcomes were colonoscope insertion and withdrawal time and the number of polyps and adenomas detected during colonoscopy. We also performed a secondary analysis of demographic information, education level, income, and any previous colonoscopies.A sample size was calculated to obtain a satisfactory estimation with a significance level (α) of 0.05, a power of 80 % with a two-tailed test, and an expected 10 % difference in the rate of colonic cleansing. The expected 10 % difference was based on a previous published study on the efficacy of education for bowel preparation . In the t-test, and the chi-square test was used for categorical variables. The two groups’ bowel preparation scores were compared using the chi-square test. A logistic regression model was used to assess factors associated with poor bowel preparation (Ottawa score ≥6). The odd ratios (OR) and 95 % confidence intervals (95 % CI) were determined. A P value <0.05 was considered statistically significant. Statistical analysis was performed using SPSS .On the baseline characteristics analysis, continuous data were calculated using Student’s n = 252) and the control group (n = 250) . Except the age, the two groups had similar baseline characteristics, including sex, body mass index, history of previous colonoscopy, health behaviors , education level, economic level, and previous abdominal operation history . Using the individual components of the Ottawa score, the video group had better ratings for cleanliness for the right colon, mid colon, and recto-sigmoid. However, the fluid level was not significantly different (P = 0.203). Additionally, the proportion of patients who achieved adequate preparation  differed significantly between the non-video group (78.5 %) and the video group   diabetes mellitus , and no educational video viewing  were factors significantly associated with poor bowel preparation for colonoscopy. The multivariate analysis revealed that male sex , diabetes mellitus , and no educational video viewing  were factors also significantly associated with poor bowel preparation . A significant difference in insertion time was observed between the control (6.1 ± 3.7 min) and experimental groups . However, no significant difference was found in withdrawal time (Table The polyp detection rate was not significantly different between groups. The rates were 19.0 % 48/252) in the non-video group and 19.2 % (48/250) in video group (8/252 in P = 0.02) [P = 0.43) using the Boston Bowel Preparation Scale [P < 0.001). Furthermore, this educational video was effective to reduce the effort for cecal intubation by providing adequate bowel preparation. In the analysis of procedure times, the insertion time was significantly different between the control group and video groups .The defining characteristics of high-quality colonoscopy are the examination of the entire colon, optimal cleaning of the colon, and endoscopic withdrawal time of 6–10 min from cecum to rectum . In thison Scale . In the The content of the educational video did not differ from the preparation manual received by all patients. However, the quality of preparations in the video group was significantly superior to the non-video group. This result means that conventional preparation manuals might have confused participants and failed to enhance patients’ bowel preparation. In addition, patients may forget key components of the bowel preparation process using the manual, because preparation instructions are often discussed in the outpatient clinic as early as 4 weeks before the procedure. The educational video could make the bowel preparation process more accessible to patient with simple words, illustrations, and video clips. Furthermore, providing a supplemental video convenient to access via the Internet at any time can be beneficial to increase compliance with bowel preparation.The use of an educational video via the Internet has been increasingly used and objectively evaluated in other fields, and some investigators reported the benefit of the video clips as a platform for providing educational videos to the patients –18. TherIn previous studies on factors related to poor bowel preparation, male sex, diabetes mellitus, low education level, and low economic level were associated with poor bowel preparation , 20. TheIn our study, overall polyp detection rates were 19.1 % (96/502). This result was lower than those in previously published studies in which the polyp detection rate was >30 % , 14, 21.Our study has notable strengths. First, it is a well-designed, large-scale, colonoscopist-blinded, prospective, randomized trial. Second, we controlled for factors known to influence bowel preparation quality, such as the species of purgative agent, the timing of purgative administration, and the interval between bowel preparation and colonoscopy start time. However, our study has certain limitations. First, it was a community-based, single center study with enrolled patients representing the local residents of Incheon. Therefore, the participants might not represent the general population. In addition, the inter-endoscopist agreement for the Ottawa score was not validated in this study. Thus, there would be a risk of inter-observer bias in current study. Second, the effect of the educational video alone was not evaluated in current study. The educational video was used as a complementary preparation method in current study, so that further study would be needed to confirm the true effect of educational video alone for bowel preparation. Finally, our study only evaluated preparation quality with a single preparation method and did not compare other available preparation products and processes.In conclusion, an educational video might increase the quality of bowel preparation and decrease colonoscopists’ effort for cecal intubation. In addition, male sex and diabetes mellitus are significant risk factors for poor bowel preparation. Further studies with variable patient demographics and different preparation processes may be useful to evaluate the impact of an education video on bowel preparation.OR, Odd ratio; Ottawa score, Ottawa Bowel Preparation Quality Scale.


Beilstein Journal of Organic Chemistry on natural products in 2011 and 2013 [Artemisia annua [Streptomyces avermitilis at the famous Kitasato Institute and for the development of derivatives that are used as highly potent anthelmintics both for animal and human welfare [As a continuation of the first two Thematic Series in the  welfare . Current welfare ), analyt welfare , gene sy welfare  offer an welfare  continueBeilstein Journal of Organic Chemistry and also the whole team at the Beilstein-Institut for their professional work. I wish the readers of the present Thematic Series joyful reading and hopefully new inspiration for their own research.I thank all contributors that participated in this third Thematic Series on natural product chemistry in the Jeroen S. DickschatBonn, February 2016