Metformin use in pregnancy: promises and uncertainties

Metformin has been prescribed in pregnancy for over 40 years; for much of this time, use has been limited both in numbers and geographically, and the evidence base has been confined to observational studies. In early years, perceived safety concerns and lack of availability of the drug in many countries acted as a barrier to use. More recently, RCTs have begun to examine the role of metformin in pregnancy in much-needed detail. However, this evidence base has been interpreted differently in different countries, leading to very wide variation in its current application in pregnancy. In this short review, we will discuss the history of metformin in pregnancy and highlight some of the key clinical trials. We will then consider some of the remaining controversies associated with metformin use in pregnancy, most important of these being the potential for long-term ‘programming’ effects on the fetus as a result of metformin being able to cross the placenta. We will also consider clinical situations where metformin might be avoided. Finally, we will discuss some future directions for this drug as it reaches its sixtieth anniversary

Harnessing enforcement leverage at the border to minimize biological risk from international live species trade

Allocating inspection resources over a diverse set of imports to prevent entry of plant pests and pathogens presents a substantial policy design challenge. We model inspections of live plant imports and producer responses to inspections using a “state-dependent” monitoring and enforcement model. We capture exporter abatement response to a set of feasible inspection policies from the regulator. Conditional on this behavioral response, we solve the regulator’s problem of selecting the parameters for the state-dependent monitoring regime to minimize entry of infested shipments. We account for exporter heterogeneity, fixed penalties for noncompliance, imperfect abatement control and imperfect inspections at the border. Overall, we estimate that state-dependent targeting (based on historical interceptions) cuts the rate of infested shipments that are accepted by one-fifth, relative to uniformly allocated inspections

Absorption Efficiencies of Forsterite. I: DDA Explorations in Grain Shape and Size

We compute the absorption efficiency (Qabs) of forsterite using the discrete dipole approximation (DDA) in order to identify and describe what characteristics of crystal grain shape and size are important to the shape, peak location, and relative strength of spectral features in the 8-40 {\mu}m wavelength range. Using the DDSCAT code, we compute Qabs for non-spherical polyhedral grain shapes with a_eff = 0.1 {\mu}m. The shape characteristics identified are: 1) elongation/reduction along one of three crystallographic axes; 2) asymmetry, such that all three crystallographic axes are of different lengths; and 3) the presence of crystalline faces that are not parallel to a specific crystallographic axis, e.g., non-rectangular prisms and (di)pyramids. Elongation/reduction dominates the locations and shapes of spectral features near 10, 11, 16, 23.5, 27, and 33.5 {\mu}m, while asymmetry and tips are secondary shape effects. Increasing grain sizes (0.1-1.0 {\mu}m) shifts the 10, 11 {\mu}m features systematically towards longer wavelengths and relative to the 11 {\mu}m feature increases the strengths and slightly broadens the longer wavelength features. Seven spectral shape classes are established for crystallographic a-, b-, and c-axes and include columnar and platelet shapes plus non-elongated or equant grain shapes. The spectral shape classes and the effects of grain size have practical application in identifying or excluding columnar, platelet or equant forsterite grain shapes in astrophysical environs. Identification of the shape characteristics of forsterite from 8-40 {\mu}m spectra provides a potential means to probe the temperatures at which forsterite formed.Comment: 55 pages, 15 figure

Less-structured time in children's daily lives predicts self-directed executive functioning.

Executive functions (EFs) in childhood predict important life outcomes. Thus, there is great interest in attempts to improve EFs early in life. Many interventions are led by trained adults, including structured training activities in the lab, and less-structured activities implemented in schools. Such programs have yielded gains in children's externally-driven executive functioning, where they are instructed on what goal-directed actions to carry out and when. However, it is less clear how children's experiences relate to their development of self-directed executive functioning, where they must determine on their own what goal-directed actions to carry out and when. We hypothesized that time spent in less-structured activities would give children opportunities to practice self-directed executive functioning, and lead to benefits. To investigate this possibility, we collected information from parents about their 6-7 year-old children's daily, annual, and typical schedules. We categorized children's activities as "structured" or "less-structured" based on categorization schemes from prior studies on child leisure time use. We assessed children's self-directed executive functioning using a well-established verbal fluency task, in which children generate members of a category and can decide on their own when to switch from one subcategory to another. The more time that children spent in less-structured activities, the better their self-directed executive functioning. The opposite was true of structured activities, which predicted poorer self-directed executive functioning. These relationships were robust (holding across increasingly strict classifications of structured and less-structured time) and specific (time use did not predict externally-driven executive functioning). We discuss implications, caveats, and ways in which potential interpretations can be distinguished in future work, to advance an understanding of this fundamental aspect of growing up

Pathways into services for offenders with intellectual disabilities : childhood experience, diagnostic information and offence variables

The patterns and pathways into intellectual disability (ID) offender services were studied through case file review for 477 participants referred in one calendar year to community generic, community forensic, and low, medium, and maximum secure services. Data were gathered on referral source, demographic information, index behavior, prior problem behaviors, diagnostic information, and abuse or deprivation. Community referrers tended to refer to community services and secure service referrers to secure services. Physical and verbal violence were the most frequent index behaviors, whereas contact sexual offenses were more prominent in maximum security. Age at first incident varied with security, with the youngest in maximum secure services. Attention-deficit/hyperactivity disorder or conduct disorder was the most frequently recorded diagnosis, and severe deprivation was the most frequent adverse developmental experience. Fire starting, theft, and road traffic offenses did not feature prominently. Generic community services accepted a number of referrals with forensic-type behavior and had higher proportions of both women and people with moderate or severe ID

Smoothed Analysis of Tensor Decompositions

Low rank tensor decompositions are a powerful tool for learning generative models, and uniqueness results give them a significant advantage over matrix decomposition methods. However, tensors pose significant algorithmic challenges and tensors analogs of much of the matrix algebra toolkit are unlikely to exist because of hardness results. Efficient decomposition in the overcomplete case (where rank exceeds dimension) is particularly challenging. We introduce a smoothed analysis model for studying these questions and develop an efficient algorithm for tensor decomposition in the highly overcomplete case (rank polynomial in the dimension). In this setting, we show that our algorithm is robust to inverse polynomial error -- a crucial property for applications in learning since we are only allowed a polynomial number of samples. While algorithms are known for exact tensor decomposition in some overcomplete settings, our main contribution is in analyzing their stability in the framework of smoothed analysis. Our main technical contribution is to show that tensor products of perturbed vectors are linearly independent in a robust sense (i.e. the associated matrix has singular values that are at least an inverse polynomial). This key result paves the way for applying tensor methods to learning problems in the smoothed setting. In particular, we use it to obtain results for learning multi-view models and mixtures of axis-aligned Gaussians where there are many more "components" than dimensions. The assumption here is that the model is not adversarially chosen, formalized by a perturbation of model parameters. We believe this an appealing way to analyze realistic instances of learning problems, since this framework allows us to overcome many of the usual limitations of using tensor methods.Comment: 32 pages (including appendix

An ecomimicry design approach for extensive green roofs

Extensive green roofs (EGRs) have been promoted as a multifunctional urban green infrastructure (UGI) solution that can ameliorate some of the negative environmental effects associated with urbanisation and provide habitat for wildlife. To date ecological EGR research remains limited, yet studying and understanding the ecology and ecological processes of these novel urban ecosystems could maximise their potential to conserve biodiversity and deliver multiple ecosystem services to urban areas. Here we present an overview of how a novel ‘ecomimicry’ approach can be used to ensure that locally important habitats are created and restored as part of urban green infrastructure strategies, and that biodiversity is embedded at the heart of EGR design. This can help urban developments meet sustainability targets and contribute to the goal of no-net-loss of biodiversity. Conserving urban biodiversity through ecomimicry will increase opportunities for urban communities to reconnect with nature and improve the quality of life for people in cities

Investigations of excitation energy transfer and intramolecular interactions in a nitrogen corded distrylbenzene dendrimer system.

The photophysics of an amino-styrylbenzene dendrimer (A-DSB) system is probed by time-resolved and steady state luminescence spectroscopy. For two different generations of this dendrimer, steady state absorption, emission, and photoluminescence excitation spectra are reported and show that the efficiency of energy transfer from the dendrons to the core is very close to 100%. Ultrafast time-resolved fluorescence measurements at a range of excitation and detection wavelengths suggest rapid (and hence efficient) energy transfer from the dendron to the core. Ultrafast fluorescence anisotropy decay for different dendrimer generations is described in order to probe the energy migration processes. A femtosecond time-scale fluorescence depolarization was observed with the zero and second generation dendrimers. Energy transfer process from the dendrons to the core can be described by a Förster mechanism (hopping dynamics) while the interbranch interaction in A-DSB core was found to be very strong indicating the crossover to exciton dynamics

Ramsar Policy Brief No. 5. Restoring drained peatlands: A necessary step to achieve global climate goals

Peatlands cover about 400 million hectares (ha), or 3% of the land surface of our planet. Yet they store more carbon, more effectively and for longer periods, than any other ecosystem on land. Intact peatlands also provide essential ecosystem services such as regulating water cycles, purifying water, and supporting a wealth of biodiversity. Since peat is hidden below ground, it is often unrecognised and can be damaged unknowingly. New, large peatland areas are still being discovered including forest-covered peatlands in the tropics. Around 50 million ha of peatlands globally are currently drained and have been transformed to grazing land, forestry land and cropland, used for peat extraction or impacted by infrastructure. These drained peatlands are responsible for approximately 4% (2 Gt CO2 -eq/year) of all anthropogenic greenhouse gas emissions. Achieving the climate goals of the Paris Agreement requires protection of all remaining intact peatland and rapid restoration of almost all drained peatlands. This will also contribute to delivering the Sustainable Development Goals (SDGs), in particular SDG 6, Target 6.6, on protecting and restoring water related ecosystems and SDG 15, Targets 15.1, on conservation, restoration and sustainable use of terrestrial and inland freshwater ecosystems and their services, as well as 15.5 on reducing degradation of natural habitats. The United Nations Decade on Ecosystem Restoration 2021-2030 provides the opportunity to rapidly scale up efforts