BACKGROUND & AIMS: :We introduce a family of positive definite kernels specifically optimized for the manipulation of 3D structures of molecules with kernel methods. The kernels are based on the comparison of the three-point pharmacophores present in the 3D structures of molecules, a set of molecular features known to be particularly relevant for virtual screening applications. We present a computationally demanding exact implementation of these kernels, as well as fast approximations related to the classical fingerprint-based approaches. Experimental results suggest that this new approach is competitive with state-of-the-art algorithms based on the 2D structure of molecules for the detection of inhibitors of several drug targets.

背景与目标： : 我们介绍了一系列正定核，这些核专门针对使用核方法操纵分子的3D结构进行了优化。内核基于分子3D结构中存在的三点药效团的比较，这是一组已知与虚拟筛选应用特别相关的分子特征。我们提出了对这些内核的计算要求很高的精确实现，以及与经典的基于指纹的方法相关的快速逼近。实验结果表明，这种新方法与基于分子2D结构的最新算法具有竞争力，可用于检测几种药物靶标的抑制剂。

BACKGROUND & AIMS: OBJECTIVES:To evaluate screening for retinopathy of prematurity (ROP) in Sweden and to investigate possible modifications of the present screening guidelines. METHODS:Infants in Sweden with a gestational age (GA) of 31 weeks + 6 days or less are screened for ROP. Data from the Swedish national register for ROP (SWEDROP) during 2008 and 2009 were extracted and compared with a national perinatal quality register. RESULTS:In SWEDROP, there were 1791 infants born before a GA of 32 weeks from January 1, 2008, through December 31, 2009. Another 70 infants were registered in the perinatal quality register but not in SWEDROP (dropout rate, 3.8% [70 of 1861 infants]). Seven infants died before termination of screening. In the final study cohort (1784 infants), 15.6% had mild ROP and 8.5% had severe ROP. Treatment was performed in 4.4% of the infants, none of whom had a GA at birth of more than 28 weeks. Nine infants with a GA of more than 28 weeks at birth developed stage 3 ROP, which regressed spontaneously. The total number of examinations was 9286 (964 in infants with a GA of 31 weeks), and the mean (range) number of examinations of each infant was 5.2 (1-30). CONCLUSIONS:The SWEDROP, a quality register for ROP, has a national coverage (ie, participation) of 96%. Data from 2008 to 2009 show that it seems possible to reduce the upper limit for screening in Sweden by 1 week, including only infants with a GA of 30 weeks + 6 days or less. However, such a change should be combined with a strong recommendation to neonatologists to refer also severely ill and more "mature" infants.

背景与目标：

BACKGROUND & AIMS: :In the present pilot study, the feasibility of a site-of-care cervicovaginal self-sampling methodology for HPV-based screening was tested in 346 women residing in underserved rural areas of Northern Greece. These women provided self-collected cervicovaginal sample along with a study questionnaire. Following molecular testing, using the cobas® HPV Test, Roche®, HPV positive women, were referred to colposcopy and upon abnormal findings, to biopsy and treatment. Participation rate was 100%. Regular pap-test examination was reported for 17.1%. Among hrHPV testing, 11.9% were positive and colposcopy/biopsy revealed 2 CIN3 cases. Non-compliance was the most prevalent reason for no previous attendance. Most women reported non-difficulty and non-discomfort in self-sampling (77.6% and 82.4%, respectively). They would choose self-sampling over clinician-sampling (86.2%), and should self-sampling being available, they would test themselves more regularly (92.3%). In conclusion, self-sampling is feasible and well-accepted for HPV-based screening, and could increase population coverage in underserved areas, helping towards successful prevention.

背景与目标： : 在本试点研究中，对居住在希腊北部服务不足的农村地区的346名妇女进行了基于HPV筛查的护理现场宫颈阴道自采样方法的可行性进行了测试。这些妇女提供了自我收集的宫颈阴道样本以及研究问卷。在分子测试之后，使用cobas®罗氏HPV检测®HPV阳性女性被转诊至阴道镜检查和异常发现后，进行活检和治疗。参与率为100%。报告定期进行17.1% 巴氏试验检查。在hrHPV检测中，11.9% 例为阳性，阴道镜/活检显示2例CIN3。不遵守是以前没有出席的最普遍原因。大多数妇女报告说，自我取样没有困难，也没有不适 (分别为77.6% 和82.4%)。他们将选择自采样而不是临床医生采样 (86.2%)，并且如果自采样可用，他们将更定期地测试自己 (92.3%)。总之，自我采样对于基于HPV的筛查是可行的且被广泛接受，并且可以增加服务不足地区的人口覆盖率，从而有助于成功预防。

BACKGROUND & AIMS: OBJECTIVE:Unidentified hearing loss at birth can adversely affect speech and language development as well as academic achievement and social-emotional development. Historically, moderate-to-severe hearing loss in young children was not detected until well beyond the newborn period. Around 0.5 to 5 in every 1000 neonates and infants have congenital or early childhood onset sensorineural hearing impairment. When identification and intervention occur at no later than 6 months of age, the infants perform much higher on school-related measures. Therefore, early detection is vitally important. Toward the end of 2009, the Israeli ministry of health issued a directive establishing a universal newborn hearing screening program in all hospitals in the country from 01.01.10. The objectives of this study are to evaluate a newly established universal newborn hearing screening program, to assess performance and to compare measurements of performance to performance benchmarks representing a consensus of expert opinion. The benchmarks are the minimal requirements that should be attained by high-quality early hearing detection programs. METHODS:As specified by the ministry of health, a two-stage screening protocol was implemented using otoacoustic emissions and automated auditory brainstem response. Screening results of all neonates born from the initiation of the program on 15th March 2010 until the end of 2011 were reviewed. RESULTS:The total number of live births during the study period was 5496. Of these, 5334 (97%) started screening for hearing loss but only 5212 completed the screening process, giving a screening coverage of 94.8%. Of the 5212 neonates completing the screening process, 270 (5.18%) were referred for full diagnostic testing. CONCLUSIONS:The newly established universal newborn hearing screening program at the Ziv Medical Center in Zefat closely approaches, but does not yet meet the minimal requirements that should be attained by high-quality early hearing detection programs. Every effort should be made to complete the screening tests before discharge from hospital. Screening staff should actively encourage parents to participate in all stages of early detection.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:We modified and reconstructed a high image quality portable non-mydriatic fundus camera and compared it with the tabletop fundus camera to evaluate the efficacy of the new camera in detecting retinal diseases. METHODS:We designed and built a novel portable handheld fundus camera with telemedicine system. The image quality of fundus cameras was compared to that of existing commercial tabletop cameras by taking photographs of 364 eyes from the 254 patients. In all 800 fundus images taken by two camera types, 400 images per camera, were graded with the four image clarity classifications. RESULTS:Using the portable fundus camera, 63% (252/400) images were graded as excellent overall quality, 20.5% (82/400) were good, 11.75% (47/400) were fair, and 4.75% (19/400) were inadequate. Using the tabletop fundus camera, 70.75% (283/400) images were graded as excellent overall quality, 20.4% (51/400) were good, 13.25% (53/400) were fair, and 3.25% (13/400) were inadequate. Common retinal diseases were easily identified from fundus images obtained from the portable fundus camera. CONCLUSION:The new type of non-mydriatic portable fundus camera was qualified to have professional quality of fundus images. The revolutionary screening camera provides a foundational platform which can potentially improve the accessibility of retinal screening programmes.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:The penetrance of hypertrophic cardiomyopathy (HCM) during childhood and adolescence has been only sparsely described. We studied the penetrance of HCM and the short- and long-term outcomes of clinical screening and predictive genetic testing of child relatives of patients with HCM. METHODS AND RESULTS:Ninety probands and 361 relatives were included in a family screening program for HCM (1994-2001). Eleven sarcomere genes, CRYAB, α-GAL, and titin were screened. Sixty-six relatives and 4 probands were <18 years of age at inclusion. Twelve child relatives were mutation carriers (age, 12 ± 5 years), and 26 had unknown genetic status, ie, relatives from families without identified mutations (n = 21) or not tested (n = 5) (age, 11 ± 5 years). Twenty-eight noncarriers (42%; age, 10 ± 4 years) served as control subjects. Two of 38 child relatives (5%) at risk of developing HCM fulfilled diagnostic criteria for HCM at inclusion. After 12 ± 1 years of follow-up, 2 of the 36 (6%; 95% confidence interval, 2-18) at-risk child relatives who were phenotype negative at inclusion had developed the HCM phenotype at 26 and 28 years of age. During follow-up, none of the child relatives experienced serious cardiac events. Participation in the screening program had no long-term negative psychological impact. CONCLUSIONS:The penetrance of HCM in phenotype-negative child relatives at risk of developing HCM was 6% after 12 years of follow-up. The finding of phenotype conversion in the mid-20s warrants continued screening into adulthood. Forty-two percent of the child relatives were noncarriers, and repeat clinical follow-up could be safely limited to the remaining children.

背景与目标：

BACKGROUND & AIMS: :Cervical screening attendance among women aged 25-29 years in England is lower than at older ages. There is some evidence that pre-notification leaflets motivate women who have not yet considered their response to a health intervention. We aimed to identify key information to motivate young women at their first cervical screening invitation. Six focus groups were conducted, five with young women aged 17-25 registered with a General Practice in Manchester, UK, and one with Practice nurses. Some women took part in two further groups to discuss leaflet design. There was low awareness of the purpose or procedures of cervical screening, and most women were de-motivated by reports of bad experiences. Some intended to be screened, but not immediately after invitation. Screening was viewed as a test for a cancer that affected older women. Since none of the participants believed that they had cervical cancer, screening seemed unnecessary. We conclude that the perception that screening is unimportant when you are young needs to be challenged. Women also need to be better informed of screening procedures. A pre-notification leaflet incorporating key information was designed and will be tested in a randomized trial of complex interventions within the routine cervical screening programme.

背景与目标： : 英格兰25-29岁女性的子宫颈筛查出勤率低于老年人。有证据表明，预先通知的传单会激励尚未考虑对健康干预措施做出反应的妇女。我们的目标是确定关键信息，以激励年轻女性首次接受子宫颈筛查邀请。进行了六个重点小组，其中五个是在英国曼彻斯特注册的17-25岁的年轻女性，其中一个是执业护士。一些妇女参加了另外两个小组，讨论传单设计。人们对宫颈筛查的目的或程序的认识不足，大多数妇女因不良经历的报道而缺乏动力。有些人打算放映，但不是在邀请后立即放映。筛查被视为对影响老年妇女的癌症的测试。由于没有参与者相信自己患有宫颈癌，因此筛查似乎没有必要。我们得出的结论是，年轻时筛查不重要的看法需要受到挑战。妇女还需要更好地了解筛查程序。设计了包含关键信息的预通知传单，并将在常规子宫颈筛查计划中进行复杂干预的随机试验中进行测试。

BACKGROUND & AIMS: JUSTIFICATION:Hearing impairment is one of the most critical sensory impairments with significant social and psychological consequences. Evidence-based, standardized national guidelines are needed for professionals to screen for hearing impairment during the neonatal period. PROCESS:The meeting on formulation of national consensus guidelines on developmental disorders was organized by Indian Academy of Pediatrics in Mumbai, on 18th and 19th December, 2015. The invited experts included Pediatricians, Developmental Pediatricians, Pediatric Neurologists and Clinical Psychologists. The participants framed guidelines after extensive discussions. OBJECTIVE:To provide guidelines on newborn hearing screening in India. RECOMMENDATIONS:The first screening should be conducted before the neonate's discharge from the hospital - if it 'fails', then it should be repeated after four weeks, or at first immunization visit. If it 'fails' again, then Auditory Brainstem Response (ABR) audiometry should be conducted. All babies admitted to intensive care unit should be screened via ABR. All babies with abnormal ABR should undergo detailed evaluation, hearing aid fitting and auditory rehabilitation, before six months of age. The goal is to screen newborn babies before one month of age, diagnose hearing loss before three months of age and start intervention before six months of age.

背景与目标：

BACKGROUND & AIMS: :Plants from Suriname (South-America) and several Annona species, including A. muricata, A. ckerimolia, A. montana and A. glabra were screened for 5-HT(1A) receptor binding activity by ligand-binding-studies (LBS). Crude extracts of all Annona species and from Hibiscus bifurcatus, Irlbarchia purpurascens and Scoparia dulcis showed high activity. The isoquinoline alkaloids asimilobine (1), nornuciferine (2), and annonaine (3) were isolated as the active principles from the fruit of Annona muricata. These results may partially explain the use of Hibiscus bifurcatus and Annona muricata in traditional medicine in Suriname.

背景与目标： : 通过配体结合研究 (LBS) 筛选了苏里南 (南美) 的植物和几种番荔叶物种，包括A. muricata，A. ckerimolia，A. montana和A. glabra的5-HT(1A) 受体结合活性。所有番荔叶物种的粗提物以及木槿，紫菜和紫菜的粗提物均显示出很高的活性。从番荔叶果实中分离出异喹啉生物碱asimilobine (1)，去甲钙碱 (2) 和番荔碱 (3) 作为活性成分。这些结果可能部分解释了苏里南传统医学中芙蓉和番荔叶的使用。

BACKGROUND & AIMS: BACKGROUND:Although the Kinect gaming system (Microsoft Corp, Redmond, WA) has been shown to be of therapeutic benefit in rehabilitation, the applicability of Kinect-based virtual reality (VR) training to improve motor function following a stroke has not been investigated. This study aimed to investigate the effects of VR training, using the Xbox Kinect-based game system, on the motor recovery of patients with chronic hemiplegic stroke. METHODS:This was a randomized controlled trial. Twenty patients with hemiplegic stroke were randomly assigned to either the intervention group or the control group. Participants in the intervention group (n = 10) received 30 minutes of conventional physical therapy plus 30 minutes of VR training using Xbox Kinect-based games, and those in the control group (n = 10) received 30 minutes of conventional physical therapy only. All interventions consisted of daily sessions for a 6-week period. All measurements using Fugl-Meyer Assessment (FMA-LE), the Berg Balance Scale (BBS), the Timed Up and Go test (TUG), and the 10-meter Walk Test (10mWT) were performed at baseline and at the end of the 6 weeks. RESULTS:The scores on the FMA-LE, BBS, TUG, and 10mWT improved significantly from baseline to post intervention in both the intervention and the control groups after training. The pre-to-post difference scores on BBS, TUG, and 10mWT for the intervention group were significantly more improved than those for the control group (P <.05). CONCLUSIONS:Evidence from the present study supports the use of additional VR training with the Xbox Kinect gaming system as an effective therapeutic approach for improving motor function during stroke rehabilitation.

背景与目标：

BACKGROUND & AIMS: :Flying phobia is a problem that affects a significant portion of the population. There are a number of therapeutic approaches but no one is universally accepted as the gold standard. One therapy is hypnosis. A recent addition to the armamentarium is virtual reality exposure (VRE) therapy. Both therapies are short-term and compare favorably to in vivo desensitization. Heretofore a combination of both approaches has not been reported. This article presents a case of a 50-year phobia to flying that was refractory to traditional methods including pharmacotherapy, systematic desensitization, and cognitive behavioral therapy but was successfully treated using VRE therapy and hypnosis as the primary modalities. This treatment was supplemented by other approaches. The rationale for this multimodal therapy and possible mechanisms involved are discussed.

背景与目标： : 飞行恐惧症是一个影响很大一部分人口的问题。有许多治疗方法，但没有人被普遍接受为黄金标准。一种疗法是催眠。最近在aramentarium中添加的是虚拟现实暴露 (VRE) 疗法。两种疗法都是短期的，与体内脱敏相比是有利的。迄今为止，尚未报道两种方法的组合。本文介绍了一个50年的飞行恐惧症案例，该案例对传统方法 (包括药物疗法，系统脱敏和认知行为疗法) 难以治疗，但已成功使用VRE疗法和催眠作为主要方式进行治疗。这种治疗得到了其他方法的补充。讨论了这种多模式疗法的原理和可能的机制。

BACKGROUND & AIMS: Thirteen cultivars of hop (Humulus lupulus L.) were tested by reverse transcription-polymerase chain reaction (RT-PCR) for the presence of apple mosaic virus (ApMV). The virus was detected in various amounts in all tested cultivars. Control hop clones derived from tissue cultures, treated by thermotherapy and maintained in greenhouse were virus-free. The procedure for sample preparation and RT-PCR of ApMV is described in detail.

背景与目标： 通过逆转录聚合酶链反应 (rt-pcr) 测试了13个啤酒花品种 (Humulus lupulus L.) 是否存在苹果花叶病毒 (ApMV)。在所有测试品种中均检测到不同数量的病毒。来自组织培养物的对照啤酒花克隆，通过热疗处理并保存在温室中，无病毒。详细介绍了ApMV的样品制备和rt-pcr程序。

BACKGROUND & AIMS: :Screening programs can reduce the burden of disease, however, they can be associated with raised levels of anxiety. The risk of endometrial and ovarian cancer is increased in hereditary nonpolyposis colorectal cancer (HNPCC). There is no prospective evidence to support screening for gynecological disease in HNPCC, however, current recommendations include the use of ultrasound and endometrial biopsy. This study assesses the impact of screening for gynecological cancer on self-reported symptoms of anxiety, depression, and perceptions of health. Women from HNPCC families attending gynecological screening (n = 26) completed the Hospital Anxiety and Depression Scale and the ShortForm36v2 questionnaires prior to screening with transvaginal ultrasound, outpatient/office hysteroscopy, endometrial biopsy, and ovarian tumor marker assessment (CA125). The same questionnaires were completed at 3 and 6 months following screening (15/26). Women in HNPCC families attending for gynecological screening did not have excess symptoms of anxiety or depression at baseline in subjective comparison to other populations. The process of screening and false positive screening results had no significant impact on symptoms of anxiety and depression or perceptions of health. We conclude that within the limitations of analysis in this small study group, screening for gynecological disease in HNPCC does not appear to be associated with any psychological morbidity.

背景与目标： : 筛查计划可以减轻疾病负担，但是，它们可能与焦虑水平升高有关。遗传性非息肉病性结直肠癌 (HNPCC) 发生子宫内膜癌和卵巢癌的风险增加。目前尚无前瞻性证据支持在HNPCC中筛查妇科疾病，但是，目前的建议包括使用超声和子宫内膜活检。这项研究评估了筛查妇科癌症对自我报告的焦虑，抑郁和健康观念的影响。来自HNPCC家庭的女性 (n = 26) 在接受经阴道超声，门诊/办公室宫腔镜检查，子宫内膜活检和卵巢肿瘤标志物评估 (CA125) 进行筛查之前，完成了医院焦虑和抑郁量表和ShortForm36v2问卷。在筛选后的3个月和6个月 (15/26) 完成相同的问卷。与其他人群相比，参加妇科筛查的HNPCC家庭中的女性在基线时没有过度的焦虑或抑郁症状。筛查过程和假阳性筛查结果对焦虑抑郁症状或健康感知无显著影响。我们得出的结论是，在这个小型研究组的分析局限性内，在HNPCC中筛查妇科疾病似乎与任何心理疾病无关。

BACKGROUND & AIMS: :Factor V(Leiden) is the most common abnormality detected in patients examined because of hereditary thrombophilia. The most widely used clot-based screening test is based on the activated partial thromboplastin (aPTT) time. This test has a low sensitivity. A comparison of the aPTT-based test with a Russell viper venom time test (RVVT) was performed in matched samples. All samples were analyzed by polymerase chain reaction (PCR) for the factor V(Leiden) defect. We studied 139 samples, of which 109 were PCR-negative; 30 were PCR-positive. Using the manufacturer's suggested threshold ratio of 2, the aPTT test showed a sensitivity of 0.43, a specificity of 0.86, and a positive predictive value (PPV) of 0.97. The RVVT test had a sensitivity of 1.0, a specificity of 0.95, and a PPV of 0.91. Segregation of a subpopulation of this study population into ABO group O vs non-group O showed an effect of ABO group on the aPTT test but not on the RVVT test, consistent with an influence of factor VIII clotting (factor VIII:C) on the aPTT test. The RVVT test seems superior to the unmodified aPTT test as a screening test for factor V(Leiden).

背景与目标： : 因子V(Leiden) 是由于遗传性血栓形成而在检查的患者中最常见的异常。最广泛使用的基于凝块的筛查测试是基于活化的部分凝血活酶 (aPTT) 时间。该测试灵敏度低。在匹配的样品中进行了基于aPTT的测试与Russell viper毒液时间测试 (RVVT) 的比较。所有样品均通过聚合酶链反应 (PCR) 分析因子V (莱顿) 缺陷。我们研究了139份样品，其中109份为PCR阴性; 30份为PCR阳性。使用制造商建议的阈值比率2，aPTT测试显示出0.43的敏感性，0.86的特异性和0.97的阳性预测值 (PPV)。RVVT测试的敏感性为1.0，特异性为0.95，PPV为0.91。将该研究人群的亚群分为ABO组O和非O组，显示ABO组对aPTT测试有影响，但对RVVT测试没有影响，这与因子VIII凝血 (因子VIII:C) 的影响一致aPTT测试。作为因子V(Leiden) 的筛选测试，RVVT测试似乎优于未修改的aPTT测试。

BACKGROUND & AIMS: :We have examined maternal urine concentrations of beta core, free beta human chorionic gonadotrophin (hCG), and total oestriol in 373 control pregnancies and 43 pregnancies affected by aneuploidy (including 22 cases of Down's syndrome) in an attempt to see if any of the analytes have a value in Down's syndrome screening between the tenth and 14th week of pregnancy. We have compared the performance of these analytes against nuchal translucency measurement combined with maternal serum free beta hCG at the same period of pregnancy. Our results show that levels of urine free beta hCG and beta core are increased in Down's syndrome with average multiple of the median levels of 1.81 and 2.91, respectively. Urine total oestriol was reduced (0.83) whilst maternal serum free beta hCG was increased (1.72). In trisomy 18 the levels of all analytes were reduced, although serum free beta hCG was the most discriminating. The spread of results in the control and the Down's group for urine beta core was more than three times than that for serum free beta hCG and with urine free beta hCG it was two times wider. In combination with maternal age, urine total oestriol had a 32 per cent detection rate at a fixed 5 per cent false-positive rate; urine beta core 34 per cent, urine free beta hCG 36 per cent, maternal serum free beta hCG 44 per cent, and nuchal translucency 82 per cent. In combination with nuchal translucency, urine total oestriol added an extra 1 per cent detection, urine beta core an extra 2 per cent, urine free beta hCG an extra 3 per cent, and serum free beta hCG an extra 5 per cent. It is unlikely that any of the urine markers will be of value in first-trimester screening. Optimal first-trimester screening programmes will rely for the foreseeable future on nuchal translucency, serum free beta hCG, and possibly pregnancy-associated plasma protein A.

背景与目标： : 我们检查了母体尿液中 β 核心，游离 β 人绒毛膜促性腺激素 (hCG) 的浓度，以及373例对照妊娠和43例受非整倍性影响的妊娠 (包括22例唐氏综合征) 中的总雌三醇，试图在妊娠的第十周至第14周之间查看任何分析物在唐氏综合征筛查中是否具有价值。我们已经比较了这些分析物在妊娠同一时期与胎儿透明层测量结合母体血清游离 β hCG的性能。我们的结果表明，在唐氏综合症中，尿液游离的 β hCG和 β 核心水平分别增加了平均1.81和2.91水平的倍数。尿总雌三醇减少 (0.83)，而母体血清游离 β-hCG增加 (1.72)。在18三体中，所有分析物的水平都降低了，尽管无血清 β-hCG是最有区别的。在对照组和唐氏组中，尿液 β 核心的结果传播是血清游离 β hCG的三倍以上，而尿液游离 β hCG的传播是其两倍。结合产妇年龄，尿总雌三醇检出率为32%，假阳性率固定为5%; 尿 β 核心34%，尿游离 β hCG 36%，母血清游离 β hCG 44%，颈项半透明82%。结合颈项半透明性，尿液总雌三醇额外增加了1% 的检测，尿液 β 核额外增加了2%，尿液游离 β hCG额外增加了3%，血清游离 β hCG额外增加了5%。在孕早期筛查中，任何尿液标志物都不太可能具有价值。在可预见的将来，最佳的孕早期筛查计划将依赖于颈项透明层，血清游离 β hCG以及可能与妊娠相关的血浆蛋白A。