“Capacity”, “best interests”, “will and preferences” and the UN Convention on the Rights of Persons with Disabilities

The United Nations (UN) Convention on the Rights of Persons with Disabilities (CRPD) is the most up‐to‐date international legal instrument concerning the rights of persons with disabilities. Such persons are taken to include those with serious mental disorders. According to an authoritative interpretation of a crucial Article (Article 12 ‐ Equal recognition before the law) by the UN CRPD Committee, involuntary detention and treatment of people with mental health disabilities are prohibited under the Convention. Both conventional mental health law and “capacity‐based” law are deemed to violate the Convention. However, some other UN bodies are not in full agreement (for example, the UN Human Rights Committee and the Subcommittee on Prevention of Torture and Other Cruel, Inhuman or Degrading Treatment or Punishment), while others are less explicitly absolutist (for example, the Human Rights Council). Furthermore, strong criticisms of the position of the CRPD Committee have been mounted from a number of academic quarters. These criticisms center on whether the role of a person's ability to make a decision can be ignored, no matter the circumstances. Much of the above debate turns on the concept of “legal capacity” and the now often‐repeated precept that one must always respect the “will and preferences” of the person with a disability. However, “will and preferences” remains undefined. In this paper, I offer an analysis of “will and preferences” that can clarify interventions that may be acceptable or non‐acceptable under the terms of the UN Convention.     

Constraints on the Structure of Combinatorial “Chick-a-dee” Calls

“Chick-a-dee” calls of the black-capped chickadee (Parus atricapillus) constitute a combinatorial system of animal communication, apparently the only such system yet described. Four note-types, which may be omitted or repeated a variable number of times, occur in a fixed sequence (A–B–C–D) to constitute calls. Quantitative analyses determining the nature of departures from first-order transitional probabilities between successive notes revealed a variety of results that point consistently to two underlying features of calls. (1) Some constraint operates to limit the length of calls, as manifest in shortening of repetition-strings and omitting of note-types expected to follow. (2) There is an opposing tendency to include at least one or two D-notes at the end of a call, regardless of the overall length. The second feature suggests important semantic properties of D-notes, especially the ratio of D s to other note-types and the flock-specific acoustical structure of D-notes. The constraint on length of call does not appear intimately related to semantic causes, but may instead be determined by the maximum duration of continuous phonation, in parallel with the fundamental breath-group of human speech. In this respect, a “chick-a-dee” call resembles an entire “natural sentence” of spoken human language.     

A critique of the “ultra‐high risk” and “transition” paradigm

The transdiagnostic expression of psychotic experiences in common mental disorder (anxiety/depression/substance use disorder) is associated with a poorer prognosis, and a small minority of people may indeed develop a clinical picture that meets criteria for schizophrenia. However, it appears neither useful nor valid to observe early states of multidimensional psychopathology in young people through the “schizo”‐prism, and apply misleadingly simple, unnecessary and inefficient binary concepts of “risk” and “transition”. A review of the “ultra‐high risk” (UHR) or “clinical high risk” (CHR) literature indicates that UHR/CHR samples are highly heterogeneous and represent individuals diagnosed with common mental disorder (anxiety/depression/substance use disorder) and a degree of psychotic experiences. Epidemiological research has shown that psychotic experiences are a (possibly non‐causal) marker of the severity of multidimensional psychopathology, driving poor outcome, yet notions of “risk” and “transition” in UHR/CHR research are restrictively defined on the basis of positive psychotic phenomena alone, ignoring how baseline differences in multidimensional psychopathology may differentially impact course and outcome. The concepts of “risk” and “transition” in UHR/CHR research are measured on the same dimensional scale, yet are used to produce artificial diagnostic shifts. In fact, “transition” in UHR/CHR research occurs mainly as a function of variable sample enrichment strategies rather than the UHR/CHR “criteria” themselves. Furthermore, transition rates in UHR/CHR research are inflated as they do not exclude false positives associated with the natural fluctuation of dimensional expression of psychosis. Biological associations with “transition” thus likely represent false positive findings, as was the initial claim of strong effects of omega‐3 polyunsatured fatty acids in UHR samples. A large body of UHR/CHR intervention research has focused on the questionable outcome of “transition”, which shows lack of correlation with functional outcome. It may be more productive to consider the full range of person‐specific psychopathology in all young individuals who seek help for mental health problems, instead of “policing” youngsters for the transdiagnostic dimension of psychosis. Instead of the relatively inefficient medical high‐risk approach, a public health perspective, focusing on improved access to a low‐stigma, high‐hope, small scale and youth‐specific environment with acceptable language and interventions may represent a more useful and efficient strategy.     

Distribution of the Character States “Early Sympetaly” and “Late Sympetaly” Within the “Sympetalae Tetracyclicae” and Presumably Allied Groups*

Within the Asteridae (“Sympetalae Tetracyclicae”) two main developmental patterns can be distinguished as regards the formation of corolla tubes, namely “early” and “late sympetaly”. Since the character “ontogeny of sympetaly”, after intensive studies, proved to be valuable for systematic considerations, we now recognize two blocks of orders within the Asteridae (and related groups): the Asteridae A-block and the Asteridae B-block (Figs. 82 and 83). By and large this bipartition referring mainly to the corolla tube development corresponds well with major lineages indentified by recent molecular data (see, e.g., Chase et al., 1993). Asteridae A-block is characterized predominantely by “late sympetaly” the “early sympetaly” in Rubiales and Oleales can be interpreted as derived within this block or can be linked with that in Asteridae B-block. Asteridae B-block is uniform throughout in its “early sympetaly”. In this block it is a primitive character, as judged from its occasional occurrence in the choripetalous Cornales and Apiales (Apiaceae, Araliaceae, Pittosporaceae), which can be regarded as ancestral for block B.     

Tumor microenvironment as the “regulator” and “target” for gene therapy

In this review, we focus on strategies for designing functional nano gene carriers, as well as choosing therapeutic genes targeting the tumor microenvironment. Gene mutations have a great impact on the occurrence of cancer. Thus, gene therapy plays a major role in cancer therapy and has the potential to cure cancer. Well‐designed gene therapy largely relies on effective gene carriers, which can be divided into viral carriers and non‐viral carriers. A gene carrier delivers functional genes to their intracellular target and avoids nucleic acids being degraded by nucleases in the serum. Most conventional cancer gene therapies only target cancer cells and do not appear to be sufficintly efficient to pass clinical trials. Accumulating evidence has shown that extending the therapeutic strategies to the tumor microenvironment, rather than the tumor cell itself, can allow more options for achieving robust anti‐cancer efficiency. In addition, unusual features between tumor microenvironment and normal tissues, such as a lower pH, higher glutathione and reactive oxygen species concentrations, and overexpression of some enzymes, facilitate the design of smart stimuli‐responsive gene carriers regulated by the tumor microenvironment. These carriers interact with nucleic acids and then form stable nanoparticles under physiological conditions. By regulation of the tumor microenvironment, stimuli‐responsive gene carriers are able to change their properties and achieve high gene delivery efficiency. Considering the tumor microenvironment as the “regulator” and “target” when designing gene carriers and choosing therapeutic genes shows significant benefit with respect to improving the accuracy and efficiency of cancer gene therapy.     

Petite bodies of the “robust” australopithecines

The “robust” australopithecines are often depicted as having large and powerfully built bodies to match their massive masticatory apparatus, but until 1988 the sample of postcranial remains attributed with certainty to this group was very limited. Almost nothing was known about the body of the East African “robust” australopithecine because taxonomic attribution of the postcrania was so uncertain. The body of the South African “robust” australopithecine had to be reconstructed from about a dozen isolated fragments of postcrania. Now a partial skeleton is attributed with confidence to the East African “robust” group along with several isolated bones. The South African sample has more than tripled. Analyses of this vastly expanded sample reveal that a large portion of postcrania attributed to “robust” australopithecines from Swartkrans Member 1 (35%) are from extraordinarily small-bodied individuals similar in size to a modern Pygmy weighing as little as 28 kg. These small elements include parts from the forelimb, spine, and hindlimb. About 22% of these Swartkrans 1 “robust” australopithecines are about the same size as a modern human weighing about 43 kgs and about 43% are larger than this standard but less than or equal to a 54 kg modern human. Approximately the same pattern is true for the Swartkrans 2 hominids, but taxonomic attribution is less certain. All of the Member 3 specimens are similar in size to the 45 kg standard. The partial skeleton of the East African “robust” australopithecine (KNM-ER 1500) has hindlimb joints that would correspond to a modern human of 34 kgs although the actual weight may be 5 to 10 kgs greater judging from shaft robusticity and forelimb size. The largest postcranial element attributed with some certainty to the East African “robust” australopithecine group (the talus, KNM-ER 1464) is about the same overall size as a modern human of 54 kgs, although its tibial facet is slightly smaller. Although many previous studies have hinted at the possibility that “robust” australopithecines had relatively small bodies, the new fossils provide substantial evidence that these creatures ranged from quite small to only moderate in body size relative to modern humans. These were the petite-bodied vegetarian cousins of our ancestors. Sexual dimorphism in body size appears to be greater than that in modern humans, similar to that in Pan, and less than that in Gorilla or Pongo, although such comparisons are of limited value given the small samples, poorly known body proportions, time averaging, and many other problems.