The phrase "a substantial and difficult" is correct and usable in written English.
It can be used to describe something that is both significant in size or importance and challenging in nature.
Example: "The project presented a substantial and difficult challenge for the entire team."
Alternatives: "a considerable and challenging" or "a significant and tough".
With refugee flows predicted to be massive and widespread reconstruction requirements a certainty even in the unexpected event of a quick US-Iraqi success, the next president may soon face substantial and difficult decisions about Mosul in the battle's aftermath.
Regarding non-endemic vector-borne diseases, respondents noted that the impacts could be substantial and difficult to adapt to, and referred to public perception ('fright factors' and public unrest).
"But because of long standing wage and other differences what we will see is a lot more seniors forced to make substantial sacrifices and difficult choices".
This could be considered a blessing in disguise, as a storage-centric social network would have probably had a difficult time building a substantial userbase, and may have simply resulted in more lost time and money.
In light of a substantial number of initially difficult psternal long-axis and subcostal views, the PUD's most simple and immediate use may be in the rapid detection of life-threatening pulmonary edema.
Although there were some clinical similarities defined in small number of patients, such as patients with liver disease, cardiomyopathy or agenesis of the corpus callosum, there was a substantial overlap, making it difficult to form homogeneous phenotypic groups.
Before the second world war, German science had demonstrated facts which, when war erupted, became crucial: a fissionable component of natural uranium which could produce a nuclear chain reaction; the existence of a possibly fissionable element 93 or 94, and a substantial lead in a new, difficult, but potentially important aspect of civil and weapons research.
However, this would require a substantial experimental effort, and would be very difficult to prove unless fibrinogen knockout animal models for S. pyogenes nasopharyngeal colonization and invasive infections are established.
The first two years of work with tri-borough colleagues in Kensington & Chelsea and Hammersmith & Fulham show that substantial savings are achievable and difficult problems can be tackled by working in partnership with other local authorities.
Respecting a wide range of worldviews while increasing acceptance of biological evolution as the scientific explanation for the origin of species is a substantial challenge that may be difficult to achieve.
