Divyansh Agarwal, Jingshu Wang, Nancy R. Zhang.

Source: Statistical Science, Volume 35, Number 1, 112--128.

Abstract:
Single cell sequencing technologies are transforming biomedical research. However, due to the inherent nature of the data, single cell RNA sequencing analysis poses new computational and statistical challenges. We begin with a survey of a selection of topics in this field, with a gentle introduction to the biology and a more detailed exploration of the technical noise. We consider in detail the problem of single cell data denoising, sometimes referred to as “imputation” in the relevant literature. We discuss why this is not a typical statistical imputation problem, and review current approaches to this problem. We then explore why the use of denoised values in downstream analyses invites novel statistical insights, and how denoising uncertainty should be accounted for to yield valid statistical inference. The utilization of denoised or imputed matrices in statistical inference is not unique to single cell genomics, and arises in many other fields. We describe the challenges in this type of analysis, discuss some preliminary solutions, and highlight unresolved issues.

London (33 Stillness Road, London SE23 ING) : Cleanair, [198-?]

Hedok Lee
Aug 5, 2015; 35:11034-11044
Neurobiology of Disease

KM Harris
Jul 1, 1992; 12:2685-2705
Articles

JS Taube
Feb 1, 1990; 10:420-435
Articles

Chris Englund
Jan 5, 2005; 25:247-251
BRIEF COMMUNICATION

Guo-qiang Bi
Dec 15, 1998; 18:10464-10472
Articles

Spanish translation of the BIS press release about the BIS Quarterly Review, March 2019

Story: Several apostles affiliated with the movement helped organize or spoke at Rick Perry's recent prayer rally. A leading apostle, C. Peter Wagner, talks about the movement and its missions, which include acquiring leadership positions in government, the media, and arts and entertainment.

Dopaminergic neurons innervate extensive areas of the brain and release dopamine (DA) onto a wide range of target neurons. However, DA release is also precisely regulated. In Drosophila melanogaster brain explant preparations, DA is released specifically onto α3/α'3 compartments of mushroom body (MB) neurons that have been coincidentally activated by cholinergic and glutamatergic inputs. The mechanism for this precise release has been unclear. Here we found that coincidentally activated MB neurons generate carbon monoxide (CO), which functions as a retrograde signal evoking local DA release from presynaptic terminals. CO production depends on activity of heme oxygenase in postsynaptic MB neurons, and CO-evoked DA release requires Ca²⁺ efflux through ryanodine receptors in DA terminals. CO is only produced in MB areas receiving coincident activation, and removal of CO using scavengers blocks DA release. We propose that DA neurons use two distinct modes of transmission to produce global and local DA signaling.

SIGNIFICANCE STATEMENT Dopamine (DA) is needed for various higher brain functions, including memory formation. However, DA neurons form extensive synaptic connections, while memory formation requires highly specific and localized DA release. Here we identify a mechanism through which DA release from presynaptic terminals is controlled by postsynaptic activity. Postsynaptic neurons activated by cholinergic and glutamatergic inputs generate carbon monoxide, which acts as a retrograde messenger inducing presynaptic DA release. Released DA is required for memory-associated plasticity. Our work identifies a novel mechanism that restricts DA release to the specific postsynaptic sites that require DA during memory formation.

As FAO launches dedicated webpages on post-2015, here are seven things to know about the process and how FAO is playing its part. 7 - Post-2015 development agenda - The name refers to the process through which Member States agree on a new global development framework to succeed the Millennium Development Goals (MDGs), eight goals that followed the UN Millennium Declaration [...]

The Farmers’ Market has been postponed for Friday 6 March and until further notice.

Delaying the Games for a year is considered by many to be the best course of action for public health

This paper reviews post-crisis financial regulatory reforms, examines how they fit together and identifies open issues. Specifically, it takes stock of the salient new features of bank and CCP international standards within a unified analytical framework.

Hearing of Mr François Villeroy de Galhau, Governor of the Bank of France, before the Section for the Economy and Finance of the French Economic, Social and Environmental Council, Paris, 8 April 2020.

1. Coronavirus Outbreak Updates: Maharashtra reports 1,089 new COVID-19 cases across state, 748 in Mumbai; total infections at 19,063  Firstpost
2. Migrant workers | Maharashtra train accident victims were battling hunger  The Hindu
3. Maharashtra: They thought no trains were running, loco driver spotted them too late to stop  The Indian Express
4. ‘Stay where you are’: Shivraj Chouhan appeals to migrants after train tragedy  Hindustan Times
5. MP Ministers Ask Shivraj to Probe Tenure of Kamal Nath to ‘Expose Massive Corruption’  News18
6. View Full coverage on Google News

India's lavish weddings go online in virus lockdown  South China Morning Post

Bank for International Settlements BIS Working Papers by Claudio Borio, Marc Farag and Nikola Tarashev

Apple's Jeff Williams says that supply chains are running well and that the company is optimistic about the future for the economy both for itself and for America as a whole.

Hailed as transitional by local observers, the latest polls were expected to usher in a new type of leadership in FRELIMO, with Filipe Nyussi being the first non-liberation northern leader in a southern dominated elite; they would also see opposition parties RENAMO and MDM alter their strategies and become more politically relevant; and would possibly be the last polls before the country became a mass resource-producing economy. However, the Presidential and parliamentary elections of 15 October have made the political setting, the prospects for improved governance and wealth redistribution more opaque, and the implementation of the new peace agreement harder.

Congress needs to invest with an eye on the nation’s future.

Vatican City, May 6, 2020 / 11:47 am (CNA).- The annual swearing-in of new Swiss Guards, which would usually take place May 6, was moved to Oct. 4 because of the coronavirus.

Instead, the Pontifical Swiss Guards marked Wednesday’s anniversary of the Sack of Rome with private, more muted celebrations, lacking the presence of guests and streamed over the internet.

The Swiss Guards marked the 493rd anniversary of the May 6, 1527 battle with Mass in the church of Santa Maria of the Pieta in the Teutonic College, followed by the “laying of the wreath,” in the Square of the Roman Protomartyrs in Vatican City.

Afterward, the commander of the Swiss Guards conferred papal honorifics on 15 guards.

After Mass, all but the newest members of the world’s smallest-but-oldest standing army marched to Square of the Roman Protomartyrs, so-named for being the site of the death of several early Christian martyrs, including St. Peter.

The Commander of the Swiss Guards, Christoph Graf, gave a speech at the ceremony in which he recounted the story of the 1527 battle known as the Sack of Rome, when 147 guards lost their lives defending Pope Clement VII from mutinous troops of the Holy Roman Empire.

During the battle, the pope was able to escape from the Vatican to Castel Sant’Angelo via a secret passageway connecting the two. It is the most significant and deadly event in the history of the Swiss Guards.

After the speech, a large wreath was placed in the square in commemoration of the guards who died during the battle.

The anniversary is usually marked by a whole weekend of events attended by representatives of the Swiss army, Swiss government, and Swiss bishops’ conference. Family and friends of the guards, and former guards who return for a visit, also participate.

In past years, the festivities have also included a concert and an audience with Pope Francis.

The main celebrant of the May 6 Mass was the assessor of the Secretariat of State, Msgr. Luigi Roberto Cona. In his homily, Cona said he wishes the guards may “truly experience Christ.”

“May you encounter a Church that is not only an institution, an institution to be defended, to be protected, which you have wisely done for 500 years now, but also a community, a believing community which has met the living and true Christ, which loves him, and intends to serve him in everyday life,” he said.

“Because every day we too, in imitation of the first Christian martyrs – and your brother guards who offered themselves at that very important moment in 1527 – we too, without the heroism of those, can offer ourselves day after day in the services we are called to perform.”

It’s been a nerve-wracking few years for the traditional auto industry. One Silicon Valley VC firm speculates on its future in an interview with Bloomberg.

MAY is normally a busy month behind the scenes for Gareth Chalmers and the ongoing uncertainty around sport hasn’t changed that a huge amount.

Following yesterday´s Supervisory Board meeting and the meeting on 19 March 2020, yesterday´s FBB shareholders’ meeting dealt with the results of the meeting and confirmed its main decisions. The shareholders recognised the business plan approved by th...

In light of the regulations on hygiene and gatherings in connection with the global corona pandemic, a fire safety and evacuation exercise, which was scheduled to take place on 29 April in Terminal T1 and the BER railway station, has been postponed yest...

"Do we sometimes feel uneasy that our business-as-mission and vocation models are so dependent on the very people that we are trying to reach? Does this make us feel powerless and needy?" asks Seang Pin.

HOLIDAYS may be temporarily on hold, but planning magical trips is still possible. Spontaneity shapes thrilling travel escapades, but there's also a case for careful, methodical planning. Often, the preparation – deciding on a route, reading up about a destination – can be just as enjoyable as the trip itself.

The UEFA HatTrick programme has assisted in the construction of over 200 mini-pitches in Portugal since 2007, giving more youngsters the chance to play football in a safe environment.

Childhood gender nonconformity has been associated with poorer relationships with parents, but it is unknown if childhood gender nonconformity is associated with childhood abuse or with posttraumatic stress disorder.

We identify gender nonconformity before age 11 years as a risk indicator for physical, sexual, and psychological abuse in childhood and lifetime probable posttraumatic stress disorder in youth. (Read the full article)

Previous research has identified low rates of employment and postsecondary education for youth with autism, but generalizability has been limited by small samples.

Using national data, the authors of this study found that youth with autism are at high risk for no postsecondary education or employment, especially in the first 2 years after high school. Findings highlight the need for improved transition planning. (Read the full article)

Declining dietary omega 3 polyunsaturated fatty acids has been associated with rising allergy prevalence and fish oil is therefore of interest in allergy prevention. Supplementation during pregnancy, but not after the age of 6 months, has achieved some allergy reductions.

We assessed the effect of fish oil supplementation from birth to 6 months, which has not been investigated previously. Our results, together with previous findings, will likely help define a "window of opportunity" for allergy intervention using fish oil supplements. (Read the full article)

Guidelines encourage pediatric health care providers to aid in identifying women with postpartum depression but not postpartum anxiety, yet the major life event of childbirth can be anxiety provoking for many women.

During the postpartum hospital stay, anxiety was far more common than depression among breastfeeding women. Anxiety remained more common for the 6 months after childbirth, and was associated with increased health care use and reduced breastfeeding duration, particularly among primiparous women. (Read the full article)

Studies reveal that mothers of infants with colic (defined by Wessel’s criteria of >3 hours per day of distress) are more likely to develop depression. No studies have examined whether the consolability of infant crying predicts maternal depression risk.

Prolonged inconsolable infant crying has a stronger association with maternal depressive symptoms than overall daily duration of fussing and crying, suggesting that a mother’s report of inability to soothe her infant may be a powerful indicator of her depression risk. (Read the full article)

Infants aged <2 months are at highest risk for pertussis morbidity and mortality but are too young to receive pertussis vaccines. To protect young infants, the Advisory Committee on Immunization Practices recommends mothers receive 1 dose of Tdap during pregnancy.

This article evaluates the effect of Tdap during pregnancy compared with postpartum Tdap and cocooning in preventing infant pertussis cases, hospitalizations, and deaths, as well as their relative cost-effectiveness. (Read the full article)

Although most US mothers initiate breastfeeding, half fail to achieve their breastfeeding intentions. In cross-sectional and retrospective surveys, early breastfeeding difficulties are often cited as reasons for stopping breastfeeding earlier than intended.

We characterized 4179 breastfeeding concerns/problems as reported by primiparas interviewed prospectively. Concerns were highly prevalent and associated with up to ninefold greater risk of stopping breastfeeding earlier than intended. Concerns at 3 to 7 days posed the greatest risk. (Read the full article)

Better postnatal growth, especially head growth, associates with better cognitive development in preterm infants. Suboptimal postnatal growth is more common in infants with poor antenatal growth than in infants with normal growth.

Good weight gain and head circumference growth until 2 years was associated with better 5-year cognitive outcome in non–small for gestational age infants. Good head circumference growth around term age benefits the cognitive outcome of small for gestational age infants. (Read the full article)

Studies assessing the accuracy of brief screening tools for postpartum depression have been conducted among adult women; however, no similar validation studies have been conducted among adolescent mothers. Accurate and valid brief depression screening tools are needed for adolescent mothers.

We found that the 10-item Edinburgh Postnatal Depression Scale (EPDS) and 2 subscales, the EPDS-7 and EPDS-2, are highly accurate at identifying postpartum depression among adolescent mothers. In pediatric settings with limited time and resources, these brief scales have potential to be used as effective depression screening tools. (Read the full article)

Studies have shown dysfunction in the baroreflex mechanism and the autonomic nervous system, particularly in the sympathetic nervous system, in the pathophysiology of chronic fatigue syndrome, postural orthostatic tachycardia syndrome, and syncope.

Vitamin B₁₂ deficiency is associated with postural orthostatic tachycardia syndrome in adolescence. (Read the full article)

Preterm infants dependent on parenteral nutrition are vulnerable to deficits in early postnatal nutritional intake. This coincides with a period of suboptimal head growth. Observational studies indicate that poor nutritional intake is associated with suboptimal head growth and neurodevelopmental outcome.

This study provides randomized controlled trial evidence that head growth failure in the first 4 weeks of life can be ameliorated with early nutritional intervention. Early macronutrient intake can be enhanced by optimizing a standardized, concentrated neonatal parenteral nutrition regimen. (Read the full article)

Cognitive rest is recommended for the management of sport-related concussions. There are limited data to support this recommendation.

This study adds empirical data supporting the recommendation for cognitive rest after a sport-related concussion. (Read the full article)

Infant sleep and crying problems are common and associated with postnatal depression. No programs aiming to prevent all 3 issues have been rigorously evaluated.

A prevention program targeting these issues improves caregiver mental health, behaviors, and cognitions around infant sleep. Implementation at a population level may be best restricted to infants who are frequent feeders because they experience fewer crying and daytime sleep problems. (Read the full article)

Prenatal lipid-based nutrient supplementation has been demonstrated to increase birth length. However, the impact of this intervention on infant growth and morbidity is unknown.

Infants from mothers who were given prenatal lipid-based nutrient supplements showed decelerated linear growth. The gain in length at birth related to prenatal lipid-based nutrient supplementation was not sustained during infancy. (Read the full article)

After mild traumatic brain injury, most youth recover well. A minority of patients report persistent symptoms, which relate to both injury and noninjury factors. In adult studies, validity test performance is 1 noninjury factor that relates to persistent symptoms.

This is the first pediatric study to demonstrate that validity test failure is associated with increased symptoms after mild traumatic brain injury. The findings suggest that some symptoms conceptualized as injury-related "postconcussive" problems are better explained by exaggeration or feigning. (Read the full article)

Medical devices approved for adults can be used to treat children despite the lack of rigorous evidence. In 2007, Congress passed the Pediatric Medical Device Safety and Improvement Act to stimulate pediatric device development.

Most pediatric devices approved since the legislative change have had limited premarket study in children, with pediatric patients representing <10% of trial participants. Postmarketing studies required by the US Food and Drug Administration also yielded limited additional pediatric data. (Read the full article)

Although there has been increasing research into the effects of concussion on the developing brain in recent years, little is known about the expected duration and clinical course of individual post-concussive symptoms in children.

Children and adolescents have a significant burden of disease after concussion, with typical patients experiencing physical effects such as headache immediately after the injury, emotional symptoms later in the recovery period, and cognitive symptoms that may be present throughout. (Read the full article)

Exposure to second-hand tobacco smoke during pregnancy and infancy has been linked to development of asthma, rhinitis, and eczema in young children. It is unclear whether these risks persist into adolescence.

Exposure to second-hand smoke in utero or during infancy influences the development of allergic disease up to adolescence. Excess risks for asthma and rhinitis were seen primarily in early childhood, whereas those for eczema occurred at later ages. (Read the full article)